Dolores Malaspina, M.D.

An evidence-based response to 'Genes and schizophrenia: a pseudoscientific disenfranchisement of the individual'
Rosedale M; Perrin M; Buccola N; Strauss S; Malaspina D
2012 Feb;19(1):83-84, Journal of psychiatric & mental health nursing
— id: 150612, year: 2012, vol: 19, page: 83, stat: Journal Article,

Paternal age related schizophrenia and cardiac autonomic regulation profiles
Antonius, Daniel; Kimhy, David; Harkavy-Friedman, Jill; Crystal, Sarah; Goetz, Ray; Malaspina, Dolores
2011 Apr;127(1-3):273-275, Schizophrenia research
— id: 140417, year: 2011, vol: 127, page: 273, stat: Journal Article,

PATERNAL AGE RELATED CHIZOPHRENIA (PARS): LATENT SUBGROUPS DETECTED BY K-MEANS CLUSTER ANALYSIS
Antonius, Daniel; Lee, Hyejoo; Ahn, Hongshik; Perrin, Mary; Opler, Mark; Kleinhaus, Karine; Goetz, Raymond; Tremeau, Fabien; Harlap, Susan; Malaspina, Dolores
2011 MAR ;37(6022):1-1, Schizophrenia bulletin
— id: 128813, year: 2011, vol: 37, page: 1, stat: Journal Article,

White matter integrity and lack of insight in schizophrenia and schizoaffective disorder
Antonius, Daniel; Prudent, Vasthie; Rebani, Yasmina; D'Angelo, Debra; Ardekani, Babak A; Malaspina, Dolores; Hoptman, Matthew J
2011 May;128(1-3):76-82, Schizophrenia research
OBJECTIVE: Poor insight into illness is commonly associated with schizophrenia and has implications for the clinical outcome of the disease. A better understanding of the neurobiology of these insight deficits may help the development of new treatments targeting insight. Despite the importance of this issue, the neural correlates of insight deficits in schizophrenia remain poorly understood. METHOD: Thirty-six individuals diagnosed with schizophrenia or schizoaffective disorder underwent diffusion tensor imaging (DTI). The subjects were assessed on two dimensions of insight (symptom awareness and attribution of symptoms) using the Scale to Assess Unawareness of Mental Disorder (SUMD). Level of psychosis was assessed with the Positive and Negative Syndrome Scale (PANSS). RESULTS: White matter abnormalities in the right superior frontal gyrus, left middle frontal gyrus, bilateral parahippocampal gyrus, adjacent to the right caudate head, right thalamus, left insula, left lentiform nucleus, left fusiform gyrus, bilateral posterior cingulate, left anterior cingulate, right cingulate gyrus, left lingual gyrus, and bilateral claustrum were associated with symptom unawareness. Misattribution of symptoms was related to deficits in the white matter adjacent to the right lentiform nucleus, left middle temporal gyrus, and the right precuneus. CONCLUSIONS: Impaired insight in schizophrenia implicates a complex neural circuitry: white matter deficits in fronto-temporo brain regions are linked to symptom unawareness; compromised temporal and parietal white matter regions are involved in the misattribution of symptoms. These findings suggest the multidimensional construct of insight has multiple neural determinants
— id: 131961, year: 2011, vol: 128, page: 76, stat: Journal Article,

The relationship of social function to depressive and negative symptoms in individuals at clinical high risk for psychosis
Corcoran, C M; Kimhy, D; Parrilla-Escobar, M A; Cressman, V L; Stanford, A D; Thompson, J; David, S Ben; Crumbley, A; Schobel, S; Moore, H; Malaspina, D
2011 Feb;41(2):251-261, Psychological medicine
BACKGROUND: Social dysfunction is a hallmark symptom of schizophrenia which commonly precedes the onset of psychosis. It is unclear if social symptoms in clinical high-risk patients reflect depressive symptoms or are a manifestation of negative symptoms. METHOD: We compared social function scores on the Social Adjustment Scale-Self Report between 56 young people (aged 13-27 years) at clinical high risk for psychosis and 22 healthy controls. The cases were also assessed for depressive and 'prodromal' symptoms (subthreshold positive, negative, disorganized and general symptoms). RESULTS: Poor social function was related to both depressive and negative symptoms, as well as to disorganized and general symptoms. The symptoms were highly intercorrelated but linear regression analysis demonstrated that poor social function was primarily explained by negative symptoms within this cohort, particularly in ethnic minority patients. CONCLUSIONS: Although this study demonstrated a relationship between social dysfunction and depressive symptoms in clinical high-risk cases, this association was primarily explained by the relationship of each of these to negative symptoms. In individuals at heightened risk for psychosis, affective changes may be related to a progressive decrease in social interaction and loss of reinforcement of social behaviors. These findings have relevance for potential treatment strategies for social dysfunction in schizophrenia and its risk states and predict that antidepressant drugs, cognitive behavioral therapy and/or social skills training may be effective
— id: 125620, year: 2011, vol: 41, page: 251, stat: Journal Article,

Olfactory neuroepithelium-derived neural progenitor cells as a model system for investigating the molecular mechanisms of neuropsychiatric disorders
Evgrafov, Oleg V; Wrobel, Bozena B; Kang, Xin; Simpson, George; Malaspina, Dolores; Knowles, James A
2011 Oct;21(5):217-228, Psychiatric genetics
OBJECTIVE: Most expression profiling studies of neuropsychiatric disorders have used RNA from postmortem brain tissue. Such studies are confounded by terminal events, environmental variables, such as drug use or abuse, postmortem interval, and tissue pH. To address these limitations, we have explored the use of cultured neuronal cells derived from olfactory neuroepithelium (CNON) from nasal biopsies as an alternate source of RNA. CNON cells are primarily composed of neural progenitor cells and are less influenced by environmental variables as compared with adult postmortem brain tissue. METHODS: We collected biopsy samples and established CNON cultures from eight schizophrenia cases and eight healthy comparison individuals. RNA from the cells was profiled using Affymetrix Human Exon 1.0 ST arrays and the results were validated by immunostaining and real-time quantitative PCR. RESULTS: The expression data show that CNON are primarily composed of neural progenitor cells. Furthermore, we observed a substantially higher correlation of global expression between control samples of CNON (0.98), as compared with postmortem tissue (GDS1917) (0.88). Finally, using the genome-wide expression data, we were able to differentiate CNON samples derived from individuals with and without schizophrenia in a principal component analysis and to identify candidate schizophrenia genes. CONCLUSION: CNON is a novel model system for the study of neuropsychiatric disorders that drastically reduces both technical and biological noise as compared with postmortem tissue and is therefore well suited for the identification of genes that are differentially expressed between cases and controls
— id: 139503, year: 2011, vol: 21, page: 217, stat: Journal Article,

Self-reported coping strategies in families of patients in early stages of psychotic disorder: an exploratory study
Gerson, Ruth; Wong, Celine; Davidson, Larry; Malaspina, Dolores; McGlashan, Thomas; Corcoran, Cheryl
2011 Feb;5(1):76-80, Early Intervention in Psychiatry
AIM: Coping by families of patients with schizophrenia include 'approach' strategies considered to be adaptive (e.g. reinterpretation) and potentially maladaptive 'avoidant' strategies (denial/disengagement, use of alcohol and drugs). Little is known about coping strategies used by families of individuals with incipient or emergent psychosis. METHODS: Self-reported coping styles were assessed in family members of 11 ultra high risk and 12 recent-onset psychosis patients, using a modified version of Carver's Coping Orientations to Problems Experienced questionnaire. RESULTS: Families reported moderate use of 'approach' coping (e.g. planning, seeking social support, positive reinterpretation, acceptance and turning to religion) and rare use of 'avoidant' coping strategies (denial/disengagement and use of alcohol and drugs). CONCLUSIONS: The greater endorsement of 'approach' coping by these families is consistent with findings for families of first episode psychosis patients, and it is in contrast to more prevalent 'avoidant' coping by families of patients with more chronic psychotic illness. Early intervention could plausibly help families maintain the use of potentially more adaptive 'approach' coping strategies over time
— id: 129207, year: 2011, vol: 5, page: 76, stat: Journal Article,

Multivoxel Proton MR Spectroscopy Used to Distinguish Anterior Cingulate Metabolic Abnormalities in Patients with Schizophrenia
Hardy, Caitlin J; Tal, Assaf; Babb, James S; Perry, Nissa N; Messinger, Julie W; Antonius, Daniel; Malaspina, Dolores; Gonen, Oded
2011 Nov;261(2):542-550, Radiology
Purpose: To test the hypothesis that anterior cingulate cortex (ACC) subregions in patients with schizophrenia are metabolically different from those in healthy control subjects. Materials and Methods: This institutional review board-approved study was HIPAA compliant, and all participants provided written informed consent. Twenty-two patients with schizophrenia (13 male, nine female; 39.4 years +/- 10.6 [standard deviation]) and 11 age- and sex-matched control subjects (seven male, four female; 35.5 years +/- 10.7) underwent magnetic resonance (MR) imaging and three-dimensional 3-T voxel proton MR spectroscopy to measure absolute rostral and caudal ACC N-acetylaspartate (NAA), creatine (Cr), and choline (Cho) concentrations. Exact Mann-Whitney test was used to compare patient data with control data, paired-sample Wilcoxon signed rank test was used to compare subregions within groups, and receiver operating characteristic curve analysis was used to assess sensitivity and specificity in diagnosis of schizophrenia. Results: There were no significant metabolic differences between patients and control subjects or between ACC subregions in control subjects. In patients, rostral ACC NAA and Cr concentrations were significantly lower than those in caudal ACC (6.2 mM +/- 1.3 vs 7.1 mM +/- 1.3, P < .01; 5.7 mmol/L +/- 1.4 vs 6.3 mmol/L +/- 1.6, P < .01; respectively); however, this did not hold true for Cho concentrations (1.7 mmol/L +/- 0.5 vs 1.8 mmol/L +/- 0.5). For individual differences between caudal and rostral measurements, only NAA in patients was different from that in control subjects (0.9 mmol/L +/- 1.3 vs -0.1 mmol/L +/- 0.5, P < .01), enabling prediction of schizophrenia with 68% sensitivity and 91% specificity, for a difference of more than 0.4. Conclusion: Significant differences between caudal and rostral NAA concentration are found in ACC of patients with schizophrenia but not in ACC of healthy control subjects, indicating that neuronal density or integrity differences between ACC subregions may be characteristic of the disease. (c) RSNA, 2011
— id: 139474, year: 2011, vol: 261, page: 542, stat: Journal Article,

WHAT DOES PREMORBID SOCIAL ADJUSTMENT TELL US ABOUT INDIVIDUALS WITH SCHIZOPHRENIA?
Harkavy-Friedman, Jill; Goetz, R.; Malaspina, Dolores
2011 MAR ;37(6022):17-17, Schizophrenia bulletin
— id: 128815, year: 2011, vol: 37, page: 17, stat: Journal Article,

Age, sex and first treatment of schizophrenia in a population cohort
Kleinhaus, K; Harlap, S; Perrin, M; Manor, O; Weiser, M; Lichtenberg, P; Malaspina, D
2011 Jan;45(1):136-141, Journal of psychiatric research
OBJECTIVE: Schizophrenia affects men more than women, but this may not be true at all ages. This study examines the incidence of first hospitalization for treatment of schizophrenia in each sex over different ages. METHODS: We compared the incidence of first admission for treatment in a cohort of 46,388 males and 43,680 females followed from birth until ages 29-41, using life tables and proportional hazards methods. RESULTS: Life table estimates of cumulative incidence by age 40 were 1.44% in males and 0.86% in females. For over all ages the relative risk (RR) in males was 1.6 (95% confidence limits=1.4-1.8) compared with females. Before age 17 there was no significant difference between the sexes (RR=0.86, 0.56-1.3). Excess risk in males was observed only from age 17 (RR=1.7, 1.4-1.9). There was no evidence of the incidence in females catching up with that in males, during the 30s. CONCLUSION: In this population, there was a significant change, over age, in the relative incidence of first hospitalization for schizophrenia between the sexes; the excess incidence in males first developed at age 17
— id: 119222, year: 2011, vol: 45, page: 136, stat: Journal Article,

Paternal age related schizophrenia (PARS): Latent subgroups detected by k-means clustering analysis
Lee, Hyejoo; Malaspina, Dolores; Ahn, Hongshik; Perrin, Mary; Opler, Mark G; Kleinhaus, Karine; Harlap, Susan; Goetz, Raymond; Antonius, Daniel
2011 May;128(1-3):143-149, Schizophrenia research
BACKGROUND: Paternal age related schizophrenia (PARS) has been proposed as a subgroup of schizophrenia with distinct etiology, pathophysiology and symptoms. This study uses a k-means clustering analysis approach to generate hypotheses about differences between PARS and other cases of schizophrenia. METHODS: We studied PARS (operationally defined as not having any family history of schizophrenia among first and second-degree relatives and fathers' age at birth >/=35years) in a series of schizophrenia cases recruited from a research unit. Data were available on demographic variables, symptoms (Positive and Negative Syndrome Scale; PANSS), cognitive tests (Wechsler Adult Intelligence Scale-Revised; WAIS-R) and olfaction (University of Pennsylvania Smell Identification Test; UPSIT). We conducted a series of k-means clustering analyses to identify clusters of cases containing high concentrations of PARS. RESULTS: Two analyses generated clusters with high concentrations of PARS cases. The first analysis (N=136; PARS=34) revealed a cluster containing 83% PARS cases, in which the patients showed a significant discrepancy between verbal and performance intelligence. The mean paternal and maternal ages were 41 and 33, respectively. The second analysis (N=123; PARS=30) revealed a cluster containing 71% PARS cases, of which 93% were females; the mean age of onset of psychosis, at 17.2, was significantly early. CONCLUSIONS: These results strengthen the evidence that PARS cases differ from other patients with schizophrenia. Hypothesis-generating findings suggest that features of PARS may include a discrepancy between verbal and performance intelligence, and in females, an early age of onset. These findings provide a rationale for separating these phenotypes from others in future clinical, genetic and pathophysiologic studies of schizophrenia and in considering responses to treatment
— id: 133411, year: 2011, vol: 128, page: 143, stat: Journal Article,

Olfactory processing, sex effects and heterogeneity in schizophrenia
Malaspina D; Goetz R; Keller A; Messinger JW; Bruder G; Goetz D; Opler M; Harlap S; Harkavy-Friedman J; Antonius D
2011 Dec 14;:?-? #, Schizophrenia research
INTRODUCTION: Smell identification deficits are associated with negative symptoms in schizophrenia, particularly in males. Far less information is known about the relationship of odor detection sensitivity (acuity) and negative symptoms in schizophrenia, and currently there is a dearth in sex-stratified research specifically examining odor sensitivity and smell identification. METHODS: Fifty-eight individuals with schizophrenia and 42 healthy comparison subjects were assessed on tests of odor sensitivity, smell identification and cognition. Negative symptoms were assessed with the Positive and Negative Syndrome Scale and the Schedule for the Deficit Syndrome. RESULTS: In healthy males, increased odor detection sensitivity predicted better smell identification scores. In contrast, male schizophrenia patients showed a significant inverse relationship, in which increased odor sensitivity predicted lower smell identification scores. Odor sensitivity and smell identification were unrelated in both schizophrenia and healthy females. Olfactory processing was strongly linked to negative symptoms, but the relationships differed by sex. Emotional expression deficits were related to odor detection hypersensitivity in female patients, whereas smell identification deficits predicted these emotional deficits in male cases. CONCLUSION: Sex differences in olfactory functioning were identified in healthy subjects and in schizophrenia patients. Smell identification was related to negative symptoms in males with schizophrenia, whereas odor detection sensitivity predicted these features in females. Sex differences should be considered in future analyses that employ odor stimuli for neuropsychiatric research
— id: 150613, year: 2011, vol: , page: ?, stat: Journal Article,

Specific Neurochemical Abnormalities for the Rostral Anterior Cingulate in Schizophrenia
Malaspina, Dolores; Hardy, Caitlin; Goetz, Deborah; Aurejo, Nicole; Silva, Hanna; Messinger, Julie; Antonius, Daniel; Gonen, Oded
2011 MAY 1 ;69(9):263S-263S, Biological psychiatry
— id: 133328, year: 2011, vol: 69, page: 263S, stat: Journal Article,

OLFACTION AND COGNITION IN HEALTHY SUBJECTS AND SCHIZOPHREN
Malaspina, Dolores; Keller, A.; Messinger, Julie W.; Goetz, D.; Antonius, Daniel; Harkavy-Friedman, Jill; Goetz, R.; Harlap, S.
2011 MAR ;37(6022):219-219, Schizophrenia bulletin
— id: 128825, year: 2011, vol: 37, page: 219, stat: Journal Article,

FACTOR STRUCTURE OF THE POSITIVE AND NEGATIVE SYNDROME SCALE DIFFERS BY SEX
Messinger, Julie W.; Opler, Mark; Aujero, N.; Antonius, Daniel; Goetz, R.; Malaspina, D.
2011 MAR ;37(6022):6-6, Schizophrenia bulletin
— id: 128814, year: 2011, vol: 37, page: 6, stat: Journal Article,

Avolition and expressive deficits capture negative symptom phenomenology: Implications for DSM-5 and schizophrenia research
Messinger, Julie W; Tremeau, Fabien; Antonius, Daniel; Mendelsohn, Erika; Prudent, Vasthie; Stanford, Arielle D; Malaspina, Dolores
2011 Feb;31(1):161-168, Clinical Psychology Review
The DSM-5 formulation presents an opportunity to refine the negative symptom assessments that are crucial for a schizophrenia diagnosis. This review traces the history of negative symptom constructs in neuropsychiatry from their earliest conceptualizations in the 19th century. It presents the relevant literature for distinguishing between different types of negative symptoms. Although a National Institute of Mental Health consensus initiative proposed that there are five separate negative symptom domains, our review of the individual items demonstrates no more than three negative symptom domains. Indeed, numerous factor analyses of separate negative symptom scales routinely identify only two domains: 1) expressive deficits, which include affective, linguistic and paralinguistic expressions, and 2) avolition for daily life and social activities. We propose that a focus on expressive deficits and avolition will be of optimum utility for diagnosis, treatment-considerations, and research purposes compared to other negative symptom constructs. We recommend that these two domains should be assessed as separate dimensions in the DSM-5 criteria
— id: 115271, year: 2011, vol: 31, page: 161, stat: Journal Article,

DURATION OF MARRIAGE AND RISK OF SCHIZOPHRENIA IN OFFSPRING
Opler, Mark; Messinger, Julie W.; Antonius, Daniel; Kleinhaus, K.; Abramovich, E.; Lichtenberg, P.; Malaspina, D.; Harlap, S.
2011 MAR ;37(6022):60-60, Schizophrenia bulletin
— id: 128817, year: 2011, vol: 37, page: 60, stat: Journal Article,

High-frequency prefrontal repetitive transcranial magnetic stimulation for the negative symptoms of schizophrenia: a case series
Stanford, Arielle D; Corcoran, Cheryl; Bulow, Peter; Bellovin-Weiss, Sarah; Malaspina, Dolores; Lisanby, Sarah H
2011 Mar;27(1):11-17, Journal of ECT
OBJECTIVES: : The negative symptoms of schizophrenia are difficult to treat and are predictors of poor outcome. New somatic treatments are needed to reverse these symptoms and improve function. One promising approach is repetitive transcranial magnetic stimulation (rTMS), although results to date have been mixed. This pilot study assessed higher doses of rTMS and assessed particular demographic factors that may influence treatment response. METHODS: : Five patients with schizophrenia or schizoaffective disorder enrolled to receive 20 sessions of rTMS administered with a Magstim Super Rapid device (The Magstim Company Ltd, Wales, UK). Treatment was administered at 20 Hz for 2 seconds, intertrain interval of 28 seconds, and at 100% motor threshold to the left dorsolateral prefrontal cortex in an open-label pilot study. Positive and Negative Syndrome Scale symptom assessments occurred at 2-week intervals during treatment and twice at 4-week intervals after termination. RESULTS: : Treatments were well tolerated with no adverse events. One patient withdrew from the study in the setting of medication noncompliance. Of the patients who completed treatment, 2 had reductions in positive symptoms by 9% and 26%, maintained at 1 month. A third patient had a 14% reduction in negative symptoms at week 4, and a fourth patient had a 55% reduction at week 4. Negative symptom improvement was not related to depressive or extrapyramidal symptoms, which were unchanged with treatment. CONCLUSIONS: : This pilot study of rTMS treatment for the negative symptoms of schizophrenia is promising with respect to safety and feasibility. The promising preliminary evidence for improvements in this open-label setting should be followed up with a randomized clinical trial to establish efficacy. Further work may explore the potential utility of rTMS for the otherwise largely untreatable negative symptoms, which account for so much of the morbidity of schizophrenia
— id: 124092, year: 2011, vol: 27, page: 11, stat: Journal Article,

Theory of Mind in patients at clinical high risk for psychosis
Stanford, Arielle D; Messinger, Julie; Malaspina, Dolores; Corcoran, Cheryl M
2011 Sep;131(1-3):11-17, Schizophrenia research
BACKGROUND: Patients with schizophrenia have a decreased ability to interpret the intentions of other individuals, called Theory of Mind (ToM). As capacity for ToM normally advances with brain maturation, research on ToM in individuals at heightened clinical risk for psychosis may reveal developmental differences independent of disease based differences. METHODS: We examined ToM in at clinical high risk and schizophrenia patients as well as healthy controls: 1) 63 clinical high risk (CHR) patients and 24 normal youths ascertained by a CHR program; and 2) in 13 schizophrenia cases and 14 normal adults recruited through a schizophrenia program. ToM measures included first- and second-order false belief cartoon tasks (FBT) and two 'higher order' tasks ('Strange Stories Task' (SST) and the 'Reading the Mind in the Eyes' task). In the first study, CHR patients and normal youths were also assessed for cognition, 'prodromal' symptoms and social function. RESULTS: Errors on first- and second-order false belief tasks were made primarily by patients. CHR patients and their young comparison group had equivalent performance on higher order ToM, which was not significantly different from the worse ToM performance of schizophrenia patients and the higher performance of normal adult controls. In the combined dataset from both studies, all levels of ToM were associated with IQ, controlling for age and sex. ToM bore no relation to explicit memory, prodromal symptoms, social function, or later transition to psychosis. CONCLUSIONS: Higher order ToM capacity was equally undeveloped in high risk cases and younger controls, suggesting that performance on these tasks is not fully achieved until adulthood. This study also replicates the association of IQ with ToM performance described in previous studies of schizophrenia
— id: 139504, year: 2011, vol: 131, page: 11, stat: Journal Article,

Psychiatric assessment of aggressive patients: a violent attack on a resident
Antonius, Daniel; Fuchs, Lara; Herbert, Farah; Kwon, Joe; Fried, Joanna L; Burton, Paul R S; Straka, Tara; Levin, Ze'ev; Caligor, Eve; Malaspina, Dolores
2010 Mar;167(3):253-259, American journal of psychiatry
Aggressive patients often target psychiatrists and psychiatric residents, yet most clinicians are insufficiently trained in violence risk assessment and management. Consequently, many clinicians are reluctant to diagnose and treat aggressive and assaultive features in psychiatric patients and instead focus attention on other axis I mental disorders with proven pharmacological treatment in the hope that this approach will reduce the aggressive behavior. Unclear or nonexistent reporting policies or feelings of self-blame may impede clinicians from reporting assaults, thus limiting our knowledge of the impact of, and best response to, aggression in psychiatric patients. The authors pre-sent the case of a young adult inpatient with a long history of antisocial and assaultive behavior who struck and injured a psychiatric resident. With this case in mind, the authors discuss the diagnostic complexities related to violent patients, the importance of assessing violence risk when initially evaluating a patient, and the relevance of risk assessment for treatment considerations and future management. This report illustrates common deficiencies in the prevention of violence on inpatient psychiatric units and in the reporting and response to an assault, and has implications for residency and clinician training
— id: 107929, year: 2010, vol: 167, page: 253, stat: Journal Article,

Earlier parental set bedtimes as a protective factor against depression and suicidal ideation
Gangwisch, James E; Babiss, Lindsay A; Malaspina, Dolores; Turner, J Blake; Zammit, Gary K; Posner, Kelly
2010 Jan;33(1):97-106, Sleep
STUDY OBJECTIVES: To examine the relationships between parental set bedtimes, sleep duration, and depression as a quasi-experiment to explore the potentially bidirectional relationship between short sleep duration and depression. Short sleep duration has been shown to precede depression, but this could be explained as a prodromal symptom of depression. Depression in an adolescent can affect his/her chosen bedtime, but it is less likely to affect a parent's chosen set bedtime which can establish a relatively stable upper limit that can directly affect sleep duration. DESIGN: Multivariate cross-sectional analyses of the ADD Health using logistic regression. SETTING: United States nationally representative, school-based, probability-based sample in 1994-96. PARTICIPANTS: Adolescents (n = 15,659) in grades 7 to 12. MEASUREMENTS AND RESULTS: Adolescents with parental set bedtimes of midnight or later were 24% more likely to suffer from depression (OR = 1.24, 95% CI 1.04-1.49) and 20% more likely to have suicidal ideation (1.20, 1.01-1.41) than adolescents with parental set bedtimes of 10:00 PM or earlier, after controlling for covariates. Consistent with sleep duration and perception of getting enough sleep acting as mediators, the inclusion of these variables in the multivariate models appreciably attenuated the associations for depression (1.07, 0.88-1.30) and suicidal ideation (1.09, 0.92-1.29). CONCLUSIONS: The results from this study provide new evidence to strengthen the argument that short sleep duration could play a role in the etiology of depression. Earlier parental set bedtimes could therefore be protective against adolescent depression and suicidal ideation by lengthening sleep duration
— id: 134968, year: 2010, vol: 33, page: 97, stat: Journal Article,

Short sleep duration as a risk factor for hypercholesterolemia: analyses of the National Longitudinal Study of Adolescent Health
Gangwisch, James E; Malaspina, Dolores; Babiss, Lindsay A; Opler, Mark G; Posner, Kelly; Shen, Sa; Turner, J Blake; Zammit, Gary K; Ginsberg, Henry N
2010 Jul 1;33(7):956-961, Sleep
STUDY OBJECTIVES: To explore the relationship between sleep duration in adolescence and hypercholesterolemia in young adulthood. Experimental sleep restriction has been shown to significantly increase total cholesterol and LDL cholesterol levels in women. Short sleep duration has been found in cross sectional studies to be associated with higher total cholesterol and lower HDL cholesterol levels. Sleep deprivation could increase the risk for hypercholesterolemia by increasing appetite and dietary consumption of saturated fats, decreasing motivation to engage in regular physical activity, and increasing stress and resultant catecholamine induced lipolysis. No previous published population studies have examined the longitudinal relationship between sleep duration and high cholesterol. DESIGN: Multivariate longitudinal analyses stratified by sex of the ADD Health using logistic regression. SETTING: United States nationally representative, school-based, probability-based sample. PARTICIPANTS: Adolescents (n = 14,257) in grades 7 to 12 at baseline (1994-95) and ages 18 to 26 at follow-up (2001-02). MEASUREMENTS AND RESULTS: Among females, each additional hour of sleep was associated with a significantly decreased odds of being diagnosed with high cholesterol in young adulthood (OR = 0.85, 95% CI 0.75-0.96) after controlling for covariates. Additional sleep was associated with decreased, yet not statistically significant, odds ratios for hypercholesterolemia in males (OR = 0.91, 95% CI 0.79-1.05). CONCLUSIONS: Short sleep durations in adolescent women could be a significant risk factor for high cholesterol. Interventions that lengthen sleep could potentially serve as treatments and as primary preventative measures for hypercholesterolemia
— id: 114476, year: 2010, vol: 33, page: 956, stat: Journal Article,

Insomnia and sleep duration as mediators of the relationship between depression and hypertension incidence
Gangwisch, James E; Malaspina, Dolores; Posner, Kelly; Babiss, Lindsay A; Heymsfield, Steven B; Turner, J Blake; Zammit, Gary K; Pickering, Thomas G
2010 Jan;23(1):62-69, American journal of hypertension
BACKGROUND: Depression has been found to predict the incidence of hypertension and other adverse cardiovascular events in prospective studies. Insomnia and short sleep duration, which are typical symptoms of depression, have also been shown to increase the risk for hypertension incidence. Insomnia is associated with increased activation of the hypothalamic-pituitary-adrenal axis, and short sleep duration raises average 24-h blood pressure, which over time could lead to structural adaptations that gradually reset the entire cardiovascular system to operate at an elevated pressure equilibrium. No previous published population studies have examined whether insomnia and sleep duration mediate the relationship between depression and hypertension incidence. METHODS: We conducted multivariate longitudinal (1982-1992) analyses stratified by age of the First National Health and Nutrition Examination Survey (NHANES I) (n = 4,913) using Cox proportional hazards models. RESULTS: Middle-aged subjects who suffered from depression at baseline were 44% more likely to be diagnosed with hypertension over the follow-up period after controlling for covariates (hazard ratio (HR) = 1.44, 95% confidence interval (CI) 1.15-1.80). Both short sleep duration and insomnia were also significantly associated with hypertension incidence. Consistent with insomnia and sleep duration acting as mediators of the relationship between depression and hypertension incidence, the inclusion of these variables in the multivariate models appreciably attenuated the association (HR = 1.27, 95% CI 1.00-1.61). Depression, sleep duration, and insomnia were not significantly associated with hypertension incidence in elderly subjects. CONCLUSIONS: These results suggest the hypothesis that treatment of sleep problems in middle-aged individuals suffering from depression could reduce their risk for developing hypertension, and its vascular and cardiac complications
— id: 139507, year: 2010, vol: 23, page: 62, stat: Journal Article,

Enhancing the eyes: Use of minimally invasive techniques for periorbital rejuvenation
Glaser D.A.; Patel U.
2010 ;9(8):s118-s128, Journal of drugs in dermatology : JDD
Facial beauty, specifically of the periorbital complex, is an important component of physical attractiveness and non-verbal communication, and is reflective of chronological age. In fact, eye contact is often the first, and some say the most important, form of interaction between individuals. These properties have made rejuvenation of the periorbital complex highly desirable. In the past, rejuvenating the eye meant the need for invasive surgical treatments. Although these may be necessary in advanced cases, minimally or noninvasive procedures have increasingly become first line treatment options since the advent of topical therapies and minimally invasive procedures, which include botulinum toxin, dermal filler injections, laser and chemical peels, laser skin resurfacing, microdermabrasion and intense pulsed light photorejuvenation. Here, the authors review the anatomy of the periorbital complex, the characteristics of an attractive eye, and a variety of techniques that may be used alone or in combination to achieve 'the beautiful eye.'
— id: 138400, year: 2010, vol: 9, page: s118, stat: Journal Article,

Neuronal generator patterns of olfactory event-related brain potentials in schizophrenia
Kayser, Jurgen; Tenke, Craig E; Malaspina, Dolores; Kroppmann, Christopher J; Schaller, Jennifer D; Deptula, Andrew; Gates, Nathan A; Harkavy-Friedman, Jill M; Gil, Roberto; Bruder, Gerard E
2010 Nov;47(6):1075-1086, Psychophysiology
To better characterize neurophysiologic processes underlying olfactory dysfunction in schizophrenia, nose-referenced 30-channel electroencephalogram was recorded from 32 patients and 35 healthy adults (18 and 18 male) during detection of hydrogen sulfide (constant-flow olfactometer, 200 ms unirhinal exposure). Event-related potentials (ERPs) were transformed to reference-free current source density (CSD) waveforms and analyzed by unrestricted Varimax-PCA. Participants indicated when they perceived a high (10 ppm) or low (50% dilution) odor concentration. Patients and controls did not differ in detection of high (23% misses) and low (43%) intensities and also had similar olfactory ERP waveforms. CSDs showed a greater bilateral frontotemporal N1 sink (305 ms) and mid-parietal P2 source (630 ms) for high than low intensities. N1 sink and P2 source were markedly reduced in patients for high intensity stimuli, providing further neurophysiological evidence of olfactory dysfunction in schizophrenia
— id: 114195, year: 2010, vol: 47, page: 1075, stat: Journal Article,

Concurrent measurement of "real-world" stress and arousal in individuals with psychosis: assessing the feasibility and validity of a novel methodology
Kimhy, David; Delespaul, Philippe; Ahn, Hongshik; Cai, Shengnan; Shikhman, Marina; Lieberman, Jeffrey A; Malaspina, Dolores; Sloan, Richard P
2010 Nov;36(6):1131-1139, Schizophrenia bulletin
BACKGROUND: Psychosis has been repeatedly suggested to be affected by increases in stress and arousal. However, there is a dearth of evidence supporting the temporal link between stress, arousal, and psychosis during 'real-world' functioning. This paucity of evidence may stem from limitations of current research methodologies. Our aim is to the test the feasibility and validity of a novel methodology designed to measure concurrent stress and arousal in individuals with psychosis during 'real-world' daily functioning. METHOD: Twenty patients with psychosis completed a 36-hour ambulatory assessment of stress and arousal. We used experience sampling method with palm computers to assess stress (10 times per day, 10 AM --> 10 PM) along with concurrent ambulatory measurement of cardiac autonomic regulation using a Holter monitor. The clocks of the palm computer and Holter monitor were synchronized, allowing the temporal linking of the stress and arousal data. We used power spectral analysis to determine the parasympathetic contributions to autonomic regulation and sympathovagal balance during 5 minutes before and after each experience sample. RESULTS: Patients completed 79% of the experience samples (75% with a valid concurrent arousal data). Momentary increases in stress had inverse correlation with concurrent parasympathetic activity (rho = -.27, P < .0001) and positive correlation with sympathovagal balance (rho = .19, P = .0008). Stress and heart rate were not significantly related (rho = -.05, P = .3875). CONCLUSION: The findings support the feasibility and validity of our methodology in individuals with psychosis. The methodology offers a novel way to study in high time resolution the concurrent, 'real-world' interactions between stress, arousal, and psychosis. The authors discuss the methodology's potential applications and future research directions
— id: 139505, year: 2010, vol: 36, page: 1131, stat: Journal Article,

Catatonic Schizophrenia: A Cohort Prospective Study
Kleinhaus K; Harlap S; Perrin MC; Manor O; Weiser M; Harkavy-Friedman JM; Lichtenberg P; Malaspina D
2010 Aug 6;:?-?, Schizophrenia bulletin
Background: In the 20th century, catatonia was usually deemed a subtype of schizophrenia. Recently, the nature and classification of catatonia are being reconsidered. This study is the first to describe catatonia using prospectively collected data and to examine how catatonic schizophrenia differs from, or resembles, other types of schizophrenia. Methods: Data were analyzed in a cohort of 90 079 offspring followed from birth till ages 29-41 years. Proportional hazards models were used, calculating time to first psychiatric hospital admission, to compare risk factors for catatonic schizophrenia vs 'other schizophrenia.' Results: Of 568 cases of schizophrenia, 43 (7.6%) had catatonic schizophrenia. The sexes were equally at risk for catatonic schizophrenia in contrast to other schizophrenia, for which the incidence was higher in males (1.70, 1.42-2.03, P < .0001). Advancing paternal age had no influence on the risk of catatonic schizophrenia in contrast to other schizophrenia, in which the risk to offspring of fathers age 35+ was 1.27 (1.03-1.57, P = .03) compared with those of younger fathers. Those with catatonic schizophrenia were somewhat more likely to have older mothers (aged 35+) (relative risk = 2.14, 0.85-5.54) while maternal age was not related to other schizophrenia. Both were equally affected by parental history of schizophrenia. Patients with catatonia were significantly more likely to attempt suicide (P = .006). Conclusion: Patients with catatonic schizophrenia show a somewhat different profile of risk factors from those with other types of schizophrenia in this cohort and are more likely to attempt suicide. This lends some support to the hypothesis that catatonic schizophrenia may have a distinct etiology
— id: 139506, year: 2010, vol: , page: ?, stat: Journal Article,

Effects of excessive glucocorticoid receptor stimulation during early gestation on psychomotor and social behavior in the rat
Kleinhaus, Karine; Steinfeld, Sara; Balaban, Jordan; Goodman, Leora; Craft, Tara S; Malaspina, Dolores; Myers, Michael M; Moore, Holly
2010 Mar;52(2):121-132, Developmental psychobiology
Severe psychological stress in the first trimester of pregnancy increases the risk of schizophrenia in the offspring. To begin to investigate the role of glucocorticoid receptors in this association, we determined the effects of the glucocorticoid dexamethasone (2 mg/kg), administered to pregnant rats on gestation days 6-8, on maternal behaviors and schizophrenia-relevant behaviors in the offspring. Dams receiving dexamethasone exhibited increased milk ejection bouts during nursing. Offspring of dexamethasone-treated dams (DEX) showed decreased juvenile social play and a blunted acoustic startle reflex in adolescence and adulthood, effects that were predicted by frequency of milk ejections in the dams. DEX offspring also showed increased prepulse inhibition of startle and reduced amphetamine-induced motor activity, effects not correlated with maternal behavior. It is postulated that over-stimulation of receptors targeted by glucocorticoids in the placenta or other maternal tissues during early gestation can lead to psychomotor and social behavioral deficits in the offspring. Moreover, some of these deficits may be mediated by alterations in postnatal maternal behavior and physiology produced by early gestational exposure to excess glucocorticoids. (c) 2010 Wiley Periodicals, Inc. Dev Psychobiol 52:121-132, 2010
— id: 107772, year: 2010, vol: 52, page: 121, stat: Journal Article,

Epidemiological and genetic aspects of neuropsychiatric disorders
Malaspina, Dolores; Corcoran, Cheryl; Schobel, Scott; Hamilton, Steven P
Essentials of neuropsychiatry and behavioral neurosciences Arlington, VA, US: American Psychiatric Publishing, Inc.; US, 2010,
(from the chapter) The last decade has witnessed a revolution in our understanding of the etiology of many neuropsychiatric disorders. Advances in statistical genetics, genetic epidemiology, and molecular biology have provided new insights and avenues for conducting genetic and epidemiological studies and for analyzing gene-environment interactions. The recent sequencing of the human genome now sets the stage for even greater progress in the coming years. In this chapter, we first focus on the methods of genetic epidemiology and then review some of the recent findings of these disciplines in the study of neuropsychiatric disorders.
— id: 5344, year: 2010, vol: , page: 95, stat: Chapter,

Time-to-pregnancy and risk of schizophrenia
Opler, Mark G A; Harlap, Susan; Ornstein, Katherine; Kleinhaus, Karine; Perrin, Mary; Gangwisch, James E; Lichtenberg, Pesach; Draiman, Benjamin; Malaspina, Dolores
2010 May;118(1-3):76-80, Schizophrenia research
Schizophrenia has been linked to advanced paternal age, but the explanation is unknown. We questioned whether the incidence of schizophrenia would be related to male reproductive capacity, as reflected in the time taken to conceive. We measured the incidence of schizophrenia in relation to time to conception in a sub-group of 12,269 in the Jerusalem cohort whose mothers, interviewed post-partum, reported that the pregnancy had been intended. Compared with those conceived in less than 3 months, the unadjusted relative risks (RR) of schizophrenia associated with conception-waits of 3-5, 6-11 and 12+ months were 1.10 (95% confidence interval, 0.62-1.94), 1.41 (0.79-2.52) and 1.88 (1.05-3.37) with p for trend=0.035. This trend was attenuated somewhat by adjusting for paternal age, and was observed more strongly in offspring of fathers aged 30+ (p=.010). These findings suggest that factors associated with fecundability, either male or female, may contribute to the risk of schizophrenia
— id: 109205, year: 2010, vol: 118, page: 76, stat: Journal Article,

Older paternal age strongly increases the morbidity for schizophrenia in sisters of affected females
Perrin, Mary; Harlap, Susan; Kleinhaus, Karine; Lichtenberg, Pesach; Manor, Orly; Draiman, Benjamin; Fennig, Shmuel; Malaspina, Dolores
2010 Oct 5;153B(7):1329-1335, American journal of medical genetics. Part B, Neuropsychiatric genetics
The effect of a family history of schizophrenia on the risk for this disorder in the offspring has rarely been examined in a prospective population cohort accounting for the sex of the proband and the first-degree relatives, and certainly not with respect to later paternal age. The influence of affected relatives on offspring risk of schizophrenia was estimated using Cox proportional hazards regression in models that accounted for sex, relation of affected first degree relatives and paternal age in the prospective population-based cohort of the Jerusalem Perinatal Schizophrenia Study. Of all first-degree relatives, an affected mother conferred the highest risk to male and female offspring among the cases with paternal age <35 years, however, female offspring of fathers >/=35 years with an affected sister had the highest risk (RR = 8.8; 95% CI = 3.9-19.8). The risk seen between sisters of older fathers was fourfold greater than the risk to sisters of affected females of younger fathers (RR = 2.2, 95% CI 0.7-6.7). The test for interaction was significant (P = 0.03). By contrast, the risk of schizophrenia to brothers of affected males was only doubled between older (RR = 3.3, 95% 1.6-6.6) and younger fathers (RR = 1.6, 95% CI 0.7-3.5). The most striking finding from this study was the very large increase in risk of schizophrenia to sisters of affected females born to older fathers. The authors speculate that the hypothesized paternally expressed genes on the X chromosome might play some role in these observations
— id: 133892, year: 2010, vol: 153B, page: 1329, stat: Journal Article,

Critical periods and the developmental origins of disease: an epigenetic perspective of schizophrenia
Perrin, Mary; Kleinhaus, Karine; Messinger, Julie; Malaspina, Dolores
2010 Sep;1204 Suppl:E8-13, Annals of the New York Academy of Sciences
Epigenetics holds promise to explain some puzzles concerning the risk and course of psychiatric disorders. Epigenetic information is essential as a set of operating instructions for the genome, which is heritable with DNA. The epigenetic regulation of gene expression can plausibly be influenced by the environment of one's ancestors, prenatal exposures, and by early life events. Some epigenetic mechanisms may alter neurophysiology throughout life by programming gene expression, perhaps in anticipation of certain life experiences. These epigenetic signals are only meta-stable and may be perturbed by stochastic events, errors, or by environmental toxins. This introduction considers the possibility that epigenetic change that may occur as paternal age advances or during fetal adversity may be causally related to the susceptibility for schizophrenia
— id: 113661, year: 2010, vol: 1204 Suppl, page: E8, stat: Journal Article,

Human hippocampal subfields in young adults at 7.0 T: feasibility of imaging
Prudent, Vasthie; Kumar, Arun; Liu, Songtao; Wiggins, Graham; Malaspina, Dolores; Gonen, Oded
2010 Mar;254(3):900-906, Radiology
Purpose: To establish an imaging approach to visualize the 100-mum-thick hippocampal neuron-generating dentate granule cell layer (DGCL) consistently within a clinically feasible magnetic resonance (MR) imaging duration and to assess its sensitivity by quantifying the likelihood that it will be detected in healthy young adults. Materials and Methods: The study was HIPAA compliant and institutional review board approved. All subjects provided written informed consent. Ten healthy volunteers (five male subjects, five female subjects; mean age, 26 years +/- 6 [standard deviation]) were imaged at 7.0 T by using a 24-element head coil array with three-dimensional T1-weighted MR imaging for anatomic reference, followed by T2*-weighted gradient-echo (echo time, 25 msec; repetition time, 944 msec) imaging at 232-mum in-plane resolution (0.05-mm(3) pixels) in coronal and sagittal slabs (17 sections at 1 mm thick) over the hippocampus in 14 minutes. The entire study took 45 minutes. Results: The DGCL was consistently visible in all 10 enrolled subjects. All larger subfields were visible in excellent detail and contrast in every subject. Conclusion: The spatial resolution and tissue contrast at high field strength (7.0 T) MR imaging can be used to consistently reveal hippocampal morphology down to 100-mum subfields within a clinically acceptable imaging duration. This imaging technique might be used to detect cellular disarray and degenerative changes in this sensitive circuit earlier than at 1.5 T or even 3.0 T. (c) RSNA, 2010
— id: 107378, year: 2010, vol: 254, page: 900, stat: Journal Article,

Later paternal age and sex differences in schizophrenia symptoms
Rosenfield, Paul J; Kleinhaus, Karine; Opler, Mark; Perrin, Mary; Learned, Nicole; Goetz, Raymond; Stanford, Arielle; Messinger, Julie; Harkavy-Friedman, Jill; Malaspina, Dolores
2010 Feb;116(2-3):191-195, Schizophrenia research
OBJECTIVE: Advanced paternal age is consistently associated with an increased risk for schizophrenia, accounting for up to a quarter of cases in some populations. If paternal age-related schizophrenia (PARS) involves a distinct etiopathology, then PARS cases may show specific characteristics, vis-a-vis other schizophrenia cases. This study examined if PARS exhibits the symptom profile and sex differences that are consistently observed for schizophrenia in general, wherein males have an earlier onset age and more severe negative symptoms than females. METHOD: Symptoms were assessed at baseline (admission) and during medication-free and treatment phases for 153 inpatients on a schizophrenia research unit, 38 of whom fulfilled operationally defined criteria for PARS (sporadic cases with paternal age > or = 35). RESULTS: Males and females with PARS had the same age at onset and a similar preponderance of negative symptoms, whereas the other (non-PARS) cases showed the typical earlier onset age and more severe negative symptoms in males. When medications were withdrawn, PARS cases showed significantly worse symptoms than non-PARS cases (higher total PANSS scores and positive, activation, and autistic preoccupation scores). However these symptoms globally improved with antipsychotic treatment, such that the differences between the PARS and other schizophrenia cases receded. CONCLUSION: The lack of sex differences in the age at onset and the greater severity of medication-free symptoms bolster the hypothesis that PARS has a distinct etiopathology. It also suggests that female sex does not exert a protective effect on the course of PARS, as it may in other forms of schizophrenia
— id: 114478, year: 2010, vol: 116, page: 191, stat: Journal Article,

Anticipated, on-line and remembered positive experience in schizophrenia
Tremeau, Fabien; Antonius, Daniel; Cacioppo, John T; Ziwich, Rachel; Butler, Pamela; Malaspina, Dolores; Javitt, Daniel C
2010 Sep;122(1-3):199-205, Schizophrenia research
BACKGROUND: Three temporal stages in the evaluation of positive affect can be identified: anticipation, experience (hedonia) and memory. In schizophrenia, despite research indicating non-impaired hedonic capacities, little is known about anticipation and memory of positive affect. Moreover, the role of positive affect evaluations on motivation has rarely been studied in schizophrenia. METHOD: Seventy individuals with schizophrenia and 35 non-patient control participants completed an evocative emotional task consisting of pictures and sounds. Following each presentation, participants rated their hedonic experience. Ratings of pre-test anticipated and post-test remembered pleasures were also obtained. Finally, explicit motivation to repeat the task was assessed. RESULTS: Compared to control participants, schizophrenia participants demonstrated similar levels of anticipation, hedonia and motivation, as well as significantly increased remembered pleasure. In schizophrenia, affective processes had lower correlations with motivation than in controls, and only remembered pleasure predicted motivation. Moreover, the predictive value of hedonia was significantly lower in schizophrenia. CONCLUSIONS: The affective and cognitive processes involved in the anticipation, experience and memory of positive affective events showed no deficit, and to the contrary, immediately remembered pleasure was higher in schizophrenia. However, important deficits resided in the inter-connectivity between affective evaluations and motivational processes. The major deficit in schizophrenia participants' reward system was not in hedonic experiences but in the translation of pleasurable experiences into motivational states
— id: 138385, year: 2010, vol: 122, page: 199, stat: Journal Article,

Family history of affective illness in schizophrenia patients: symptoms and cognition
Anglin, Deidre; Stanford, Arielle D; Harkavy-Friedman, Jill M; Goetz, Raymond; Rosenfield, Paul; Malaspina, Dolores
2009 May;110(1-3):24-27, Schizophrenia research
This study examined the relationship between having a family history of affective disorder and neuropsychological functioning and PANSS symptoms in schizophrenia patients falling into four exclusive family history groups (affective spectrum disorders, schizophrenia spectrum disorders, both, or neither). Schizophrenia patients with a family history of affective illness had the best performance on IQ tests and executive function measures. Symptoms showed fewer family history group differences. Schizophrenia patients with a family history of affective disorder may be a distinct subtype in the group of schizophrenias and may be biologically more similar to patients with serious affective disorder
— id: 133677, year: 2009, vol: 110, page: 24, stat: Journal Article,

AROUSAL EXPERIENCE IN SCHIZOPHRENIA: SUBJECTIVE AND PHYSIOLOGICAL ASSOCIATIONS
Antonius, D; Malaspina, D; Tremeau, F; Nolan, KA
2009 MAR ;35(1-3):53-54, Schizophrenia bulletin
— id: 97763, year: 2009, vol: 35, page: 53, stat: Journal Article,

White Matter Integrity of Insight Deficits in Schizophrenia
Antonius, D; Prudent, V; Malaspina, D; D'Angel, D; Mauro, C; Catalano, D; Hoptman, MJ
2009 APR 15 ;65(8):186S-186S, Biological psychiatry
— id: 97979, year: 2009, vol: 65, page: 186S, stat: Journal Article,

Effect of socioeconomic status and parents' education at birth on risk of schizophrenia in offspring
Corcoran, Cheryl; Perrin, Mary; Harlap, Susan; Deutsch, Lisa; Fennig, Shmuel; Manor, Orly; Nahon, Daniella; Kimhy, David; Malaspina, Dolores; Susser, Ezra
2009 Apr;44(4):265-271, Social psychiatry & psychiatric epidemiology
Although it is known that schizophrenia is associated with social class, controversy exists as to the nature of this association. The authors studied the incidence of schizophrenia in relation to social class at birth in a population-based cohort of 88,829 offspring born in Jerusalem in 1964-1976. They constructed a six-point scale to index social class, based on paternal occupation at the time of birth, with each of 108 occupations being ranked by mean education. Cox proportional hazards methods were used in adjusting for sex, parents' ages, duration of marriage and birth order. Linkage with Israel's Psychiatric Registry identified 637 people admitted to psychiatric care facilities with schizophrenia-related diagnoses, before 1998. There was no gradient of risk for schizophrenia associated with social class at birth; however, offspring of fathers in the lowest social class showed a modest increase in risk (adjusted Relative Risk = 1.4; 95% Confidence interval = 1.1-1.8, P = 0.002). These data suggest that in contrast to many other health outcomes, there is not a continuous gradient for increasing schizophrenia with decreasing social class of origin. Instead, a modest increase in risk for schizophrenia was observed only for those born at the bottom of the social ladder
— id: 95337, year: 2009, vol: 44, page: 265, stat: Journal Article,

Incidence of Schizophrenia Among Second-Generation Immigrants in the Jerusalem Perinatal Cohort
Corcoran, Cheryl; Perrin, Mary; Harlap, Susan; Deutsch, Lisa; Fennig, Shmuel; Manor, Orly; Nahon, Daniella; Kimhy, David; Malaspina, Dolores; Susser, Ezra
2009 May;35(3):596-602, Schizophrenia bulletin
Objective: Increased incidence of schizophrenia is observed among some immigrant groups in Europe, with the offspring of immigrants, ie 'second-generation' immigrants particularly vulnerable. Few contemporary studies have evaluated the risk of schizophrenia among second-generation immigrants in other parts of the world. Methods: We studied the incidence of schizophrenia in relation to parental immigrant status in a population-based cohort of 88 829 offspring born in Jerusalem in 1964-1976. Parental countries of birth were obtained from birth certificates and grouped together as (1) Israel, (2) Other West Asia, (3) North Africa, and (4) Europe and industrialized countries. Cox proportional hazards methods were used in adjusting for sex, parents' ages, maternal education, social class, and birth order. Results: Linkage with Israel's Psychiatric Registry identified 637 people admitted to psychiatric care facilities with schizophrenia-related diagnoses, before 1998. Incidence of schizophrenia was not increased among second-generation immigrants in this birth cohort, neither overall nor by specific group. Conclusions: The difference in risk of schizophrenia among second-generation immigrants in Europe and in this Israeli birth cohort suggests that the nature of the immigration experience may be relevant to risk, including reasons for migration, the nature of entry, and subsequent position in the host country for immigrants and their offspring. Minority status may be of importance as, in later studies, immigrants to Israel from Ethiopia had increased risk of schizophrenia
— id: 80337, year: 2009, vol: 35, page: 596, stat: Journal Article,

Schizophrenia and birthplace of paternal and maternal grandfather in the Jerusalem perinatal cohort prospective study
Harlap, S; Perrin, M C; Deutsch, L; Kleinhaus, K; Fennig, S; Nahon, D; Teitelbaum, A; Friedlander, Y; Malaspina, D
2009 Jun;111(1-3):23-31, Schizophrenia research
Some forms of epigenetic abnormalities transmitted to offspring are manifested in differences in disease incidence that depend on parent-of-origin. To explore whether such phenomena might operate in schizophrenia spectrum disorders, we estimated the relative incidence of these conditions in relation to parent-of-origin by considering the two grandfathers' countries of birth. In a prospective cohort of 88,829 offspring, born in Jerusalem in 1964-76 we identified 637 cases through Israel's psychiatric registry. Relative risks (RR) were estimated for paternal and maternal grandfathers' countries of birth using proportional hazards methods, controlling for parents' ages, low social class and duration of marriage. After adjusting for multiple observations, we found no significant differences between descendants of maternal or paternal grandfathers born in Iraq, Iran, Turkey, Syria, Yemen, Morocco, Algeria, Tunisia, Libya/Egypt, Poland, USSR, Czechoslovakia, Germany or the USA. Those with paternal grandfathers from Romania (RR=1.9, 95% CI=1.3-2.8) or Hungary (1.6, 1.0-2.6) showed an increased incidence; however, those with maternal grandfathers from these countries experienced reduced incidence (RR=0.5, 0.3-0.8 and 0.4, 0.2-0.8). In post-hoc analyses we found that results were similar whether the comparison groups were restricted to descendants of other Europeans or included those from Western Asia and North Africa; and effects of paternal grandfathers from Romania/Hungary were more pronounced in females, while effects of maternal grandfathers from these countries were similar in males and females. These post-hoc 'hypothesis-generating' findings lead one to question whether some families with ancestors in Romania or Hungary might carry a variant or mutation at a parentally imprinted locus that is altering susceptibility to schizophrenia. Such a locus, if it exists, might involve the X chromosome
— id: 98896, year: 2009, vol: 111, page: 23, stat: Journal Article,

Amygdalofrontal Functional Disconnectivity and Reactive Aggression in Schizophrenia
Hoptman, MJ; Antonius, D; D'Angelo, D; Catalano, D; Mauro, CJ; Malaspina, D; Milham, MP
2009 APR 15 ;65(8):187S-187S, Biological psychiatry
— id: 97980, year: 2009, vol: 65, page: 187S, stat: Journal Article,

AFFECT IN SCHIZOPHRENIA: IMPLICATIONS FOR DSM V AND RESEARCH
Malaspina, D; Messinger, JW; Prudent, V; Mendelsohn, E; Antonius, D
2009 MAR ;35(1-3):3-3, Schizophrenia bulletin
— id: 97760, year: 2009, vol: 35, page: 3, stat: Journal Article,

Limbic dysregulation is associated with lowered heart rate variability and increased trait anxiety in healthy adults
Mujica-Parodi, Lilianne R; Korgaonkar, Mayuresh; Ravindranath, Bosky; Greenberg, Tsafrir; Tomasi, Dardo; Wagshul, Mark; Ardekani, Babak; Guilfoyle, David; Khan, Shilpi; Zhong, Yuru; Chon, Ki; Malaspina, Dolores
2009 Jan;30(1):47-58, Human brain mapping
OBJECTIVES:: We tested whether dynamic interaction between limbic regions supports a control systems model of excitatory and inhibitory components of a negative feedback loop, and whether dysregulation of those dynamics might correlate with trait differences in anxiety and their cardiac characteristics among healthy adults. EXPERIMENTAL DESIGN:: Sixty-five subjects received fMRI scans while passively viewing angry, fearful, happy, and neutral facial stimuli. Subjects also completed a trait anxiety inventory, and were monitored using ambulatory wake ECG. The ECG data were analyzed for heart rate variability, a measure of autonomic regulation. The fMRI data were analyzed with respect to six limbic regions (bilateral amygdala, bilateral hippocampus, Brodmann Areas 9, 45) using limbic time-series cross-correlations, maximum BOLD amplitude, and BOLD amplitude at each point in the time-series. PRINCIPAL OBSERVATIONS:: Diminished coupling between limbic time-series in response to the neutral, fearful, and happy faces was associated with greater trait anxiety, greater sympathetic activation, and lowered heart rate variability. Individuals with greater levels of trait anxiety showed delayed activation of Brodmann Area 45 in response to the fearful and happy faces, and lowered Brodmann Area 45 activation with prolonged left amygdala activation in response to the neutral faces. CONCLUSIONS:: The dynamics support limbic regulation as a control system, in which dysregulation, as assessed by diminished coupling between limbic time-series, is associated with increased trait anxiety and excitatory autonomic outputs. Trait-anxious individuals showed delayed inhibitory activation in response to overt-affect stimuli and diminished inhibitory activation with delayed extinction of excitatory activation in response to ambiguous-affect stimuli. Hum Brain Mapp 2007. (c) 2007 Wiley-Liss, Inc
— id: 80977, year: 2009, vol: 30, page: 47, stat: Journal Article,

TIME-TO-PREGNANCY AND RISK OF SCHIZOPHRENIA IN OFFSPRING
Opler, MG; Ornstein, K; Perrin, M; Kleinhaus, K; Harlap, S; Malaspina, D
2009 MAR ;35(1-3):64-64, Schizophrenia bulletin
— id: 97764, year: 2009, vol: 35, page: 64, stat: Journal Article,

The Structure of the Lived Experience for Persons Having Undergone rTMS for Depression Treatment
Rosedale, Mary; Lisanby, Sarah H; Malaspina, Dolores
2009 Oct;15(5):333-337, Journal of the American Psychiatric Nurses Association
OBJECTIVE: This phenomenological research study reports preliminary findings about experiences of persons undergoing repeated transcranial magnetic stimulation (rTMS) for depression treatment. METHODS: Giorgi's phenomenology was the method used to describe the structure of the lived experience for persons having undergone rTMS treatment for depression. Participants were recruited from the OPT-TMS pivotal depression study that resulted in the October 2008 FDA approval of rTMS. Thus far, nine persons comprise the purposive sample. Each participant was asked to describe the experience of undergoing rTMS for depression treatment and encouraged to provide as much details as possible. RESULTS: Four preliminary themes emerged to describe participants' experiences of rTMS for depression treatment: (a) a narrative of frustration and helplessness with medication treatment resistance, (b) the sensory experience of rTMS, (c) mindfulness- an enhanced awareness of the content of consciousness, and (d) the importance of connection with clinicians. CONCLUSIONS: Preliminary results of this phenomenological study make the struggle of persons with treatment-resistant depression more visible and should assist clinicians to understand how rTMS is experienced by depressed persons undergoing treatment. Moreover, results shed new light on the changes participants observe and describe with rTMS and the high value they place on a therapeutic relationship with clinicians administering treatment
— id: 139508, year: 2009, vol: 15, page: 333, stat: Journal Article,

Anterior hippocampal and orbitofrontal cortical structural brain abnormalities in association with cognitive deficits in schizophrenia
Schobel, Scott A; Kelly, Meredith A; Corcoran, Cheryl M; Van Heertum, Kristin; Seckinger, Regine; Goetz, Ray; Harkavy-Friedman, Jill; Malaspina, Dolores
2009 Oct;114(1-3):110-118, Schizophrenia research
OBJECTIVE: Numerous studies have implicated the hippocampus and prefrontal cortex in schizophrenia. However, precisely which subregions of the hippocampus and prefrontal cortex are abnormal remain unknown. Our study goal was to investigate the structure of the anterior hippocampus, posterior hippocampus, dorsolateral prefrontal cortex (DLPFC), and orbitofrontal cortex (OFC) simultaneously in thirty-eight patients with schizophrenia and twenty-nine controls to determine which of these subregions are abnormal in schizophrenia. As an exploratory study goal, we investigated the relation of neurocognition to brain structure in schizophrenia patients. METHOD: We generated detailed structural magnetic resonance imaging data and compared hippocampal and prefrontal subregional structural brain volumes between schizophrenia and control groups. We obtained a neurocognitive test battery in schizophrenia patients and studied the association of abnormal brain structures to neurocognition. RESULTS: Structural brain abnormalities were pinpointed to the left anterior hippocampus and left OFC in schizophrenia patients, which were both significantly reduced in volume. The DLPFC and posterior hippocampus, though numerically decreased in volume, were not significantly decreased. Anterior hippocampal volumes were more strongly associated with OFC volumes in schizophrenia patients compared to controls. By contrast, DLPFC volume was unrelated to anterior or posterior hippocampal volume. Both the anterior hippocampus and OFC were independently related to cognitive abnormalities common in schizophrenia, including indices of verbal, language, and executive functions. The DLPFC and posterior hippocampal volumes were unrelated to cognitive measures. CONCLUSIONS: These findings highlight related abnormalities of the anterior hippocampus and OFC in schizophrenia, which may shed light on the pathophysiology of the disorder
— id: 139509, year: 2009, vol: 114, page: 110, stat: Journal Article,

Differential targeting of the CA1 subfield of the hippocampal formation by schizophrenia and related psychotic disorders
Schobel, Scott A; Lewandowski, Nicole M; Corcoran, Cheryl M; Moore, Holly; Brown, Truman; Malaspina, Dolores; Small, Scott A
2009 Sep;66(9):938-946, Archives of general psychiatry
CONTEXT: Because schizophrenia and related disorders have a chronic time course and subtle histopathology, it is difficult to identify which brain regions are differentially targeted. OBJECTIVE: To identify brain sites differentially targeted by schizophrenia, we applied a high-resolution variant of functional magnetic resonance imaging to clinically characterized patients and matched healthy controls and to a cohort of prodromal subjects who were prospectively followed up. Additionally, to explore the potential confound of medication use, the fMRI variant was applied to rodents receiving an antipsychotic agent. DESIGN: Cross-sectional and prospective cohort designs. SETTING: Hospital clinic and magnetic resonance imaging laboratory. PARTICIPANTS: Eighteen patients with schizophrenia, 18 controls comparable in age and sex, and 18 prodromal patients followed up prospectively for 2 years. Ten C57-B mice received an antipsychotic agent or vehicle control. MAIN OUTCOME MEASURES: Regional cerebral blood volume (CBV), as measured with magnetic resonance imaging, and symptom severity, as measured with clinical rating scales. RESULTS: In a first between-group analysis that compared patients with schizophrenia with controls, results revealed abnormal CBV increases in the CA1 subfield and the orbitofrontal cortex and abnormal CBV decreases in the dorsolateral prefrontal cortex. In a second longitudinal analysis, baseline CBV abnormalities in the CA1 subfield differentially predicted clinical progression to psychosis from a prodromal state. In a third correlational analysis, CBV levels in the CA1 subfield differentially correlated with clinical symptoms of psychosis. Finally, additional analyses of the human data set and imaging studies in mice suggested that antipsychotic agents were not confounding the primary findings. CONCLUSIONS: Taken as a whole, the results suggest that the CA1 subfield of the hippocampal subregion is differentially targeted by schizophrenia and related psychotic disorders. Interpreted in the context of previous studies, these findings inform underlying mechanisms of illness progression
— id: 139510, year: 2009, vol: 66, page: 938, stat: Journal Article,

DIFFERENTIATING VOLITION FROM HEDONIA USING A MONITARY REWARD TASK DURING FMRI
Stanford, AD; Lai, G; Luber, B; Moeller, J; Baboumian, S; Hirsch, J; Malaspina, D; Lisanby, SH
2009 MAR ;35(1-3):165-166, Schizophrenia bulletin
— id: 97767, year: 2009, vol: 35, page: 165, stat: Journal Article,

Differentiation of Reward Dependent Behavior Circuitry from Reward Anticipation with fMRI-Guided TMS
Stanford, AD; Luber, B; Lai, G; Baboumian, S; Moeller, J; Hirsch, J; Malaspina, D; Lisanby, SH
2009 APR 15 ;65(8):134S-134S, Biological psychiatry
— id: 97978, year: 2009, vol: 65, page: 134S, stat: Journal Article,

Childhood trauma and prodromal symptoms among individuals at clinical high risk for psychosis
Thompson, Judy L; Kelly, Meredith; Kimhy, David; Harkavy-Friedman, Jill M; Khan, Shamir; Messinger, Julie W; Schobel, Scott; Goetz, Ray; Malaspina, Dolores; Corcoran, Cheryl
2009 Mar;108(1-3):176-181, Schizophrenia research
INTRODUCTION: Numerous studies point to an association between childhood trauma and the later development of psychotic illness. However, little is known about the prevalence of childhood trauma and its relationship to attenuated positive and other symptoms in individuals at heightened clinical risk for psychosis. METHOD: Thirty clinical high-risk patients (83% male, 43% Caucasian, and with a mean age of 19) were ascertained from the New York metropolitan area and evaluated for prodromal and affective symptoms, and queried regarding experiences of childhood trauma and abuse. RESULTS: Ninety-seven percent endorsed at least one general trauma experience, 83% reported physical abuse, 67% emotional abuse, and 27% sexual abuse. As hypothesized, total trauma exposure was positively associated with severity of attenuated positive symptoms (in particular grandiosity), an effect primarily accounted for by ethnic minority participants, who reported greater exposure to trauma. Trauma exposure was related to affective symptoms only in the Caucasian subgroup. CONCLUSIONS: Childhood trauma was commonly self-reported, especially among clinical high-risk patients from ethnic minorities, for whom trauma was related to positive symptoms. Future areas of research include an evaluation of potential mechanisms for this relationship, including neuroendocrine and subcortical dopaminergic function
— id: 95336, year: 2009, vol: 108, page: 176, stat: Journal Article,

Emotion antecedents in schizophrenia
Tremeau, Fabien; Antonius, Daniel; Goggin, Michelle; Czobor, Pal; Butler, Pamela; Malaspina, Dolores; Gorman, Jack M
2009 Aug 30;169(1):43-50, Psychiatry research
Emotion antecedents are defined as external or internal events that cause emotions in individuals. Their study brings us insight into individuals' emotion processing. Emotion antecedents have rarely been studied in schizophrenia. Thirty individuals with schizophrenia and 30 non-patient comparison subjects, matched by gender and age, related events when they felt extremely angry, disgusted, fearful, happy, sad and surprised. Each antecedent was summarized in a written sentence and 20 judges matched the antecedent with the correct emotion. The antecedents of individuals with schizophrenia were less frequently matched with their emotion than the antecedents of non-patient comparison subjects for all emotions. Moreover, error pattern analyses revealed distinct deficits for the emotion 'fear'. In the schizophrenia group, fear antecedents were more frequently judged as non-emotional, and non-fear antecedents were more often judged as fear antecedents when compared to the control group. A deficit in fear processing correlated with the Suspiciousness item on the Brief Psychiatric Rating Scale. Our results indicate differences in emotion processing in schizophrenia. Error pattern results are consistent with impairment in the appraisal of fear. Lower accuracy rates with schizophrenia subjects' antecedents may reflect lower emotion awareness for all emotions in schizophrenia. This study furthers the understanding of deficits in basic emotion processing in schizophrenia
— id: 104100, year: 2009, vol: 169, page: 43, stat: Journal Article,

Stigma in families of individuals in early stages of psychotic illness: family stigma and early psychosis
Wong, Celine; Davidson, Larry; Anglin, Deirdre; Link, Bruce; Gerson, Ruth; Malaspina, Dolores; McGlashan, Thomas; Corcoran, Cheryl
2009 May;3(2):108-115, Early Intervention in Psychiatry
AIM: Stigma is pervasive among families of individuals with psychotic disorders and includes both general and 'associative' stigma - that is, the process by which a person is stigmatized by virtue of association with another stigmatized individual. These forms of stigma may present a barrier to help seeking. However, little is known about stigma in the early stages of evolving psychotic disorder. METHODS: Family members of 11 individuals at clinical high risk and of nine patients with recent-onset psychosis were evaluated for generalized and associative stigma using the Opinions about Mental Illness (modified) and the Family Experiences Interview Schedule. RESULTS: In this small study, the level of stigma was low, as families endorsed many supportive statements, for example, patients should be encouraged to vote, patients want to work, mental illness should be protected legally as a disability and parity should exist in insurance coverage. Families also endorsed that both talking and a belief in God and prayer can help someone get better. Only ethnic minority families of individuals with recent-onset psychosis endorsed a sense of shame and need to conceal the patient's illness. CONCLUSIONS: This preliminary study suggests that family stigma is low in the early stages of psychotic disorder, a finding that requires further investigation in a larger and more representative sample. This may be an opportune time to engage young people and families, so as to reduce duration of untreated illness. Ethnic differences in stigma, if replicated, highlight the need for cultural sensitivity in engaging individuals and their families in treatment
— id: 138413, year: 2009, vol: 3, page: 108, stat: Journal Article,

Ethnicity effects on clinical diagnoses compared to best-estimate research diagnoses in patients with psychosis: a retrospective medical chart review
Anglin, Deidre M; Malaspina, Dolores
2008 Jun;69(6):941-945, Journal of clinical psychiatry
OBJECTIVE: Ethnicity effects on diagnoses are frequently reported and have variably been attributed to diagnostic biases versus ethnic differences in environmental exposures, and other factors. METHOD: We compared best-estimate gold standard research diagnoses to clinical diagnoses (DSM-III-R and DSM-IV criteria) among 129 white, 57 African American, and 50 Hispanic patients with psychosis admitted to an inpatient research unit from 1990 to 2003. RESULTS: Clinical and research diagnoses showed greater agreement in Hispanic than in African American patients (white patients were intermediate). Diagnostic agreement for paranoid schizophrenia was likewise the best in Hispanic patients. While paranoid schizophrenia tended to be overdiagnosed in African American patients, it was underdiagnosed in white patients. Patterns of diagnostic agreement for schizoaffective disorder and 'other' diagnoses were similar among the 3 ethnic groups. CONCLUSIONS: Diagnostic unreliability may explain the excess of paranoid schizophrenia reported for African Americans. Further research is needed to elucidate the influence of ethnicity on clinical diagnosis before other theories to explain group differences can be reasonably proposed and reliably tested
— id: 80972, year: 2008, vol: 69, page: 941, stat: Journal Article,

Racial and ethnic effects on psychotic psychiatric diagnostic changes from admission to discharge: a retrospective chart review
Anglin, Deidre M; Malaspina, Dolores
2008 Mar;69(3):464-469, Journal of clinical psychiatry
OBJECTIVE: Different cultural norms for paranoia that exist among African Americans may be misconstrued and fuel the overdiagnosis of schizophrenia. The present study examined whether the frequency of psychotic psychiatric diagnoses differs by race/ethnicity, particularly with regard to paranoid schizophrenia. We examined the frequency upon admission and at discharge and further explored the pattern of diagnostic changes that occurred by racial/ethnic group. METHOD: The present study is a secondary analysis of diagnostic data obtained on inpatients admitted to a research unit from 1990 to 2003 with a typical length of stay from 3 to 6 months. Admission and discharge diagnoses were obtained from each chart on the sample of 238 patients, 55% (N = 130) of whom were white; 24% (N = 58), African American; and 21% (N = 50), Latino. Inpatients were grouped into 4 diagnostic categories: schizoaffective disorder, paranoid schizophrenia, schizophrenia-undifferentiated or -disorganized type, and other psychotic disorder. RESULTS: Upon admission, African American patients were more likely to receive a less-defined diagnosis, such as psychosis not otherwise specified, in part because they tended on average to be younger. Over the course of hospitalization, diagnoses for white patients were more likely to move toward schizoaffective at discharge (OR = 6.85, 95% CI = 1.53 to 30.66). African American patients were more likely to experience a diagnostic change to paranoid schizophrenia (OR = 4.58, 95% CI = 1.70 to 13.36). Interestingly, Latino patients were the least likely group to experience diagnostic changes during their hospitalization stay. CONCLUSIONS: The present preliminary findings reveal an interesting pattern of diagnostic changes that occurred over the course of hospitalization that should be followed up in a comprehensive study
— id: 80973, year: 2008, vol: 69, page: 464, stat: Journal Article,

Temporal association of cannabis use with symptoms in individuals at clinical high risk for psychosis
Corcoran, Cheryl M; Kimhy, David; Stanford, Arielle; Khan, Shamir; Walsh, Julie; Thompson, Judy; Schobel, Scott; Harkavy-Friedman, Jill; Goetz, Ray; Colibazzi, Tiziano; Cressman, Victoria; Malaspina, Dolores
2008 Dec;106(2-3):286-293, Schizophrenia research
BACKGROUND: Cannabis use is reported to increase the risk for psychosis, but no prospective study has longitudinally examined drug use and symptoms concurrently in clinical high risk cases. METHOD: We prospectively followed for up to 2 years 32 cases who met research criteria for prodromal psychosis to examine the relationship between substance use and clinical measures. RESULTS: Cases with a baseline history of cannabis use (41%) were older, but did not differ in clinical measures. Longitudinal assessments showed these cases had significantly more perceptual disturbances and worse functioning during epochs of increased cannabis use that were unexplained by concurrent use of other drugs or medications. CONCLUSIONS: These data demonstrate that cannabis use may be a risk factor for the exacerbation of subthreshold psychotic symptoms, specifically perceptual disturbances, in high risk cases
— id: 95338, year: 2008, vol: 106, page: 286, stat: Journal Article,

Sleep duration associated with mortality in elderly, but not middle-aged, adults in a large US sample
Gangwisch, James E; Heymsfield, Steven B; Boden-Albala, Bernadette; Buijs, Ruud M; Kreier, Felix; Opler, Mark G; Pickering, Thomas G; Rundle, Andrew G; Zammit, Gary K; Malaspina, Dolores
2008 Aug 1;31(8):1087-1096, Sleep
STUDY OBJECTIVES: To explore age differences in the relationship between sleep duration and mortality by conducting analyses stratified by age. Both short and long sleep durations have been found to be associated with mortality. Short sleep duration is associated with negative health outcomes, but there is little evidence that long sleep duration has adverse health effects. No epidemiologic studies have published multivariate analyses stratified by age, even though life expectancy is 75 years and the majority of deaths occur in the elderly. DESIGN: Multivariate longitudinal analyses of the first National Health and Nutrition Examination Survey using Cox proportional hazards models. SETTING: Probability sample (n = 9789) of the civilian noninstitutionalized population of the United States between 1982 and 1992. PARTICIPANTS: Subjects aged 32 to 86 years. MEASUREMENTS AND RESULTS: In multivariate analyses controlling for many covariates, no relationship was found in middle-aged subjects between short sleep of 5 hours or less and mortality (hazards ratio [HR] = 0.67, 95% confidence interval [CI] 0.43-1.05) or long sleep of 9 hours or more and mortality (HR = 1.04, 95% CI 0.66-1.65). A U-shaped relationship was found only in elderly subjects, with both short sleep duration (HR = 1.27, 95% CI 1.06-1.53) and long sleep duration (HR = 1.36, 95% CI 1.15-1.60) having significantly higher HRs. CONCLUSIONS: The relationship between sleep duration and mortality is largely influenced by deaths in elderly subjects and by the measurement of sleep durations closely before death. Long sleep duration is unlikely to contribute toward mortality but, rather, is a consequence of medical conditions and age-related sleep changes
— id: 80969, year: 2008, vol: 31, page: 1087, stat: Journal Article,

The Public Hospital in American Medical Education
Gourevitch, Marc N; Malaspina, Dolores; Weitzman, Michael; Goldfrank, Lewis R
2008 Sep;85(5):779-786, Journal of urban health
The importance of the public hospital system to medical education is often absent from the debate about its value. Best known as a core provider of services to the underserved, the safety net hospital system also plays a critical role in the education of future physicians. Particular strengths include its ability to imbue physicians in training with core professional values, to reveal through the enormous range of clinical experience provided many of the social forces shaping health, and to foster interest in and commitment to advancing population health. Faculty teaching in the public hospital system has unusual opportunities to reveal to learners the broader meanings of their diverse and rich experiences. Now, as an alarming array of pressures bearing down on the safety net system threaten its stability, the potential negative impact on medical education, were it to shrink or be forced to change its essential mission, must be considered. As advocates of the safety net system marshal forces to rationalize its funding and support, its tremendous contribution to the training of physicians and other health care professionals must be clearly set forth to ensure that support for the public hospital system's health is appropriately broad based
— id: 80970, year: 2008, vol: 85, page: 779, stat: Journal Article,

Twin pregnancy and the risk of schizophrenia
Kleinhaus, K; Harlap, S; Perrin, M C; Manor, O; Calderon-Margalit, R; Friedlander, Y; Malaspina, D
2008 Oct;105(1-3):197-200, Schizophrenia research
BACKGROUND: Twins are exposed to intrauterine environments that differ significantly from those of singletons. These diverse environments might alter the risk for schizophrenia in twins and make it difficult to generalize from findings in twins when studying the risk of schizophrenia in the general population. Previous studies report contradictory findings on the risk for schizophrenia in twins. METHODS: We studied the incidence of schizophrenia spectrum disorders, ascertained from Israel's National Psychiatric Registry, in a cohort of 2124 twins and 87,955 singletons. These offspring were followed from their birth in 1964-76 in the Jerusalem Perinatal study. Cox proportional hazards methods were used to compare outcomes over 28-41 years, adjusting for ages of parents. RESULTS: Twins showed a relative risk [RR] of .84 relative to singletons, with a 95% confidence interval [CI] of (.51-1.4). RRs and CIs for males and females were .68 [.34-1.4] and 1.1 [.55-2.2] respectively. Twins in male-male, female-female or opposite-sex sets showed no significant variation in RRs; furthermore, first- or second-born twins did not differ significantly from each other. Siblings of twins had the same risk of schizophrenia as siblings of singletons. CONCLUSION: Twins have the same risk for schizophrenia as the general population
— id: 93358, year: 2008, vol: 105, page: 197, stat: Journal Article,

Paternal age and twinning in the Jerusalem Perinatal Study
Kleinhaus, K; Perrin, M C; Manor, O; Friedlander, Y; Calderon-Margalit, R; Harlap, S; Malaspina, D
2008 Dec;141(2):119-122, European journal of obstetrics, gynecology & reproductive biology
OBJECTIVE: To investigate whether incidence of twin deliveries is related to father's age, independently of mother's age, and whether it differs for same-sex or opposite-sex twin sets. STUDY DESIGN: In a program of research on effects of paternal age, this study used data from a prospective cohort of 92,408 offspring born in Jerusalem from 1964 to 1976. Of the 91,253 deliveries in the Jerusalem Perinatal Study, 1115 were twin deliveries. The data were analyzed with General Estimate Equations to inform unconditional logistic regression. RESULTS: After controlling for maternal age, odds ratios (ORs) and 95% confidence intervals (95% CI) associated with father's ages 25-34 and 35+ were 1.3 (1.1, 1.7) and 1.5 (1.2, 2.1) respectively, compared with fathers <25 years old. The effect of maternal age was partly explained by paternal age. The ORs for opposite-sex twin sets and male-male twin sets increased slightly with paternal age, while the OR for same-sex and female-female twin decreased. CONCLUSION: Studies of twins are used to estimate effects of genes and environment in a variety of diseases. Our findings highlight the need to consider paternal as well as maternal age when analyzing data on twins to explore etiology of diseases
— id: 97574, year: 2008, vol: 141, page: 119, stat: Journal Article,

Acute maternal stress in pregnancy and schizophrenia in offspring: a cohort prospective study
Malaspina, D; Corcoran, C; Kleinhaus, K R; Perrin, M C; Fennig, S; Nahon, D; Friedlander, Y; Harlap, S
2008 ;8:71-71, BMC Psychiatry
Schizophrenia has been linked with intrauterine exposure to maternal stress due to bereavement, famine and major disasters. Recent evidence suggests that human vulnerability may be greatest in the first trimester of gestation and rodent experiments suggest sex specificity. We aimed to describe the consequence of an acute maternal stress, through a follow-up of offspring whose mothers were pregnant during the Arab-Israeli war of 1967. A priori, we focused on gestational month and offspring's sex. METHOD: In a pilot study linking birth records to Israel's Psychiatric Registry, we analyzed data from a cohort of 88,829 born in Jerusalem in 1964-76. Proportional hazards models were used to estimate the relative risk (RR) of schizophrenia, according to month of birth, gender and other variables, while controlling for father's age and other potential confounders. Other causes of hospitalized psychiatric morbidity (grouped together) were analyzed for comparison. RESULTS: There was a raised incidence of schizophrenia for those who were in the second month of fetal life in June 1967 (RR = 2.3, 1.1-4.7), seen more in females (4.3, 1.7-10.7) than in males (1.2, 0.4-3.8). Results were not explained by secular or seasonal variations, altered birth weight or gestational age. For other conditions, RRs were increased in offspring who had been in the third month of fetal life in June 1967 (2.5, 1.2-5.2), also seen more in females (3.6, 1.3-9.7) than males (1.8, 0.6-5.2). CONCLUSION: These findings add to a growing literature, in experimental animals and humans, attributing long term consequences for offspring of maternal gestational stress. They suggest both a sex-specificity and a relatively short gestational time-window for gestational effects on vulnerability to schizophrenia
— id: 97445, year: 2008, vol: 8, page: 71, stat: Journal Article,

Epidemiological and genetic aspects of neuropsychiatric disorders
Malaspina, Dolores; Corcoran, Cheryl; Schobel, Scott; Hamilton, Steven P
The American Psychiatric Publishing textbook of neuropsychiatry and behavioral neurosciences Arlington, VA, US: American Psychiatric Publishing, Inc., 2008,
(from the chapter) The last decade has witnessed a revolution in our understanding of the etiology of many neuropsychiatric disorders. Advances in statistical genetics, genetic epidemiology, and molecular biology have provided new insights and avenues for conducting genetic and epidemiological studies and for analyzing gene-environment interactions. The recent sequencing of the human genome now sets the stage for even greater progress in the coming years. In this chapter, we first focus on the methods of genetic epidemiology and then review some of the recent findings of these disciplines in the study of neuropsychiatric disorders
— id: 4929, year: 2008, vol: , page: 301, stat: Chapter,

Factors in the etiology of schizophrenia: Genes, parental age, and environment
Opler M.G.A.; Perrin M.C.; Kleinhaus K.; Malaspina D.
2008 ;15(6):37-45, Primary Psychiatry
Schizophrenia is a brain disorder with a complex etiology believed to have both genetic and environmental risk factors. Although the precise pathology of the disease and the mechanisms that cause the emergence of symptoms remain elusive, understanding the causes of schizophrenia and its risk factors have evolved considerably over the past decade. The discussion has shifted from the reductionist 'genes versus environment' debate to a more integrative approach, ie, the functions of susceptibility genes, epigenetics and paternal age, and toxic exposures throughout early development. This article discusses evidence for three major categories of risk factors, including genetic contributions, the role of paternal age and potential mechanisms by which it exerts its influence on risk, and new findings on the role of environmental exposures
— id: 80326, year: 2008, vol: 15, page: 37, stat: Journal Article,

Family history and paternal age-related gender effects on schizophrenia reoccurrence in the jerusalem cohort
Perrin, MC; Harlap, S; Kleinhaus, K; Opler, M; Lichtenberg, R; Draiman, BG; Manor, O; Malaspina, D
2008 APR 1 ;63(7):271S-271S, Biological psychiatry
— id: 78671, year: 2008, vol: 63, page: 271S, stat: Journal Article,

Hypermetabolism in the CA1 subfield of the hippocampal formation is a primary defect underlying psychotic features of schizophrenia
Schobel, S; Lewandowski, N; Corcoran, C; Muhammad, A; Moore, H; Brown, T; Malaspina, D; Small, S
2008 OCT ;2(1):A35-A35, Early Intervention in Psychiatry
— id: 100042, year: 2008, vol: 2, page: A35, stat: Journal Article,

rTMS strategies for the study and treatment of schizophrenia: a review
Stanford, Arielle D; Sharif, Zafar; Corcoran, Cheryl; Urban, Nina; Malaspina, Dolores; Lisanby, Sarah H
2008 Jun;11(4):563-576, International journal of neuropsychopharmacology
Transcranial magnetic stimulation (TMS) and repetitive TMS (rTMS) have been used increasingly over the past few years to study both the pathophysiology of schizophrenia as well as the utility of focal neuromodulation as a novel treatment for schizophrenia. rTMS treatment studies to date have explored its effect on both positive and negative symptoms by targeting cortical regions thought to underlie these symptom clusters. Studies on auditory hallucinations have been largely positive, while efficacy for negative symptoms is equivocal. A better understanding of the functional abnormalities that accompany symptoms may facilitate the development of rTMS as a treatment modality. Furthermore, schizophrenia patients appear to have abnormal cortical inhibition, consistent with GABA and dopamine abnormalities in schizophrenia. The effect of TMS on GABA and dopamine neurotransmission has not been clearly delineated. Given the variability in cortical response to rTMS in schizophrenia, methods to optimize dosage are essential. Consideration of these factors among others may broaden the scope of utility of TMS for schizophrenia as well as enhance its efficacy
— id: 80975, year: 2008, vol: 11, page: 563, stat: Journal Article,

Loss aversion in schizophrenia
Tremeau, Fabien; Brady, Melissa; Saccente, Erica; Moreno, Alexis; Epstein, Henry; Citrome, Leslie; Malaspina, Dolores; Javitt, Daniel
2008 Aug;103(1-3):121-128, Schizophrenia research
BACKGROUND: Loss aversion in decision-making refers to a higher sensitivity to losses than to gains. Loss aversion is conceived as an affective interference in cognitive processes such as judgment and decision-making. Loss aversion in non-risky choices has not been studied in schizophrenia. METHOD: Forty-two individuals with schizophrenia and 42 non-patient control subjects, matched by gender and age, were randomized to two different scenarios (a buying scenario and a selling scenario). Subjects were asked to evaluate the price of a decorated mug. Schizophrenia subjects were re-tested four weeks later with the other scenario. RESULTS: Contrary to non-patient controls, schizophrenia subjects did not show loss aversion. In the schizophrenia group, absence of loss aversion was correlated with age, duration of illness, number of months in State hospitals, and poorer performance in the Wisconsin Card Sorting Test, but not with current psychopathology and two domains of emotional experience. CONCLUSIONS: Absence of loss aversion in schizophrenia represents a deficit in the processing of emotional information during decision-making. It can be interpreted as a lack of integration between the emotional and the cognitive systems, or to a more diffuse and de-differentiated impact of emotional information on decision-making. Future studies should bring more clarity to this question
— id: 80971, year: 2008, vol: 103, page: 121, stat: Journal Article,

Advanced parental age at birth is associated with poorer social functioning in adolescent males: shedding light on a core symptom of schizophrenia and autism
Weiser, Mark; Reichenberg, Abraham; Werbeloff, Nomi; Kleinhaus, Karine; Lubin, Gad; Shmushkevitch, Moti; Caspi, Asaf; Malaspina, Dolores; Davidson, Michael
2008 Nov;34(6):1042-1046, Schizophrenia bulletin
BACKGROUND: Evidence indicates an association between older parents at birth and increased risk for schizophrenia and autism. Patients with schizophrenia and autism and their first-degree relatives have impaired social functioning; hence, impaired social functioning is probably an intermediate phenotype of the illness. This study tested the hypothesis that advanced father's age at birth would be associated with poorer social functioning in the general population. To test this hypothesis, we examined the association between parental age at birth and the social functioning of their adolescent male offspring in a population-based study. METHODS: Subjects were 403486, 16- to 17-year-old Israeli-born male adolescents assessed by the Israeli Draft Board. The effect of parental age on social functioning was assessed in analyses controlling for cognitive functioning, the other parent's age, parental socioeconomic status, birth order, and year of draft board assessment. RESULTS: Compared with offspring of parents aged 25-29 years, the prevalence of poor social functioning was increased both in offspring of fathers younger than 20 years (odds ratio [OR] = 1.27, 95% confidence interval [CI] = 1.08-1.49) and in offspring of fathers 45 years old (OR = 1.52, 95% CI = 1.43-1.61). Male adolescent children of mothers aged 40 years and above were 1.15 (95% CI = 1.07-1.24) times more likely to have poor social functioning. CONCLUSIONS: These modest associations between parental age and poor social functioning in the general population parallel the associations between parental age and risk for schizophrenia and autism and suggest that the risk pathways between advanced parental age and schizophrenia and autism might, at least partially, include mildly deleterious effects on social functioning
— id: 95339, year: 2008, vol: 34, page: 1042, stat: Journal Article,

Comparable family burden in families of clinical high-risk and recent-onset psychosis patients
Wong C; Davidson L; McGlashan T; Gerson R; Malaspina D; Corcoran C
2008 Nov 1;2(4):256-261, Early Intervention in Psychiatry
AIM: Family burden is prevalent in psychotic disorders, but little is known about burden experienced by families of patients in early illness. In this exploratory study, we examined the extent of burden reported by families of patients during a putative prodromal period and in the after-math of psychosis onset. METHODS: Family burden was assessed in 23 family members of patients with emerging or early psychosis. The Family Experiences Interview Schedule was used to assess both objective and subjective burden. Objective burden is comprised of increased resource demands and disruption of routine. Subjective burden includes worry, anger/displeasure and resentment at objective burden. RESULTS: Family burden was comparable for the clinical high-risk and recent-onset psychosis patients. Worry was as high as previously reported for more chronic patients. By contrast, there was a relative absence of displeasure/anger. Family members endorsed assisting patients in activities of daily living, although not 'minding' doing so, and reported little need to supervise or control patients' behaviour. CONCLUSIONS: Early in emerging psychotic illness, families report helping patients and worrying about them, but their lives are not yet disrupted and they do not have much anger or resentment. This may be an ideal time then for intervention with families, as worry may motivate help-seeking by families
— id: 129210, year: 2008, vol: 2, page: 256, stat: Journal Article,

Insight into illness and adherence to psychotropic medications are separately associated with violence severity in a forensic sample
Alia-Klein, Nelly; O'Rourke, Thomas M; Goldstein, Rita Z; Malaspina, Dolores
2007 Jan-Feb;33(1):86-96, Aggressive Behavior
Violence towards others by a minority of psychotic individuals is a significant public health concern. The severity of this other-directed violence (ODV) in the community may be influenced by insight into illness and adherence to psychotropic medications; however, few studies have tested these associations. Sixty male psychotic inpatients, legally detained at a forensic unit in New York City, were assessed with semi-structured interviews, supplemented with information from hospital and official records, family members and the treating clinician. Results indicated that in this unique sample of detained persons with psychotic disorders; (1) increase in the severity of community violence is associated with medication non-adherence, all dimensions of poor insight into illness, and several previously reported covariates such as substance use comorbidity; (2) no relationship was found between insight and adherence in this particular sample; (3) multivariate analyses showed that select covariates, along with medication adherence, and select insight domains predicted a total of 73% of the magnitude of ODV behavior in this sample. Overall, medication non-adherence explained a large amount of how violently participants behaved toward others. Since non-adherence was independent of poor insight, it may be more worthwhile for clinicians to develop treatment strategies to target medication adherence without directly addressing an elusive target such as insight into illness. Treatment addressing medication adherence needs to concomitantly target substance use behaviors since the latter was responsible for a substantial increase in ODV
— id: 80981, year: 2007, vol: 33, page: 86, stat: Journal Article,

Trajectory to a first episode of psychosis: a qualitative research study with families
Corcoran C; Gerson R; Sills-Shahar R; Nickou C; McGlashan T; Malaspina D; Davidson L
2007 Nov;1(4):308-315, Early Intervention in Psychiatry
AIM: The trajectory in psychotic disorders which leads from a relatively normal premorbid state in young people to a first episode of psychosis is only partly understood. Qualitative research methods can be used to begin to elucidate the temporal unfolding of symptoms leading to a first episode of psychosis, and its impact on families. METHODS: We conducted open-ended interviews with family members of 13 patients with recent onset non-affective psychotic disorders, which focused on changes observed, effects on the family, explanatory models, help-seeking patterns and future expectations. Standard data analytic methods employed for qualitative research were used. RESULTS: Narratives by family members were remarkably similar. First, social withdrawal and mood symptoms developed in previously normal children; these changes were typically ascribed to drugs or stress, or to the 'storminess' of adolescence. Coping strategies by family members included prayer and reasoning/persuasion with the young person, and family initially sought help from friends and religious leaders. Entry into the mental health system was then catalysed by the emergence of overt symptoms, such as 'hearing voices', or violent or bizarre behaviour. Family members perceived inpatient hospitalization as traumatic or difficult, and had diminished expectations for the future. CONCLUSIONS: Understanding families' explanatory models for symptoms and behavioural changes, and their related patterns of help-seeking, may be useful for understanding evolution of psychosis and for the design of early intervention programmes. Dissatisfaction with hospitalization supports the mandate to improve systems of care for recent-onset psychosis patients, including destigmatization and a focus on recovery
— id: 95340, year: 2007, vol: 1, page: 308, stat: Journal Article,

Orbitofrontal dysfunction in a monozygotic twin discordant for postpartum affective psychosis: a functional magnetic resonance imaging study
Fahim, Cherine; Stip, Emmanuel; Mancini-Marie, Adham; Potvin, Stephane; Malaspina, Dolores
2007 Aug;9(5):541-545, Bipolar disorders
BACKGROUND: Incomplete concordance for psychosis in monozygotic (MZ) twins has been interpreted as indicative of non-genetic cofactors in transmission of the illness. In this case study, we consider childbirth a landmark in the onset of psychotic symptoms, leading to the diagnosis of puerperal psychosis and then to bipolar/schizoaffective disorder. At the end of the third trimester, there is a sudden drop in estrogen, which exerts prominent effects on the serotonergic system in the orbitofrontal cortex (OFC). OBJECTIVES: The purpose of the present study was to investigate OFC activation during emotional processing in MZ twins discordant for affective psychosis. METHODS: Blood-oxygen-level-dependent activation using functional magnetic resonance imaging was measured during the passive viewing of emotional film excerpts. RESULTS: Consistent with our hypothesis, a significant locus of activation was found in the left OFC in the normal MZ twin, but not in the psychosis MZ twin. CONCLUSIONS: The personality changes noted in the psychosis MZ twin (postpartum psychosis) may be related to dysfunctional OFC. Ms J's childbirth may have triggered the onset of psychotic symptoms, leading to the diagnosis of bipolar or schizoaffective disorder
— id: 80979, year: 2007, vol: 9, page: 541, stat: Journal Article,

Sleep duration as a risk factor for diabetes incidence in a large U.S. sample
Gangwisch, James E; Heymsfield, Steven B; Boden-Albala, Bernadette; Buijs, Ruud M; Kreier, Felix; Pickering, Thomas G; Rundle, Andrew G; Zammit, Gary K; Malaspina, Dolores
2007 Dec 1;30(12):1667-1673, Sleep
STUDY OBJECTIVES: To explore the relationship between sleep duration and diabetes incidence over an 8- to 10-year follow-up period in data from the First National Health and Nutrition Examination Survey (NHANES I). We hypothesized that prolonged short sleep duration is associated with diabetes and that obesity and hypertension act as partial mediators of this relationship. The increased load on the pancreas from insulin resistance induced by chronically short sleep durations can, over time, compromise beta-cell function and lead to type 2 diabetes. No plausible mechanism has been identified by which long sleep duration could lead to diabetes. DESIGN: Multivariate longitudinal analyses of the NHANES I using logistic regression models. SETTING: Probability sample (n=8992) of the noninstitutionalized population of the United States between 1982 and 1992. PARTICIPANTS: Subjects between the ages of 32 and 86 years. MEASUREMENTS AND RESULTS: Between 1982 and 1992, 4.8% of the sample (n=430) were determined by physician diagnosis, hospital record, or cause of death to be incident cases of diabetes. Subjects with sleep durations of 5 or fewer hours (odds ratio = 1.47, 95% confidence interval 1.03-2.09) and subjects with sleep durations of 9 or more hours (odds ratio = 1.52, 95% confidence interval 1.06-2.18) were significantly more likely to have incident diabetes over the follow-up period after controlling for covariates. CONCLUSIONS: Short sleep duration could be a significant risk factor for diabetes. The association between long sleep duration and diabetes incidence is more likely to be due to some unmeasured confounder such as poor sleep quality
— id: 80974, year: 2007, vol: 30, page: 1667, stat: Journal Article,

Validity of a 'proxy' for the deficit syndrome derived from the Positive And Negative Syndrome Scale (PANSS)
Goetz, Raymond R; Corcoran, Cheryl; Yale, Scott; Stanford, Arielle D; Kimhy, David; Amador, Xavier; Malaspina, Dolores
2007 Jul;93(1-3):169-177, Schizophrenia research
Schizophrenia patients with the deficit syndrome (DS) may represent a homogeneous subgroup. To increase the practicability of diagnosing the DS, Kirkpatrick et al. [Kirkpatrick, B., Buchanan, RW., Breier, A. Carpenter, WT., 1993. Case identification and stability of the deficit syndrome of schizophrenia. Psychiatry Res. 47, 47-56.] proposed the use of a 'proxy' case identification tool using standardized symptom ratings instead of the Schedule for the Deficit Syndrome (SDS) which requires an independent clinical assessment. The Proxy for the Deficit Syndrome (PDS) is based on the extraction of symptoms that are essentially equivalent or overlap substantially with the restricted affect and diminished emotional range on the SDS. Kirkpatrick et al. [Kirkpatrick, B., Buchanan, RW., Breier, A. Carpenter, WT., 1993. Case identification and stability of the deficit syndrome of schizophrenia. Psychiatry Res. 47, 47-56.] reported good sensitivity and specificity in a comparison of SDS and PDS assessments among 100 chronic schizophrenia outpatients. The present investigation involves the comparison of the deficit syndrome as assessed by the 'gold standard' Schedule for the Deficit Syndrome with the ratings of the same symptoms embodied in the 'proxy instrument' the PANSS, within the same group of 156 inpatients. Forty-four patients were assessed by the SDS to have the deficit syndrome. Patients with and without the DS, as defined by the SDS, did not differ for age, education, age at illness onset and duration of illness. The two main 'proxy' measures PDS1 and PDS2 discriminated across the SDS groups. The direct dichotomous comparison of the actual SDS and the 'proxy' derived PDS groups demonstrated good specificity (78.6% and 79.5%) and moderate to very good sensitivity (61.4% and 86.4%) and there was a moderately low rate of false positive cases (21.4% and 20.5%). For the two main 'proxy' measures (PDS1 and PDS2) kappas were .38 and .59, representing poor to good agreement. In our sample of rigorously diagnosed schizophrenia inpatients, the use of a 'proxy' case identification tool for the deficit syndrome would appear to be a viable alternative in identifying a subgroup of schizophrenia patients with the deficit syndrome when the use of the actual SDS is not feasible. Further study is indicated before the PDS as extracted from the PANSS can be used in lieu of the SDS for identifying patients with this syndrome
— id: 80982, year: 2007, vol: 93, page: 169, stat: Journal Article,

The Jerusalem Perinatal Study cohort, 1964-2005: methods and a review of the main results
Harlap, Susan; Davies, A Michael; Deutsch, Lisa; Calderon-Margalit, Ronit; Manor, Orly; Paltiel, Ora; Tiram, Efrat; Yanetz, Rivka; Perrin, Mary C; Terry, Mary B; Malaspina, Dolores; Friedlander, Yechiel
2007 May;21(3):256-273, Paediatric & perinatal epidemiology
The Jerusalem Perinatal Study recorded information on population-based cohorts of 92 408 live- and stillbirths in 1964-76, and their parents, with active surveillance of infant deaths and birth defects. Data on maternal conditions, obstetric complications and interventions during labour and delivery were recorded for 92% of the births. Subsets were surveyed with antenatal interviews in 1965-68 (n = 11 467), paediatric admissions to hospital (n = 17 782) and postpartum interviews in 1975-76 (n = 16 912). Data from some offspring were linked to records of a health examination at age 17. The offspring, mothers and fathers have been traced recently, their vital status assessed, and the data linked to Israel's Cancer Registry and Psychiatric Registry. This paper describes the different types of data available, their sources, and some potential biases. Characteristics of this unique population are shown. Findings from the study are reviewed and a list of references is provided. The cohorts provide a unique source of data for a wide variety of studies
— id: 76378, year: 2007, vol: 21, page: 256, stat: Journal Article,

Visual form perception: a comparison of individuals at high risk for psychosis, recent onset schizophrenia and chronic schizophrenia
Kimhy, D; Corcoran, C; Harkavy-Friedman, J M; Ritzler, B; Javitt, D C; Malaspina, D
2007 Dec;97(1-3):25-34, Schizophrenia research
Schizophrenia has been associated with deficits in visual perception and processing, but there is little information about their temporal development and stability. We assessed visual form perception using the Rorschach Comprehensive System (RCS) in 23 individuals at clinical high risk for psychosis, 15 individuals with recent onset schizophrenia (< or =2 years since onset), and 34 with chronic schizophrenia (> or =3 years since onset). All three groups demonstrated reduced conventional form perception (X+%), as compared with published norms, but did not differ significantly from one another. In contrast, the high-risk group had significantly better performance on an index of clarity of conceptual thinking (WSUM6) compared to the chronic schizophrenia patients, with the recent onset group scoring intermediate to the high-risk and chronic schizophrenia groups. The results suggest that individuals at clinical high risk for psychosis display substantial deficits in visual form perception prior to the onset of psychosis and that these deficits are comparable in severity to those observed in individuals with schizophrenia. Therefore, visual form perception deficits may constitute a trait-like risk factor for psychosis in high-risk individuals and may potentially serve as an endophenotype of risk for development of psychosis. Clarity of conceptual thinking was relatively preserved among high-risk patients, consistent with a relationship to disease expression, not risk. These deficits are discussed in the context of the putative neurobiological underpinnings of visual deficits and the developmental pathophysiology of psychosis in schizophrenia
— id: 150709, year: 2007, vol: 97, page: 25, stat: Journal Article,

Revisiting the backward masking deficit in schizophrenia: individual differences in performance and modeling with transcranial magnetic stimulation
Luber, Bruce; Stanford, Arielle D; Malaspina, Dolores; Lisanby, Sarah H
2007 Oct 1;62(7):793-799, Biological psychiatry
BACKGROUND: Deficits in backward masking have been variably reported in schizophrenia patients, but individual differences in the expression of these deficits have not been explicitly investigated. In addition, increased knowledge of the visual system has opened the door for new techniques such as transcranial magnetic stimulation (TMS) to explore these deficits physiologically. METHODS: Patients with schizophrenia and healthy controls were tested using a backward masking paradigm. In order to examine the functionality of visual pathways involved in backward masking, subjects were retested on a backward masking paradigm using single pulse TMS applied to occipital cortex in lieu of the masking stimuli. RESULTS: Compared with controls, patients had significantly delayed recovery from visual backward masking. However, 23.5% of patients (compared to 5% of controls) never recovered to levels approaching unmasked performance. When these subjects were segregated from the analysis, group differences vanished. In addition, stimulus masking with occipital TMS followed the same pattern in both patients and controls. CONCLUSIONS: Observations of individual differences in visual masking performance may identify a subgroup of schizophrenia patients. The TMS data suggest that this deficit may not localize to the occipital cortex. However, TMS can be a useful tool for localizing processing deficits in schizophrenia
— id: 80984, year: 2007, vol: 62, page: 793, stat: Journal Article,

Accumulating evidence for epigenetic effects in schizophrenia
Malaspina, Dolores
2007 ;:7-7 #P7, WCBG ... Abstract Book (World Congress on Psychiatric Genetics)
— id: 76059, year: 2007, vol: , page: 7, stat: Journal Article,

Estrogen, estrogen treatment and the post-reproductive woman's brain
Naftolin, Frederick; Malaspina, Dolores
2007 May 20;57(1):23-26, Maturitas
From early embryonic life to death, estrogen is a primary regulator of brain neurogenesis and cell number, synaptogenesis and synaptolysis, multiple cognitive and autonomic functions, vascular function, immune responses and defense measures against brain lesions and dystrophy. Although recent attention has focused on the roles of estrogen during the climacteric, knowing estrogen's role in brain development and reproductive function is necessary to understand what happens when this powerful influence is removed during the climacteric. This review will therefore address the full picture, with stress on the later-life role of estrogen in the brain
— id: 80983, year: 2007, vol: 57, page: 23, stat: Journal Article,

Aberrant epigenetic regulation could explain the relationship of paternal age to schizophrenia
Perrin, Mary C; Brown, Alan S; Malaspina, Dolores
2007 Nov;33(6):1270-1273, Schizophrenia bulletin
The causal mechanism underlying the well-established relation between advancing paternal age and schizophrenia is hypothesized to involve mutational errors during spermatogenesis that occur with increasing frequency as males age. Point mutations are well known to increase with advancing paternal age while other errors such as altered copy number in repeat DNA and chromosome breakage have in some cases also been associated with advancing paternal age. Dysregulation of epigenetic processes may also be an important mechanism underlying the association between paternal age and schizophrenia. Evidence suggests that advancing age as well as environmental exposures alter epigenetic regulation. Errors in epigenetic processes, such as parental imprinting can have serious effects on the offspring both pre- and postnatally and into adulthood. This article will discuss parental imprinting on the autosomal and X chromosomes and the alterations in epigenetic regulation that may lead to such errors
— id: 80978, year: 2007, vol: 33, page: 1270, stat: Journal Article,

Tetrachloroethylene exposure and risk of schizophrenia: offspring of dry cleaners in a population birth cohort, preliminary findings
Perrin, Mary C; Opler, Mark G; Harlap, Susan; Harkavy-Friedman, Jill; Kleinhaus, Karine; Nahon, Daniella; Fennig, Shmuel; Susser, Ezra S; Malaspina, Dolores
2007 Feb;90(1-3):251-254, Schizophrenia research
Tetrachloroethylene is a solvent used in dry cleaning with reported neurotoxic effects. Using proportional hazard methods, we examined the relationship between parental occupation as a dry cleaner and risk for schizophrenia in a prospective population-based cohort of 88,829 offspring born in Jerusalem from 1964 through 1976, followed from birth to age 21-33 years. Of 144 offspring whose parents were dry cleaners, 4 developed schizophrenia. We observed an increased incidence of schizophrenia in offspring of parents who were dry cleaners (RR=3.4, 95% CI, 1.3-9.2, p=0.01). Tetrachloroethylene exposure warrants further investigation as a risk factor for schizophrenia
— id: 76381, year: 2007, vol: 90, page: 251, stat: Journal Article,

Growth trajectory during early life and risk of adult schizophrenia
Perrin, Megan A; Chen, Henian; Sandberg, David E; Malaspina, Dolores; Brown, Alan S
2007 Dec;191:512-520, British journal of psychiatry
BACKGROUND: Growth abnormalities have been suggested as a precursor to schizophrenia, but previous studies have not assessed growth patterns using repeated measures. AIMS: To assess the association between early life/later childhood growth patterns and risk of schizophrenia. METHODS: Using prospectively collected data from a birth cohort (born 1959-1967), measurements of height, weight and body mass index (BMI) were analysed to compare growth patterns during early life and later childhood between 70 individuals with schizophrenia-spectrum disorder (SSD) and 7710 without. RESULTS: For women, growth in the SSD group was approximately 1 cm/year slower during early life (P < 0.01); no association was observed for men. Later childhood growth was not associated with SSD. Weight patterns were not associated with SSD, whereas slower change in BMI was observed among the SSD group during later childhood. CONCLUSIONS: The association between slower growth in early life and schizophrenia in women suggests that factors responsible for regulating growth might be important in the pathogenesis of the disorder
— id: 80976, year: 2007, vol: 191, page: 512, stat: Journal Article,

Socioeconomic status at birth is associated with risk of schizophrenia: population-based multilevel study
Werner, Shirli; Malaspina, Dolores; Rabinowitz, Jonathan
2007 Nov;33(6):1373-1378, Schizophrenia bulletin
BACKGROUND: Inconsistent findings obscure understanding the relationship between socioeconomic status (SES) and schizophrenia. The aim of the current study was to test the association between individual and community SES at birth and risk of schizophrenia. METHOD: Population-based longitudinal follow forward study of a 13-year birth cohort (n = 71 165). Effects of individual and community socioeconomic variables were examined using multilevel regression in MLwiN. RESULTS: Years of education of fathers and mothers, respectively, (0-8 vs 13+ odds ratio [OR] = 1.17, P < .0001; OR = 1.14, P < .001) lower occupational status of fathers (OR = 1.29, P = .036), and poorer residential area SES (OR = 1.26, P = .012) were risk factors for schizophrenia. CONCLUSIONS: Individual- and community-level SES at the time of birth are associated with an increased risk of schizophrenia
— id: 80980, year: 2007, vol: 33, page: 1373, stat: Journal Article,

Short sleep duration as a risk factor for hypertension: analyses of the first National Health and Nutrition Examination Survey
Gangwisch, James E; Heymsfield, Steven B; Boden-Albala, Bernadette; Buijs, Ruud M; Kreier, Felix; Pickering, Thomas G; Rundle, Andrew G; Zammit, Gary K; Malaspina, Dolores
2006 May;47(5):833-839, Hypertension
Depriving healthy subjects of sleep has been shown to acutely increase blood pressure and sympathetic nervous system activity. Prolonged short sleep durations could lead to hypertension through extended exposure to raised 24-hour blood pressure and heart rate, elevated sympathetic nervous system activity, and increased salt retention. Such forces could lead to structural adaptations and the entrainment of the cardiovascular system to operate at an elevated pressure equilibrium. Sleep disorders are associated with cardiovascular disease, but we are not aware of any published prospective population studies that have shown a link between short sleep duration and the incidence of hypertension in subjects without apparent sleep disorders. We assessed whether short sleep duration would increase the risk for hypertension incidence by conducting longitudinal analyses of the first National Health and Nutrition Examination Survey (n=4810) using Cox proportional hazards models and controlling for covariates. Hypertension incidence (n=647) was determined by physician diagnosis, hospital record, or cause of death over the 8- to 10-year follow-up period between 1982 and 1992. Sleep durations of < or =5 hours per night were associated with a significantly increased risk of hypertension (hazard ratio, 2.10; 95% CI, 1.58 to 2.79) in subjects between the ages of 32 and 59 years, and controlling for the potential confounding variables only partially attenuated this relationship. The increased risk continued to be significant after controlling for obesity and diabetes, which was consistent with the hypothesis that these variables would act as partial mediators. Short sleep duration could, therefore, be a significant risk factor for hypertension
— id: 69092, year: 2006, vol: 47, page: 833, stat: Journal Article,

Does unwantedness of pregnancy predict schizophrenia in the offspring? : Findings from a prospective birth cohort study
Herman, Daniel B; Brown, Alan S; Opler, Mark G; Desai, Manisha; Malaspina, Dolores; Bresnahan, Michaeline; Schaefer, Catherine A; Susser, Ezra S
2006 Aug;41(8):605-610, Social psychiatry & psychiatric epidemiology
BACKGROUND: We sought to replicate (or refute) a previous report of an association between unwantedness of a pregnancy and the risk of schizophrenia in the offspring. METHOD: The study was conducted using a large, prospectively collected birth cohort as part of the Prenatal Determinants of Schizophrenia study (PDS). Attitude toward the pregnancy was assessed at the time of the mother's first visit to the prenatal clinic. Cases of schizophrenia and other schizophrenia spectrum disorders in the offspring of these mothers were subsequently ascertained and diagnosed. In univariate and multivariate analyses, we examined the relationship between attitude toward the pregnancy and risk of adult schizophrenia and other schizophrenia spectrum disorders. RESULTS: The unadjusted hazard ratio for the association between ambivalent or negative maternal attitude toward the pregnancy and the risk of schizophrenia spectrum disorders was 1.75, (95% CI = 0.97, 3.17, P = 0.06). This result was unchanged after adjustment for social class, paternal age, race/ethnicity and other potential confounders. Similar results were observed when only cases with schizophrenia were included in the analysis. CONCLUSIONS: We did not find a statistically significant association in favor of the hypothesis that unwantedness of pregnancy is a risk factor for adult schizophrenia. On the other hand, the magnitude of the observed association was similar to the findings of the only previous study of this question and the confidence limits overlap those findings. Whether unwantedness of pregnancy is a risk factor for adult schizophrenia remains an open question that may be resolved by future research
— id: 69090, year: 2006, vol: 41, page: 605, stat: Journal Article,

Computerized experience sampling method (ESMc): assessing feasibility and validity among individuals with schizophrenia
Kimhy, David; Delespaul, Philippe; Corcoran, Cheryl; Ahn, Hongshik; Yale, Scott; Malaspina, Dolores
2006 Apr;40(3):221-230, Journal of psychiatric research
The Experience Sampling Method (ESM) is an ecologically valid, time-sampling of self-reports developed to study the dynamic process of person-environment interactions. ESM with digital wristwatch and booklets (paper-based ESM; ESMp) has been used extensively to study schizophrenia. The present study is designed to test the feasibility and validity of using Computerized ESM (ESMc) among individuals with schizophrenia. ESMc is advantageous in allowing for recording of precise time-stamps of responses. We used PDAs ('Personal Digital Assistant'; Palm handheld computers) to collect data on momentary psychotic symptoms, mood, and thoughts over a one day period among 10 hospitalized schizophrenia patients and 10 healthy controls. ESMc was equally acceptable to both groups, with similar ratings of comfort carrying the PDAs and operating them, interference with daily activities, as well as response rates. The schizophrenia patients reported significantly higher ratings of auditory and visual hallucinations, suspiciousness, sense of unreality, lack of thought control, fear of losing control, difficulty expressing thoughts, as well as depression/sadness, loneliness and less cheerfulness. Significant inverse relationships were found among both groups between ratings of feeling cheerful and being stressed, irritated, and sad/depressed. Among the schizophrenia subjects, the correlation between ratings of suspiciousness on ESMc and Scale for Assessment of Positive Symptoms (SAPS) approached significance, as well as the link between suspiciousness and stress. Our results support the feasibility and validity of using ESMc for assessment of momentary psychotic symptoms, mood, and experiences among individuals with schizophrenia. The authors discuss the potential applications of combining ESMc with ambulatory physiological measures
— id: 69094, year: 2006, vol: 40, page: 221, stat: Journal Article,

Maternal household crowding during pregnancy and the offspring's risk of schizophrenia
Kimhy, David; Harlap, Susan; Fennig, Shmuel; Deutsch, Lisa; Draiman, Benjamin G; Corcoran, Cheryl; Goetz, Deborah; Nahon, Daniella; Malaspina, Dolores
2006 Sep;86(1-3):23-29, Schizophrenia research
BACKGROUND: Animal models of schizophrenia suggest a link between maternal crowding during pregnancy and increased risk of the offspring to develop physiological, developmental, and behavioral abnormalities that are comparable to those observed in schizophrenia. We tested the hypothesis that a similar link is present in humans. METHOD: We investigated whether prenatal exposure to household crowding was associated with the risk of schizophrenia in a sub-cohort of the Jerusalem Perinatal Study (JPS) consisting 11,015 individuals born between 1964 and 1976. During these years mothers participated in face to face interviews in early pregnancy. The prenatal and birth data, including the number of rooms and individuals living in the mothers' household, was cross-linked with the Israel Psychiatric Registry by ministry personnel. RESULTS: 104 schizophrenia cases were identified in the cohort. Offspring who, while in utero, their mother resided in a household with five or more individuals had RR of 1.47 (95% CI: 0.99-2.16, p=0.05) to develop schizophrenia, compared to those whose mother resided with four or fewer individuals. However, when adjusted for paternal age, the RR was reduced to 1.18 (95% CI: 0.76-1.84, p=0.46). The number of rooms in the household and the household crowding during pregnancy did not significantly impact the offspring's risk to develop schizophrenia. CONCLUSION: The link between maternal household crowding during pregnancy and the offspring's risk of schizophrenia was explained primarily by the impact of paternal age. The authors discuss the results in view of findings from animal and human studies
— id: 69089, year: 2006, vol: 86, page: 23, stat: Journal Article,

The factorial structure of the schedule for the deficit syndrome in schizophrenia
Kimhy, David; Yale, Scott; Goetz, Raymond R; McFarr, Lynn Marcinko; Malaspina, Dolores
2006 Apr;32(2):274-278, Schizophrenia bulletin
Deficit schizophrenia (DS) is considered a distinct subtype within the diagnosis of schizophrenia. While the common assumption is that DS represents a single, cohesive domain of psychopathology, the factorial structure of DS has not been investigated. We assessed 52 individuals with DSM-IV diagnoses of schizophrenia with DS. A principal component analysis (PCA) was conducted on the symptoms of the Schedule for the Deficit Syndrome. The PCA resulted in 2 distinct factors explaining 73.8% of the variance. Factor 1 (avolition) is made up of symptoms of curbing of interests, diminished sense of purpose, and diminished social drive. Factor 2 (emotional expression) is made up of symptoms of restricted affect, diminished emotional range, and poverty of speech. The results indicate that DS is best characterized by these 2 factors. The great majority of participants (86%) displayed DS symptoms from both factors. On average, participants had 4.19 (S.D. = 1.39) symptoms that were primary, enduring, and at least moderate in severity. The mean severity of symptoms was 2.25 (S.D. = 1.06). We discuss possible links between the obtained factors and putative neurobiological mechanisms, as well as directions for future research
— id: 69097, year: 2006, vol: 32, page: 274, stat: Journal Article,

Preventing clinical deterioration in the course of schizophrenia: the potential for neuroprotection
Lieberman, Jeffrey A; Jarskog, L Fredrik; Malaspina, Dolores
2006 Jun;67(6):983-990, Journal of clinical psychiatry
— id: 80986, year: 2006, vol: 67, page: 983, stat: Journal Article,

Preventing clinical deterioration in the course of schizophrenia: the potential for neuroprotection
Lieberman, Jeffrey A; Malaspina, Dolores; Jarskog, L Fredrik
2006 ;11(4 Suppl 1):1-15 Apr, CNS spectrums
Schizophrenia, which has both genetic and environmental causes, is associated with persistent symptoms and severe functional disability. The illness lies dormant during the premorbid phase and begins to express itself during adolescence or early adulthood. Clinical progression and deterioration reaches a plateau in which the patient is said to be in the chronic phase of illness and at which point restoration of prior functioning is unlikely. The severe deficits associated with schizophrenia are often the result of progression of illness due to lack of appropriate treatment. However, recent advances in neuropsychiatry have led to very early identification of individuals at risk for psychosis, even during the prodromal stage when psychosis has not yet manifested clinically. While research has demonstrated that the efficacy of antipsychotics is limited when used during the chronic phase of illness, these medications can effectively control symptoms and prevent progression of illness when used during the early stages of illness. The evidence of neural degeneration in the pathophysiology of schizophrenic illness suggests that there may be treatment opportunities through neural protection. Neuroprotection, which refers to treatment that helps maintain central nervous system functionality in response to neurobiologic stress, may be responsible for prevention of disease progression and deterioration. In this monograph, Jeffrey L. Lieberman, MD, introduces the phases of schizophrenic illness in relation to the concepts of progression and deterioration. Next, Dolores Malaspina, MD, reviews the neurodevelopmental and neurodegenerative components of schizophrenia. Finally, L. Fredrik Jarskog, MD, focuses on the neuroprotective aspects of therapeutic interventions in schizophrenia
— id: 69091, year: 2006, vol: 11, page: 1, stat: Journal Article,

Preventing clinical deterioration in the course of schizophrenia: The potential for neuroprotection
Lieberman, Jeffrey A; Malaspina, Dolores; Jarskog, L. Fredrik
2006 ;13(4):1-15 Apr, Primary Psychiatry
Schizophrenia, which has both genetic and environmental causes, is associated with persistent symptoms and severe functional disability. The illness lies dormant during the premorbid phase and begins to express itself during adolescence or early adulthood. Clinical progression and deterioration reaches a plateau in which the patient is said to be in the chronic phase of illness and at which point restoration of prior functioning is unlikely. The severe deficits associated with schizophrenia are often the result of progression of illness due to lack of appropriate treatment. However, recent advances in neuropsychiatry have led to very early identification of individuals at risk for psychosis, even during the prodromal stage when psychosis has not yet manifested clinically. While research has demonstrated that the efficacy of antipsychotics is limited when used during the chronic phase of illness, these medications can effectively control symptoms and prevent progression of illness when used during the early stages of illness. The evidence of neural degeneration in the pathophysiology of schizophrenic illness suggests that there may be treatment opportunities through neural protection. Neuroprotection, which refers to treatment that helps maintain central nervous system functionality in response to neurobiologic stress, may be responsible for prevention of disease progression and deterioration. In this monograph, Jeffrey L. Lieberman, MD, introduces the phases of schizophrenic illness in relation to the concepts of progression and deterioration. Next, Dolores Malaspina, MD, reviews the neurodevelopmental and neurodegenerative components of schizophrenia. Finally, L. Fredrik Jarskog, MD, focuses on the neuroprotective aspects of therapeutic interventions in schizophrenia. (journal abstract)
— id: 69126, year: 2006, vol: 13, page: 1, stat: Journal Article,

Schizophrenia: a neurodevelopmental or a neurodegenerative disorder
Malaspina, Dolores
2006 Aug;67(8):e07-e07, Journal of clinical psychiatry
The functional decline and onset of psychosis that individuals with schizophrenia experience suggests that schizophrenia has a neurodegenerational origin. However, current research favors a neurodevelopmental model in which individuals with schizophrenia develop abnormalities during brain development. The abnormality that leads to psychosis and deterioration remains latent as the brain develops but emerges concurrently with the brain's normal development or after an outside event that leads to changes in brain function. Prenatal adversity may underlie the neurodevelopmental process and neurodegeneration of schizophrenia. Because psychosis may be a clinically identifiable marker of an underlying neuropathologic process associated with deterioration, the best way to treat the illness is to reduce the duration of untreated psychosis, aim for full remission of psychosis, and combine medication with other therapies
— id: 80985, year: 2006, vol: 67, page: e07, stat: Journal Article,

Advancing paternal age and autism
Reichenberg, Abraham; Gross, Raz; Weiser, Mark; Bresnahan, Michealine; Silverman, Jeremy; Harlap, Susan; Rabinowitz, Jonathan; Shulman, Cory; Malaspina, Dolores; Lubin, Gad; Knobler, Haim Y; Davidson, Michael; Susser, Ezra
2006 Sep;63(9):1026-1032, Archives of general psychiatry
CONTEXT: Maternal and paternal ages are associated with neurodevelopmental disorders. OBJECTIVE: To examine the relationship between advancing paternal age at birth of offspring and their risk of autism spectrum disorder (ASD). DESIGN: Historical population-based cohort study. SETTING: Identification of ASD cases from the Israeli draft board medical registry. PARTICIPANTS: We conducted a study of Jewish persons born in Israel during 6 consecutive years. Virtually all men and about three quarters of women in this cohort underwent draft board assessment at age 17 years. Paternal age at birth was obtained for most of the cohort; maternal age was obtained for a smaller subset. We used the smaller subset (n = 132 271) with data on both paternal and maternal age for the primary analysis and the larger subset (n = 318 506) with data on paternal but not maternal age for sensitivity analyses. MAIN OUTCOME MEASURES: Information on persons coded as having International Classification of Diseases, 10th Revision ASD was obtained from the registry. The registry identified 110 cases of ASD (incidence, 8.3 cases per 10 000 persons), mainly autism, in the smaller subset with complete parental age data. RESULTS: There was a significant monotonic association between advancing paternal age and risk of ASD. Offspring of men 40 years or older were 5.75 times (95% confidence interval, 2.65-12.46; P<.001) more likely to have ASD compared with offspring of men younger than 30 years, after controlling for year of birth, socioeconomic status, and maternal age. Advancing maternal age showed no association with ASD after adjusting for paternal age. Sensitivity analyses indicated that these findings were not the result of bias due to missing data on maternal age. CONCLUSIONS: Advanced paternal age was associated with increased risk of ASD. Possible biological mechanisms include de novo mutations associated with advancing age or alterations in genetic imprinting
— id: 69088, year: 2006, vol: 63, page: 1026, stat: Journal Article,

Etiological heterogeneity and intelligence test scores in patients with schizophrenia
Wolitzky, Rachel; Goudsmit, Nora; Goetz, Raymond R; Printz, David; Gil, Roberto; Harkavy-Friedman, Jill; Malaspina, Dolores
2006 Feb;28(2):167-177, Journal of clinical & experimental neuropsychology
Previous research has indicated that patients with a family history of schizophrenia show a greater degree of cognitive and neuropsychological impairment than patients without a family history. We examined the neurocognitive performance, using the WAIS-R, of 51 patients with a family history (familial) and 103 patients without a family history (sporadic) to determine if differences exist that may help to explain the heterogeneous neuropsychological profile of the illness. The family history groups did not differ with respect to gender, diagnosis, ethnicity, age, age of onset, education or duration of illness. Multivariate analyses, covarying for age of onset and education, showed the sporadic group performed significantly better than the familial group on the digit symbol and object assembly subtests, with a trend level difference in overall performance IQ score. Additionally, we identified significant gender differences in favor of males for full scale and verbal IQ, the information, digit span, block design, and arithmetic subtests, and at a trend level, the picture assembly subtest. The family history group differences reflect relative dysfunction in visual attention and scanning, visuomotor control, and spatial processing and reasoning. Overall, the results suggest that sporadic patients have better perceptual-organizational skills and faster speed of processing
— id: 69093, year: 2006, vol: 28, page: 167, stat: Journal Article,

A model of verbal memory impairments in schizophrenia: two systems and their associations with underlying cognitive processes and clinical symptoms
Brebion, Gildas; Gorman, Jack M; Malaspina, Dolores; Amador, Xavier
2005 Jan;35(1):133-142, Psychological medicine
BACKGROUND: In a broad cognitive study of schizophrenia we investigated the relationships of verbal memory impairments with cognitive underpinnings on the one hand, and clinical symptomatology on the other. The results have been reported in previous papers. In this paper we show how all these data could be integrated into a consistent pattern of associations. METHOD: Fifty schizophrenic patients underwent a cognitive battery including a verbal memory task with free recall and recognition, a source memory task, and tests of processing speed and selective attention. Ratings for positive, negative and depressive symptoms were available for 40 of the patients. RESULTS: A factorial analysis revealed a distinction between measures of memory efficiency and measures of memory errors. The system of memory efficiency was associated with processing speed and selective attention at the cognitive level, and with depression at the symptom level. The system of memory errors was assumed to be underlain by source-monitoring deficits. These memory errors were increased by positive symptoms and decreased by certain negative symptoms. CONCLUSIONS: All the measures drawn from various memory tasks could be integrated into a model describing their associations with cognitive underpinnings and clinical symptomatology. This model provides a heuristic for the cognitive and pharmacological treatments of verbal memory impairments in schizophrenia, as well as for the understanding of positive symptoms
— id: 69101, year: 2005, vol: 35, page: 133, stat: Journal Article,

Prodromal interventions for schizophrenia vulnerability: the risks of being "at risk"
Corcoran, Cheryl; Malaspina, Dolores; Hercher, Laura
2005 Mar 1;73(2-3):173-184, Schizophrenia research
Given the morbidity and difficulty of treating psychotic disorders, including schizophrenia, there has been a move toward identifying and treating adolescents and young adults who appear to be clinically at risk or 'prodromal' to psychosis. The field now has greater specificity in identification, with rates of 40-50% conversion to frank psychosis within 1-2 years. There is further evidence that medications and other treatments may have some efficacy for 'prodromal' patients, though with variable side effects. However, controversy remains about some of the inherent risks in prodromal research, such as medication exposure and stigma among false-positives. In this paper, we add to this discussion through an analysis of ethics in prodromal research from the more established field of predictive genetic testing. Issues are raised about the effects of information on patients, families, and institutions, as well as future insurability, the limits of confidentiality (as it relies on discretion of patients and families), the autonomy of minors with psychiatric symptoms, and even the risks for the true-positive patient
— id: 69103, year: 2005, vol: 73, page: 173, stat: Journal Article,

Psychotic disorders
Corcoran, Cheryl; McAllister, Thomas W; Malaspina, Dolores
Textbook of traumatic brain injury Washington, DC, US: American Psychiatric Publishing, Inc., 2005,
(from the chapter) An association between traumatic brain injuries (TBIs) and later serious psychopathology, including psychosis, has been observed since the nineteenth century. Early in the twentieth century, Adolf Meyer's 1904 paper on what he termed 'traumatic insanity' (Meyer 1904) gave credence to the idea that trauma to the brain could result in significant psychopathology, including psychosis. He also emphasized that many of his patients had preexisting psychiatric disturbances or family histories of psychiatric illness, or both. The establishment of an association between TBI and psychosis is important because it has implications for the prevention of psychotic disorders, and it may shed light on the pathophysiology of both psychosis and TBI. In fact, there is extensive evidence of such an association between TBI and psychosis, as psychotic symptoms are consistently found to occur more frequently in individuals who have had a TBI, and patients with psychotic disorders are consistently more likely to have had a prior TBI than the general population. In this chapter, we review 1) diagnostic issues in relation to TBI and psychotic illness, 2) follow-up studies of psychosis in individuals who have incurred TBI (with an examination of factors that may predict later psychosis after TBI), 3) assessments of rates of premorbid TBI in patients with psychosis (with a look at how these patient groups may differ), 4) similarities between psychotic disorders and TBI, 5) the neurobiology of TBI and how it might lead to psychosis, 6) vulnerable populations, and 7) assessment, treatment, and prevention strategies.
— id: 4118, year: 2005, vol: , page: 213, stat: Chapter,

Olfactory deficits, cognition and negative symptoms in early onset psychosis
Corcoran, Cheryl; Whitaker, Agnes; Coleman, Eliza; Fried, Jane; Feldman, Judith; Goudsmit, Nora; Malaspina, Dolores
2005 Dec 15;80(2-3):283-293, Schizophrenia research
BACKGROUND: Smell identification deficits (SID) are common in adult schizophrenia, where they are associated with negative symptoms and lower intelligence. However, smell identification has not been examined in adolescents with early onset psychosis, wherein diagnosis is often obscure, and there are few prognostic predictors. METHOD: We examined smell identification, diagnosis, neuropsychological performance and symptoms in 26 well characterized adolescents with early onset psychosis, age 11-17 years. RESULTS: SID existed in the sample and were more common in patients with schizophrenia and psychotic depression than in patients with psychosis NOS and bipolar disorder. As in adults, SID were significantly associated with greater negative symptoms and lower verbal IQ. However, the associations of verbal IQ (and other verbal tasks) to smell identification in this pediatric sample were explained by the relation of both of these types of variables to negative symptoms. CONCLUSIONS: SID existed across this sample of youths with psychotic disorder, and were specifically related to typical characteristics of schizophrenia, such as negative symptoms and lower intelligence, but not to features of bipolar disorder, such as grandiosity. SID is a characteristic of early onset psychosis that may be useful for prognostic purposes
— id: 69098, year: 2005, vol: 80, page: 283, stat: Journal Article,

Inadequate sleep as a risk factor for obesity: analyses of the NHANES I
Gangwisch, James E; Malaspina, Dolores; Boden-Albala, Bernadette; Heymsfield, Steven B
2005 Oct 1;28(10):1289-1296, Sleep
STUDY OBJECTIVES: Sleep deprivation has been hypothesized to contribute toward obesity by decreasing leptin, increasing ghrelin, and compromising insulin sensitivity. This study examines cross-sectional and longitudinal data from a large United States sample to determine whether sleep duration is associated with obesity and weight gain. DESIGN: Longitudinal analyses of the 1982-1984, 1987, and 1992 NHANES I Followup Studies and cross-sectional analysis of the 1982-1984 study. SETTING: Probability sample of the civilian noninstitutionalized population of the United States. PARTICIPANTS: Sample sizes of 9,588 for the cross-sectional analyses, 8,073 for the 1987, and 6,981 for the 1992 longitudinal analyses. MEASUREMENTS AND RESULTS: Measured weight in 1982-1984 and self-reported weights in 1987 and 1992. Subjects between the ages of 32 and 49 years with self-reported sleep durations at baseline less than 7 hours had higher average body mass indexes and were more likely to be obese than subjects with sleep durations of 7 hours. Sleep durations over 7 hours were not consistently associated with either an increased or decreased likelihood of obesity in the cross-sectional and longitudinal results. Each additional hour of sleep at baseline was negatively associated with change in body mass index over the follow-up period, but this association was small and statistically insignificant. CONCLUSIONS: These findings support the hypothesis that sleep duration is associated with obesity in a large longitudinally monitored United States sample. These observations support earlier experimental sleep studies and provide a basis for future studies on weight control interventions that increase the quantity and quality of sleep
— id: 69095, year: 2005, vol: 28, page: 1289, stat: Journal Article,

Delusions in individuals with schizophrenia: factor structure, clinical correlates, and putative neurobiology
Kimhy, David; Goetz, Ray; Yale, Scott; Corcoran, Cheryl; Malaspina, Dolores
2005 Nov-Dec;38(6):338-344, Psychopathology
BACKGROUND: Delusions are a central feature of schizophrenia, yet our understanding of their neurobiology is limited. Attempt to link dimensions of psychopathology to putative neurobiological mechanisms depends on careful delineation of symptoms. Previous factor analytic studies of delusions in schizophrenia were limited by several methodological problems, including the use of patients medicated with antipsychotics, inclusion of nondelusion symptoms in the analyses, and/or inclusion of patients with psychotic disorders other than schizophrenia. These problems may have possibly biased the resulting factor structure and contributed to the inconclusive findings regarding the neurobiology of positive symptoms. Our goal is to examine the factor structure of delusions in antipsychotic-free individuals with diagnoses of schizophrenia/schizoaffective disorder. SAMPLING AND METHODS: We assessed 83 antipsychotic-free individuals with DSM-IV diagnoses of schizophrenia/schizoaffective disorder. A principal component analysis was conducted on the delusions symptoms of the SAPS. RESULTS: The principal component analysis resulted in three distinct and interpretable factors explaining 58.3% of the variance. The Delusions of Influence factor was comprised by delusions of being controlled, thought withdrawal, thought broadcasting, thought insertion, and mind reading. The Self-Significance Delusions factor was comprised by delusions of grandeur, reference, religious, and delusions of guilt/sin. The Delusions of Persecution factor was comprised solely by persecutory delusions. The three factors displayed distinct associations with hallucinations, bizarre behavior, attention, positive formal thought disorder, and avolition/apathy. CONCLUSIONS: The results indicate that delusions are best described by three distinct subtypes. The authors propose a novel model linking the three delusion subtypes, attributions to self/other, and putative neurobiological mechanisms. Implications for future research are discussed, as well as links to cognitive-behavioral conceptualizations of delusions
— id: 69096, year: 2005, vol: 38, page: 338, stat: Journal Article,

Paternal age and intelligence: implications for age-related genomic changes in male germ cells
Malaspina, Dolores; Reichenberg, Avi; Weiser, Mark; Fennig, Shmuel; Davidson, Michael; Harlap, Susan; Wolitzky, Rachel; Rabinowitz, Jonathan; Susser, Ezra; Knobler, Haim Y
2005 Jun;15(2):117-125, Psychiatric genetics
BACKGROUND: A robust association between advancing paternal age and schizophrenia risk is reported, and genetic changes in the germ cells of older men are presumed to underlie the effect. If that is so, then the pathway may include effects on cognition, as those with premorbid schizophrenia are reported to have lower intelligence. There are also substantial genetic influences on intelligence, so de novo genetic events in male germ cells, which accompany advancing paternal age, may plausibly influence offspring intelligence. OBJECTIVE: An association of paternal age with IQ in healthy adolescents may illuminate the mechanisms that link it to schizophrenia. METHOD: We examined the association of paternal age and IQ scores using the Israeli Army Board data on 44 175 individuals from a richly described birth cohort, along with maternal age and other potential modifiers. RESULTS: A significant inverted U-shaped relationship was observed between paternal age and IQ scores, which was independent from a similar association of IQ scores with maternal age. These relationships were not significantly attenuated by controlling for multiple possible confounding factors, including the other parent's age, parental education, social class, sex and birth order, birth weight and birth complications. Overall, parental age accounted for approximately 2% of the total variance in IQ scores, with later paternal age lowering non-verbal IQ scores more than verbal IQ scores. CONCLUSION: We found independent effects of maternal and paternal age on offspring IQ scores. The paternal age effect may be explained by de novo mutations or abnormal methylation of paternally imprinted genes, whereas maternal age may affect fetal neurodevelopment through age-related alterations in the in-utero environment. The influence of late paternal age to modify non-verbal IQ may be related to the pathways that increase the risk for schizophrenia in the offspring of older fathers
— id: 69100, year: 2005, vol: 15, page: 117, stat: Journal Article,

Nonlinear complexity and spectral analyses of heart rate variability in medicated and unmedicated patients with schizophrenia
Mujica-Parodi, L R; Yeragani, Vikram; Malaspina, Dolores
2005 ;51(1):10-15, Neuropsychobiology
OBJECTIVE: Heart rate variability (HRV) reflects functioning of the autonomic nervous system and possibly also regulation by the neural limbic system, abnormalities of which have both figured prominently in various etiological models of schizophrenia, particularly those that address patients' vulnerability to stress in connection to psychosis onset and exacerbation. This study provides data on cardiac functioning in a sample of schizophrenia patients that were either medication free or on atypical antipsychotics, as well as cardiac data on matched healthy controls. We included a medication-free group to investigate whether abnormalities in HRV previously reported in the literature and associated with atypical antipsychotics were solely the effect of medications or whether they might be a feature of the illness (or psychosis) itself. METHOD: We collected 24-hour ECGs on 19 patients and 24 controls. Of the patients, 9 were medication free and 10 were on atypical antipsychotics. All subject groups were matched for age and gender. Patient groups showed equivalent symptom severity and type, as well as duration of illness. We analyzed the data using nonlinear complexity (symbolic dynamic) HRV analyses as well as standard and relative spectral analyses. RESULTS: For the medication-free patients as compared to the healthy controls, our data show decreased R-R intervals during sleep, and abnormal suppression of all frequency ranges, but particularly the low frequency range, which persisted even after adjusting the spectral data for the mean R-R interval. This effect was exacerbated for patients on atypical antipsychotics. Likewise, nonlinear complexity analysis showed significantly impaired HRV for medication-free patients that was exacerbated in the patients on atypical antipsychotics. CONCLUSIONS: Altogether, the data suggest a pattern of significantly decreased cardiac vagal function of patients with schizophrenia as compared to healthy controls, apart from and beyond any differences due to medication side effects. The data additionally confirm earlier reports of a deleterious effect of atypical antipsychotics on HRV, which may exacerbate an underlying vulnerability in patients. These results support previous evidence that autonomic abnormalities may be a core feature of the illness (or psychosis), and that an even more conservative approach to cardiac risk in schizophrenia than previously thought may therefore be clinically appropriate
— id: 69104, year: 2005, vol: 51, page: 10, stat: Journal Article,

Lack of evidence for elevated obstetric complications in childhood onset schizophrenia
Ordonez, Anna E; Bobb, Aaron; Greenstein, Deanna; Baker, Natalie; Sporn, Alexandra; Lenane, Marge; Malaspina, Dolores; Rapaport, Judith; Gogtay, Nitin
2005 Jul 1;58(1):10-15, Biological psychiatry
BACKGROUND: Pre-, peri-, and postnatal obstetric complications (OC) are reported to be more frequent in adult patients with schizophrenia and have been linked to both greater severity and to 'earlier' age of onset (before either age 18 or 22) in studies of adult patients. We hypothesized that by extrapolation, patients with childhood-onset schizophrenia (COS), with very early onset and very severe illness, would have had more numerous or more salient OC compared with their healthy siblings. METHODS: We compared the obstetric records of 60 COS children and 48 healthy siblings using the Columbia Obstetrics Complication Scale, a comprehensive measurement scale consisting of 37 variables having included a separate scale for fetal hypoxia. RESULTS: Patients with COS did not have a higher incidence of OC than the healthy sibling control group with the exception of increased incidence of maternal vomiting. CONCLUSIONS: Obstetric complications, with the possible exception of maternal vomiting, are unlikely to play a major role in the etiopathogenesis of childhood-onset schizophrenia
— id: 69099, year: 2005, vol: 58, page: 10, stat: Journal Article,

Facial expressiveness in patients with schizophrenia compared to depressed patients and nonpatient comparison subjects
Tremeau, Fabien; Malaspina, Dolores; Duval, Fabrice; Correa, Humberto; Hager-Budny, Michaela; Coin-Bariou, Laura; Macher, Jean-Paul; Gorman, Jack M
2005 Jan;162(1):92-101, American journal of psychiatry
OBJECTIVE: Blunted affect is a major symptom in schizophrenia, and affective deficits clinically encompass deficits in expressiveness. Emotion research and ethological studies have shown that patients with schizophrenia are impaired in various modalities of expressiveness (posed and spontaneous emotion expressions, coverbal gestures, and smiles). Similar deficits have been described in depression, but comparative studies have brought mixed results. Our aim was to study and compare facial expressive behaviors related to affective deficits in patients with schizophrenia, depressed patients, and nonpatient comparison subjects. METHOD: Fifty-eight nondepressed inpatients with schizophrenia, 25 nonpsychotic inpatients with unipolar depression, and 25 nonpatient comparison subjects were asked to reproduce facial emotional expressions. Then the subjects were asked to speak about a specific emotion for 2 minutes. Each time, six cross-cultural emotions were tested. Facial emotional expressions were rated with the Facial Action Coding System. The number of facial coverbal gestures (facial expressions that are tied to speech) and the number of words were calculated. RESULTS: In relation to nonpatient comparison subjects, both patient groups were impaired for all expressive variables. Few differences were found between schizophrenia and depression: depressed subjects had less spontaneous expressions of other-than-happiness emotions, but overall, they appeared more expressive. Fifteen patients with schizophrenia were tested without and with typical or atypical antipsychotic medications: no differences could be found in study performance. CONCLUSIONS: The patients with schizophrenia and the patients with depression presented similar deficits in various expressive modalities: posed and spontaneous emotional expression, smiling, coverbal gestures, and verbal output
— id: 48726, year: 2005, vol: 162, page: 92, stat: Journal Article,

Sensitivity of ICD-10 diagnosis of psychotic disorders in the Israeli National Hospitalization Registry compared with RDC diagnoses based on SADS-L
Weiser, Mark; Kanyas, Kyra; Malaspina, Dolores; Harvey, Philip D; Glick, Ittai; Goetz, Deborah; Karni, Osnat; Yakir, Avi; Turetsky, Neil; Fennig, Shmuel; Nahon, Daniella; Lerer, Bernard; Davidson, Michael
2005 Jan-Feb;46(1):38-42, Comprehensive psychiatry
OBJECTIVE: The Israeli National Psychiatric Hospitalization Registry is a nationwide list of all psychiatric hospitalizations in the country and has been widely used as a source of data for psychiatric research. This study assessed the sensitivity of the diagnosis of psychotic disorders ( International Statistical Classification of Diseases, 10th Revision [ ICD-10 ] F20.0-F29.9) and schizophrenia ( ICD-10 F20.0-F20.9) in the Registry. METHOD: Registry discharge diagnoses of psychotic disorders ( ICD-10 F20.0-F29.9) and schizophrenia ( ICD-10 F20.0-F20.9) were compared with research diagnoses derived from best-estimate procedures based on Research Diagnostic Criteria (RDC) using structured clinical research interviews, hospital records, and family information. RESULTS: Out of 169 patients meeting RDC for psychotic disorder, 150 also had a diagnosis of psychotic disorders in the Registry, yielding a sensitivity of 0.89. Re-running this analysis for the narrow definition of schizophrenia identified 94 patients who were diagnosed with schizophrenia using RDC; 82 of those patients also had a diagnosis of schizophrenia in the Registry, yielding a sensitivity of 0.87. CONCLUSION: In 87% to 89% of cases with psychotic disorders or with schizophrenia, Registry diagnoses agreed with RDC diagnoses, a rate of agreement comparable with those of other, similar registries. Because a large number of analyses derived from this and similar national registries will be published in the coming years, this constitutes relevant information
— id: 69102, year: 2005, vol: 46, page: 38, stat: Journal Article,

Trail making and olfaction in schizophrenia: implications for processing speed
Goudsmit, Nora; Wolitzky, Rachel; Seckinger, Regine Anna; Corcoran, Cheryl; Stanford, Arielle; Rosenfield, Paul; Goetz, Ray; Malaspina, Dolores
2004 May;9(5):344-9, 356, CNS spectrums
BACKGROUND: Previous research has established a relationship between smell identification deficits (SID) and particular aspects of cognitive function among patients with schizophrenia. OBJECTIVE: To expand the extant literature, we examined the relationship between SID and the Trail Making Test to determine if processing speed is related to SID. METHODS: Our sample included 60 inpatients from the New York State Psychiatric Institute's Schizophrenia Research Unit. We considered age, deficit syndrome, verbal intelligence quotient, and education in our analyses due to their documented relationship to smell identification ability. RESULTS: Trails A errors and Trails A seconds accounted for a significant amount of the variance in University of Pennsylvania Smell Identification Test scores in a regression analysis (R2=.10, P=.008 and R2=.05, P=.04). CONCLUSION: Linking neurocognition to smell identification deficits may prove to be an essential marker for schizophrenia research
— id: 69112, year: 2004, vol: 9, page: 344, stat: Journal Article,

Resting neural activity distinguishes subgroups of schizophrenia patients
Malaspina, Dolores; Harkavy-Friedman, Jill; Corcoran, Cheryl; Mujica-Parodi, Lilianne; Printz, David; Gorman, Jack M; Van Heertum, Ronald
2004 Dec 15;56(12):931-937, Biological psychiatry
BACKGROUND: Schizophrenia is etiologically heterogeneous. It is anticipated, but unproven, that subgroups will differ in neuropathology and that neuroimaging may reveal these differences. The optimal imaging condition may be at rest, where greater variability is observed than during cognitive tasks, which more consistently reveal hypofrontality. We previously demonstrated symptom and physiologic differences between familial and sporadic schizophrenia patients and hypothesized that the groups would show different resting regional cerebral blood flow (rCBF) patterns. METHODS: Ten familial and sixteen sporadic schizophrenia patients and nine comparison subjects had single photon emission computed tomography imaging during passive visual fixation. Images were spatially normalized into Talairach coordinates and analyzed for group rCBF differences using SPM with a Z value threshold of 2.80, p < .001. RESULTS: The subgroups had similar age, gender, illness duration, and medication treatment. Sporadic patients had hypofrontality (anterior cingulate, paracingulate cortices, left dorsolateral and inferior-orbitofrontal), whereas familial patients had left temporoparietal hypoperfusion; all of these regions show resting activity in healthy subjects. Both groups hyperperfused the cerebellum/pons and parahippocampal gyrus; additional hyperperfusion for sporadic patients was observed in the fusiform; familial patients also hyperperfused the hippocampus, dentate, uncus, amygdala, thalamus, and putamen. CONCLUSIONS: Familial and sporadic schizophrenia patients had different resting rCBF profiles, supporting the hypothesis that certain subgroups have distinct neural underpinnings. Different neuropathologic processes among subgroups of schizophrenia patients may account for the prior contradictory results of resting imaging studies
— id: 69105, year: 2004, vol: 56, page: 931, stat: Journal Article,

The reliability and clinical correlates of figure-ground perception in schizophrenia
Malaspina, Dolores; Simon, Naomi; Goetz, Raymond R; Corcoran, Cheryl; Coleman, Eliza; Printz, David; Mujica-Parodi, Lilianne; Wolitzky, Rachel
2004 Summer;16(3):277-283, Journal of neuropsychiatry & clinical neurosciences
Schizophrenia subjects are impaired in a number of visual attention paradigms. However, their performance on tests of figure-ground visual perception (FGP), which requires subjects to visually discriminate figures embedded in a rival background, is relatively unstudied. We examined FGP in 63 schizophrenia patients and 27 control subjects and found that the patients performed the FGP test reliably and had significantly lower FGP scores than the control subjects. Figure-ground visual perception was significantly correlated with other neuropsychological test scores and was inversely related to negative symptoms. It was unrelated to antipsychotic medication treatment. Figure-ground visual perception depends on 'top down' processing of visual stimuli, and thus this data suggests that dysfunction in the higher-level pathways that modulate visual perceptual processes may also be related to a core defect in schizophrenia
— id: 69106, year: 2004, vol: 16, page: 277, stat: Journal Article,

Olfactory identification and WAIS-R performance in deficit and nondeficit schizophrenia
Seckinger, Regine Anna; Goudsmit, Nora; Coleman, Eliza; Harkavy-Friedman, Jill; Yale, Scott; Rosenfield, Paul J; Malaspina, Dolores
2004 Jul 1;69(1):55-65, Schizophrenia research
INTRODUCTION: An expanding database supports the notion that the deficit syndrome (DS) is a discrete condition within schizophrenia and recent data argues that Smell Identification Deficits (SID) may have a primary relationship with its pathophysiology. If so, then the relationship of University of Pennsylvania Smell Identification Test (UPSIT) scores with other neurocognitive measures in DS patients may point to the neural substrate of the deficit syndrome. METHOD: We examined the relationship of UPSIT scores and Wechsler Adult Intelligence Scale-Revised (WAIS-R) performance in 46 DSM-IV schizophrenia patients. The Schedule for the Deficit Syndrome (SDS) interview was used to subgroup the sample into 13 DS and 33 nondeficit syndrome (NDS) patients. RESULTS: DS and NDS groups had similar mean ages, age of onset, and GAF scores, but DS patients had fewer years of education. DS and NDS patients also did not differ in full scale, verbal or performance IQ or in any WAIS-R subtest. However, UPSIT scores were significantly worse in the DS patients, most of whom met criteria for a clinically meaningful olfactory impairment. In DS patients, UPSIT scores were significantly correlated with Performance IQ, Block Design, and Object Assembly, all of which are associated with complex visual-motor organizational function thought to be mediated by parietal circuitry. UPSIT scores in NDS patients were significantly related with Vocabulary, Similarities, and Digit Symbol subtests, which are indicative of verbal functioning. CONCLUSION: These preliminary data support previous findings suggesting that in addition to frontal neuropsychological abnormalities, DS patients may have greater performance impairments on tasks associated with parietal functioning. Our findings furthermore suggest that the parietal circuitry may be a conspicuous substrate for impaired odor identification ability in these patients. The lesser abnormalities in UPSIT ability in NDS patients may be attributed to verbal ability. These data are preliminary and further investigations with larger samples are needed to support our findings
— id: 69111, year: 2004, vol: 69, page: 55, stat: Journal Article,

A qualitative research study of the evolution of symptoms in individuals identified as prodromal to psychosis
Corcoran, Cheryl; Davidson, Larry; Sills-Shahar, Rachel; Nickou, Connie; Malaspina, Dolores; Miller, Tandy; McGlashan, Thomas
2003 Winter;74(4):313-332, Psychiatric quarterly
Because schizophrenia is difficult to treat and exacts large personal and societal costs, there is an effort underway to identify adolescents and young adults at high risk for psychosis. Theory-derived criteria of subthreshold positive symptoms identify a 'prodromal' or clinically at-risk population who have conversion rates to psychosis of 40 to 50% within one to two years. However, further characterization of the psychosis prodrome by qualitative research methods could increase the predictive value of the 'prodromal' designation. We conducted open-ended interviews with 20 parents of prodromal adolescents that focused on changes observed. The narratives fell into two thematically distinct subgroups, identified as 'declining' and 'never normal.' The prodromal adolescents described as 'declining' had a higher subsequent rate of conversion to psychosis than did the 'never normal' group. Although preliminary, these results suggest that a trajectory of change in personality, relationships, and behavior from an essentially normal baseline may be consistent with increased risk for psychosis among prodromal adolescents
— id: 69115, year: 2003, vol: 74, page: 313, stat: Journal Article,

The stress cascade and schizophrenia: etiology and onset
Corcoran, Cheryl; Walker, Elaine; Huot, Rebecca; Mittal, Vijay; Tessner, Kevin; Kestler, Lisa; Malaspina, Dolores
2003 ;29(4):671-692, Schizophrenia bulletin
Psychosocial stress is included in most etiologic models of schizophrenia, frequently as a precipitating factor for psychosis in vulnerable individuals. Nonetheless, the stress-diathesis model has not been tested prospectively in prodromal patients as a predictor of psychosis. The biological effects of stress are mediated by the hypothalamic-pituitary-adrenal (HPA) axis, which governs the release of steroids, including cortisol. The past few decades have witnessed an increased understanding of the neural effects of stress and cortisol, including both normal and abnormal diatheses. As few biological markers have been evaluated as risk factors for psychosis in prodromal patients, the HPA axis and its interaction with intervening life events are apt candidates for study. In this article, we review the HPA axis and its neural effects, present a model for how stress might precipitate psychosis in vulnerable individuals, review the empirical evidence of a link between stress and schizophrenia symptoms, and propose a research design and appropriate statistical models to test the stress-diathesis model for psychosis onset in prodromal patients
— id: 69114, year: 2003, vol: 29, page: 671, stat: Journal Article,

Anxiety and substance use comorbidity among inpatients with schizophrenia
Goodwin, Renee D; Amador, Xavier F; Malaspina, Dolores; Yale, Scott A; Goetz, Raymond R; Gorman, Jack M
2003 May 1;61(1):89-95, Schizophrenia research
OBJECTIVE: To determine the association between lifetime anxiety symptoms and anxiety disorders and substance use disorders among patients with schizophrenia. METHOD: Participants were 184 inpatients with schizophrenia at the Schizophrenia Research Unit (SRU) at the New York State Psychiatric Institute (NYSPI). Multivariate logistic regression analyses were used to determine the relationship between specific anxiety symptoms and anxiety disorders and substance use disorders among inpatients with schizophrenia. RESULTS: Anxiety symptoms and anxiety disorders were prevalent among 31.5% of the sample. Panic attacks were associated with a significantly increased odds (OR=7.4 (1.2, 47.1)) of comorbid alcohol or substance use disorders (lifetime). This association was specific to panic attacks and persisted after adjusting for differences in sociodemographic characteristics and comorbid anxiety symptoms and anxiety disorders. CONCLUSIONS: These findings are consistent with and extend previous data by providing evidence of an association between panic attacks and increased likelihood of substance use disorders among inpatients with schizophrenia. Future studies that determine the nature of this relationship, the sequence of symptom onsets, and examine whether treatment of anxiety can influence the onset or outcome associated with substance use are needed
— id: 69120, year: 2003, vol: 61, page: 89, stat: Journal Article,

A brief smell identification test discriminates between deficit and non-deficit schizophrenia
Goudsmit, Nora; Coleman, Eliza; Seckinger, Regine Anna; Wolitzky, Rachel; Stanford, Arielle D; Corcoran, Cheryl; Goetz, Raymond R; Malaspina, Dolores
2003 Sep 30;120(2):155-164, Psychiatry research
Evidence is accumulating that smell identification deficits (SID) and social dysfunction in schizophrenia may share a common pathophysiology. While most schizophrenia studies utilize the lengthy 40-item University of Pennsylvania Smell Identification Test (UPSIT) to assess smell identification ability, a brief 12-item smell identification test (B-SIT) has recently been constructed as a culturally neutral substitute for the UPSIT. By selecting the 12 items of the UPSIT from which the B-SIT was originally derived, we constructed a proxy for the B-SIT and compared the performance of 83 patients with schizophrenia to 69 normal subjects. We examined select properties of the B-SIT proxy in relation to the UPSIT to determine its efficacy for use in psychiatric populations. We considered the sensitivity of the B-SIT proxy and evaluated a cutoff score for identifying deficit syndrome schizophrenia (DS). The UPSIT and B-SIT proxy were significantly related in the patients (n=83, r=0.85, P=0.01) and in comparison subjects (n=69, r=0.83, P=0.01), and both measures similarly distinguished DS from non-deficit syndrome (non-DS) patients. The results of this study support the utility of the B-SIT for schizophrenia research and highlight the robustness of the relationship between SID and social dysfunction in schizophrenia
— id: 69117, year: 2003, vol: 120, page: 155, stat: Journal Article,

Suicide attempts in schizophrenia: the role of command auditory hallucinations for suicide
Harkavy-Friedman, Jill M; Kimhy, David; Nelson, Elizabeth A; Venarde, David F; Malaspina, Dolores; Mann, J John
2003 Aug;64(8):871-874, Journal of clinical psychiatry
BACKGROUND: We examined the presence of command auditory hallucinations for suicide (CAHS) in a sample of individuals with schizophrenia or schizoaffective disorder. We examined the relationship between CAHS and demographic and clinical variables. We also investigated the relationship between CAHS and suicide attempts. METHOD: 100 individuals with DSM-IV schizophrenia or schizoaffective disorder hospitalized on an inpatient research unit participated. Information was gathered using the Diagnostic Interview for Genetic Studies and the Harkavy Asnis Suicide Scale. Data were gathered from 1995 to 2001. RESULTS: CAHS were frequent in this sample (22%), as were suicide attempts (33%). Eight percent of the entire sample (36% of those who experienced CAHS) made at least 1 suicide attempt in response to the hallucinations. The presence of CAHS was not related to demographic or clinical measures assessed. The frequency of CAHS was not statistically different for suicide attempters (30%) and nonattempters (18%). However, 80% (8/10) of attempters with CAHS reported at least 1 attempt in response to CAHS. Three of 6 repeat attempters who made at least 1 suicide attempt in response to CAHS also made other attempts that were not in response to CAHS. The presence of CAHS was not associated with a history of depression or substance abuse/dependence. CONCLUSION: The presence of CAHS does not directly predict suicide attempts. However, individuals who are already at risk for suicidal behavior (e.g., past attempters) may be at increased risk for a suicide attempt when experiencing CAHS
— id: 69118, year: 2003, vol: 64, page: 871, stat: Journal Article,

Genome scan meta-analysis of schizophrenia and bipolar disorder, part II: Schizophrenia
Lewis, Cathryn M; Levinson, Douglas F; Wise, Lesley H; DeLisi, Lynn E; Straub, Richard E; Hovatta, Iiris; Williams, Nigel M; Schwab, Sibylle G; Pulver, Ann E; Faraone, Stephen V; Brzustowicz, Linda M; Kaufmann, Charles A; Garver, David L; Gurling, Hugh M D; Lindholm, Eva; Coon, Hilary; Moises, Hans W; Byerley, William; Shaw, Sarah H; Mesen, Andrea; Sherrington, Robin; O'Neill, F Anthony; Walsh, Dermot; Kendler, Kenneth S; Ekelund, Jesper; Paunio, Tiina; Lonnqvist, Jouko; Peltonen, Leena; O'Donovan, Michael C; Owen, Michael J; Wildenauer, Dieter B; Maier, Wolfgang; Nestadt, Gerald; Blouin, Jean-Louis; Antonarakis, Stylianos E; Mowry, Bryan J; Silverman, Jeremy M; Crowe, Raymond R; Cloninger, C Robert; Tsuang, Ming T; Malaspina, Dolores; Harkavy-Friedman, Jill M; Svrakic, Dragan M; Bassett, Anne S; Holcomb, Jennifer; Kalsi, Gursharan; McQuillin, Andrew; Brynjolfson, Jon; Sigmundsson, Thordur; Petursson, Hannes; Jazin, Elena; Zoega, Tomas; Helgason, Tomas
2003 Jul;73(1):34-48, American journal of human genetics
Schizophrenia is a common disorder with high heritability and a 10-fold increase in risk to siblings of probands. Replication has been inconsistent for reports of significant genetic linkage. To assess evidence for linkage across studies, rank-based genome scan meta-analysis (GSMA) was applied to data from 20 schizophrenia genome scans. Each marker for each scan was assigned to 1 of 120 30-cM bins, with the bins ranked by linkage scores (1 = most significant) and the ranks averaged across studies (R(avg)) and then weighted for sample size (N(sqrt)[affected casess]). A permutation test was used to compute the probability of observing, by chance, each bin's average rank (P(AvgRnk)) or of observing it for a bin with the same place (first, second, etc.) in the order of average ranks in each permutation (P(ord)). The GSMA produced significant genomewide evidence for linkage on chromosome 2q (PAvgRnk<.000417). Two aggregate criteria for linkage were also met (clusters of nominally significant P values that did not occur in 1,000 replicates of the entire data set with no linkage present): 12 consecutive bins with both P(AvgRnk) and P(ord)<.05, including regions of chromosomes 5q, 3p, 11q, 6p, 1q, 22q, 8p, 20q, and 14p, and 19 consecutive bins with P(ord)<.05, additionally including regions of chromosomes 16q, 18q, 10p, 15q, 6q, and 17q. There is greater consistency of linkage results across studies than has been previously recognized. The results suggest that some or all of these regions contain loci that increase susceptibility to schizophrenia in diverse populations
— id: 42337, year: 2003, vol: 73, page: 34, stat: Journal Article,

Olfaction and social drive in schizophrenia
Malaspina, Dolores; Coleman, Eliza
2003 Jun;60(6):578-584, Archives of general psychiatry
BACKGROUND: The neurobiology of social dysfunction in schizophrenia is unknown, but smell identification deficits (SIDs) exist in schizophrenia, and olfaction is related to social affiliation in other mammals. The SIDs have been linked with negative symptoms and the deficit syndrome, but any specificity of SIDs for social dysfunction is unstudied. Low intelligence might explain this relationship, if it is associated with both negative symptoms and SIDs. We examined whether SIDs in schizophrenia were related broadly to negative symptoms, as are a number of other neuropsychological measures, or whether they might show a more specific relationship with social drive. METHODS: Smell Identification Test scores, Wechsler Adult Intelligence Scale-Revised IQ, symptomatology assessed with the Positive and Negative Syndrome Scale, and the deficit syndrome were determined in 70 patients with DSM-IV schizophrenia. RESULTS: The SIDs were related to negative symptoms and the deficit syndrome, but the association of SIDs with diminished social drive explained both relationships. Smell identification was also related to Wechsler Adult Intelligence Scale-Revised IQ, but intelligence was independent of the relationship of SID and social drive. The worse Smell Identification Test scores in male patients were attributable to a greater preponderance of men with the deficit syndrome. CONCLUSIONS: These analyses demonstrated independent relationships of Smell Identification Test scores to social drive and intelligence that together accounted for almost 50% of the variance in Smell Identification Test scores. There may be common neural substrates for the low social drive and SIDs in schizophrenia
— id: 69119, year: 2003, vol: 60, page: 578, stat: Journal Article,

Using figure ground perception to examine the unitary and heterogeneity models for psychopathology in schizophrenia
Malaspina, Dolores; Simon, Naomi; Corcoran, Cheryl; Mujica-Parodi, Lillian; Goetz, Raymond R; Gorman, Jack
2003 Feb 1;59(2-3):297-299, Schizophrenia research
— id: 69121, year: 2003, vol: 59, page: 297, stat: Journal Article,

The concept of population prevention: application to schizophrenia
Mojtabai, Ramin; Malaspina, Dolores; Susser, Ezra
2003 ;29(4):791-801, Schizophrenia bulletin
There is currently a debate about the appropriate approach to prevention of schizophrenia. While many argue that prevention efforts should focus on individuals at high risk of developing the illness, others argue for interventions that would reduce the risk in the whole population. This article situates the debate in a historical context. We find its antecedents in a classic 1940s and 1950s debate between British physicians George Pickering and Robert Platt on hypertension and trace a line from Pickering to the influential concept of population prevention formulated by his student Geoffrey Rose. We then discuss the potential application of population prevention to schizophrenia. The article concludes that population and high-risk prevention strategies can be complementary and that it may be feasible and appropriate to use them in combination
— id: 69113, year: 2003, vol: 29, page: 791, stat: Journal Article,

Weight Gain in Bipolar Disorder: Causes and Treatments
Printz, David; Clark, Joy; Stricks, Laurie; Malaspina, Dolores
2003 ;10(11):29-33,, Primary Psychiatry
Bipolar disorder is associated with a high incidence of significant obesity, much of which is likely iatrogenic and caused by mood-stabilizing medications. This obesity produces a significant psychosocial burden, increases the risk for a range of comorbid medical disorders, and leads to higher rates of medication noncompliance and clinical relapse. Fortunately, the range of mood-stabilizing agents is expanding and several of the newer agents have a lower tendency to promote weight gain. Also, a greater focus on medication-associated weight gain has increased the data available to aid in medication selection. This article summarizes epidemiologic data relating obesity to bipolar illness, describe the associations between specific mood stabilizers and weight gain, and provide practical approaches to the management of weight gain in bipolar patients. (journal abstract)
— id: 69127, year: 2003, vol: 10, page: 29, stat: Journal Article,

Corticotropin-releasing factor in posttraumatic stress disorder (PTSD) with secondary psychotic symptoms, nonpsychotic PTSD, and healthy control subjects
Sautter, Frederic J; Bissette, Garth; Wiley, Justin; Manguno-Mire, Gina; Schoenbachler, Benjamin; Myers, Leann; Johnson, Janet E; Cerbone, Arleen; Malaspina, Dolores
2003 Dec 15;54(12):1382-1388, Biological psychiatry
BACKGROUND: Recent studies have reported a high comorbidity between posttraumatic stress disorder (PTSD) and psychotic symptoms, and it has been hypothesized that PTSD with comorbid psychosis is a severe form of PTSD. Few studies have examined the neurobiology of PTSD with comorbid psychosis. If PTSD with secondary psychotic symptoms (PTSD-SP) is a severe form of PTSD, then it might be expected to show more extreme perturbations in the neuroendocrine patterns that characterize PTSD. METHODS: Patients with PTSD with secondary psychotic symptoms (PTSD-SP), PTSD without psychosis, and healthy comparison subjects were compared for differences in cerebrospinal fluid concentrations of corticotropin-releasing factor (CRF) and somatotropin-release-inhibiting hormone (SRIF). RESULTS: The PTSD-SP subjects had significantly higher mean levels of CRF than either the PTSD or control subjects (p <.01). The three groups showed similar SRIF levels. CONCLUSIONS: These data implicate abnormalities in the secretion of CRF with the production of secondary psychotic symptoms in PTSD. This finding supports the validity of PTSD-SP as a PTSD subtype and as a severe form of PTSD
— id: 69116, year: 2003, vol: 54, page: 1382, stat: Journal Article,

Source monitoring impairments in schizophrenia: characterisation and associations with positive and negative symptomatology
Brebion, Gildas; Gorman, Jack M; Amador, Xavier; Malaspina, Dolores; Sharif, Zafar
2002 Sep 15;112(1):27-39, Psychiatry research
This article describes a consistent pattern of the associations between source monitoring failure and clinical symptomatology in schizophrenia. The associations with positive symptoms in this sample have been reported previously, but not the associations with negative symptoms. Forty patients with schizophrenia were administered several memory tasks including free recall of lists of words, recognition and source memory. Various memory errors assumed to stem from source monitoring failure were derived. They include intrusions and recall of words from previous lists in free recall, false recognitions, and confusion with regard to the source of the stimuli. We studied the associations of these memory errors with positive symptoms and with a broad range of negative symptoms. All the memory errors were positively associated with at least one positive symptom. On the other hand, these errors were inversely associated with certain negative symptoms reflecting lack of emotion or lack of social interactions. Thus positive and negative symptomatology appear to have opposite links to the source monitoring errors observed in patients with schizophrenia. Cognitive mechanisms leading to different types of source monitoring errors and possibly to the formation of positive symptoms are discussed
— id: 69122, year: 2002, vol: 112, page: 27, stat: Journal Article,

Paternal age and risk of schizophrenia in adult offspring
Brown, Alan S; Schaefer, Catherine A; Wyatt, Richard J; Begg, Melissa D; Goetz, Raymond; Bresnahan, Michaeline A; Harkavy-Friedman, Jill; Gorman, Jack M; Malaspina, Dolores; Susser, Ezra S
2002 Sep;159(9):1528-1533, American journal of psychiatry
OBJECTIVE: The study examined the relation between paternal age at the time of birth and risk of schizophrenia in the adult offspring. METHOD: Data from the birth cohort of the Prenatal Determinants of Schizophrenia study were used in this study. Virtually all members of this birth cohort had prospective information about paternal age at the time of the offspring's birth. Subjects with schizophrenia and other schizophrenia spectrum disorders (N=71) among members of this birth cohort were previously ascertained. In separate analyses, paternal age was modeled as a continuous variable and as a categorical variable, and its relation with the risk of adult schizophrenia and other schizophrenia spectrum disorders and with the risk of schizophrenia separately were examined. RESULTS: There was a marginally significant, monotonic association between advancing paternal age and risk of adult schizophrenia and schizophrenia spectrum disorders. The association held after the analysis controlled for the effects of maternal age and other potential confounders. Similar results were observed when only subjects with schizophrenia were included in the analysis. CONCLUSIONS: Advanced paternal age at the time of birth of the offspring may be a risk factor for adult schizophrenia
— id: 69123, year: 2002, vol: 159, page: 1528, stat: Journal Article,

Odor identification impairments in schizophrenia: relationship with demographic measures, clinical variables, and diagnostic subtypes
Coleman, Eliza; Goetz, Raymond R; Leitman, David; Yale, Scott; Stanford, Ariel; Gorman, Jack M; Malaspina, Dolores
2002 Jan;7(1):43-48, CNS spectrums
Smell identification deficits are consistently found in schizophrenia (SZ), but little is known about the nature and characterization of this deficit or its relationship to the phenomenology of the illness. This study aims to further delineate smell identification errors in SZ by examining the relationship of patient demographic differences with smell-identification performance. Our results showed that a patient's gender and education were related to odor-identification scores, with better performance seen in female patients and in those with greater educational attainment. However, there was no effect related to age, ethnicity, or socioeconomic status on odor identification. A smell identification deficit was also unrelated to clinical characteristics of the patients, including age at first hospitalization, number of psychiatric hospitalizations, and duration of illness. Odor identification also did not differ by SZ subtype, nor between SZ and schizoaffective disorder patients. These findings emphasize that odor identification deficits in SZ are unrelated to clinical illness features, cannot be explained by other confounds related to olfaction in the general population, and may be core features related to the SZ disease process
— id: 69109, year: 2002, vol: 7, page: 43, stat: Journal Article,

Could stress cause psychosis in individuals vulnerable to schizophrenia?
Corcoran, Cheryl; Mujica-Parodi, Lilianne; Yale, Scott; Leitman, David; Malaspina, Dolores
2002 Jan;7(1):33-8, 41, CNS spectrums
It has long been considered that psychosocial stress plays a role in the expression of symptoms in schizophrenia (SZ), as it interacts with latent neural vulnerability that stems from genetic liability and early environmental insult. Advances in the understanding of the neurobiology of the stress cascade in both animal and human studies lead to a plausible model by which this interaction may occur: through neurotoxic effects on the hippocampus that may involve synaptic remodeling. Of late, the neurodevelopmental model of SZ etiology has been favored. But an elaboration of this schema that credits the impact of postnatal events and considers a role for neurodegenerative changes may be more plausible, given the evidence for gene-environment interaction in SZ expression and progressive structural changes observed with magnetic resonance imaging. Furthermore, new insights into nongliotic neurotoxic effects such as apoptosis, failure of neurogenesis, and changes in circuitry lead to an expansion of the time frame in which environmental effects may mediate expression of SZ symptoms
— id: 69110, year: 2002, vol: 7, page: 33, stat: Journal Article,

Paternal age and preeclampsia
Harlap, Susan; Paltiel, Ora; Deutsch, Lisa; Knaanie, Ariella; Masalha, Sausan; Tiram, Efrat; Caplan, Lee S; Malaspina, Dolores; Friedlander, Yechiel
2002 Nov;13(6):660-667, Epidemiology
BACKGROUND: Paternal aging is associated with premeiotic damage to spermatogonia, a mechanism by which new point mutations are introduced into the gene pool. We hypothesized that paternal age might contribute to preeclampsia. METHODS: We studied the incidence of preeclampsia in 81,213 deliveries surveyed in 1964-1976 in the Jerusalem Perinatal Study. We controlled for maternal age, parity and other risk factors using logistic regression. RESULTS: Preeclampsia was reported in 1303 deliveries (1.6%). Compared with fathers age 25-34 years, the odds ratios (ORs) for preeclampsia were 1.24 (95% confidence interval = 1.05-1.46) for age 35-44 and 1.80 (1.40-2.31) for age 45+. For fathers age <25, the OR was 1.25 (1.04-1.51). Although weaker than maternal age effects, paternal effects were consistent within subgroups of other variables. CONCLUSIONS: These findings support the hypothesis that a modest proportion of preeclampsia might be explained by new mutations acquired from fathers and add to a growing body of evidence for paternal age effects in birth defects, neuropsychiatric disease and neoplasia
— id: 39378, year: 2002, vol: 13, page: 660, stat: Journal Article,

Schizophrenia risk and paternal age: a potential role for de novo mutations in schizophrenia vulnerability genes
Malaspina, Dolores; Brown, Alan; Goetz, Deborah; Alia-Klein, Nelly; Harkavy-Friedman, Jill; Harlap, Susan; Fennig, Shmuel
2002 Jan;7(1):26-29, CNS spectrums
How schizophrenia (SZ) is maintained at roughly 1% of the population despite diminished reproduction is one puzzle currently facing researchers. De novo mutations were first proposed over half a century ago as a source for new SZ genes. Current evidence linking advancing paternal age to SZ risk makes revisiting this hypothesis important. Advancing paternal age is the major source of new mutations in the human population. This article will examine potential mechanisms whereby parental age may impact new mutations, as well as review recent data supporting such a hypothesis
— id: 44876, year: 2002, vol: 7, page: 26, stat: Journal Article,

Odor identification, eye tracking and deficit syndrome schizophrenia
Malaspina, Dolores; Coleman, Eliza; Goetz, Raymond R; Harkavy-Friedman, Jill; Corcoran, Cheryl; Amador, Xavier; Yale, Scott; Gorman, Jack M
2002 May 15;51(10):809-815, Biological psychiatry
BACKGROUND: Deficit syndrome (DS) schizophrenia patients have smooth pursuit eye movement (SPEM) dysfunction. We examined if they also had smell identification deficits, since social affiliation is related to olfaction in other mammals. METHODS: Sixty-seven patients had DS assessments: 31 patients had SPEM and 50 had Smell Identification Test (SIT) assessments, and 14 patients had both measurements. RESULTS: DS patients had worse SPEM and SIT performance than the non-DS patients. Areas under the receiver-operator characteristic (ROC) curves for SIT and SPEM were both fairly accurate in identifying the DS. The odds ratio (OR) for the DS for impaired versus normal SPEM was 6.21 (95% confidence interval [CI]: 1.21, 32.25) and for microsmia versus normosmia was 10.4 (95% CI: 1.23, 88.18). Further analyses showed that the association of SIT with both SPEM and the DS could account for the SPEM-DS association. CONCLUSIONS: We found a strong association between the DS and SIT scores suggesting that the neural substrates of olfaction may be related to social affiliation in humans, as they are in other mammals. These data further support the notion that the DS defines a homogeneous subgroup of schizophrenia patients and further suggest that dysfunction in the neural circuitry of olfaction may contribute to its pathophysiology
— id: 69124, year: 2002, vol: 51, page: 809, stat: Journal Article,

Paternal age and sporadic schizophrenia: evidence for de novo mutations
Malaspina, Dolores; Corcoran, Cheryl; Fahim, Cherine; Berman, Ariela; Harkavy-Friedman, Jill; Yale, Scott; Goetz, Deborah; Goetz, Raymond; Harlap, Susan; Gorman, Jack
2002 Apr 8;114(3):299-303, American journal of medical genetics
Schizophrenia is an etiologically heterogeneous syndrome. It has a strong genetic component and exists in clinically indistinguishable familial and nonfamilial (sporadic) forms. A significant role for de novo genetic mutations in genetic schizophrenia vulnerability is suggested by a strong monotonic increase in schizophrenia risk with advancing paternal age. However, an alternative explanation for the paternal age effect in schizophrenia is that childbearing is delayed in fathers who themselves have genetic schizophrenia vulnerability. In this study, we compared paternal birth ages between patient groups with familial (n = 35) and sporadic (n = 68) patients with DSM-IV schizophrenia from an inpatient schizophrenia research unit. If later age of fathering children is related to having some genetic schizophrenia vulnerability, then paternal birth age should be later in familial schizophrenia cases than in sporadic cases, and any association of father's age and schizophrenia risk in offspring would be a spurious finding, unrelated to etiology. However, if de novo mutations cause sporadic schizophrenia, then patients without a family history of schizophrenia would have older fathers than familial patients. We found that patients without a family history of schizophrenia had significantly older fathers (4.7 years) than familial patients; so later childbirth was not attributable to parental psychiatric illness. These findings support the hypothesis that de novo mutations contribute to the risk for sporadic schizophrenia
— id: 69125, year: 2002, vol: 114, page: 299, stat: Journal Article,

Epidemiologic and genetic aspects of neuropsychiatric disorders
Malaspina, Dolores; Corcoran, Cheryl; Hamilton, Steven P
The American psychiatric publishing textbook of neuropsychiatry and clinical neurosciences (4th ed.) Washington, DC, US: American Psychiatric Publishing, Inc., 2002,
(from the chapter) Focuses on some of the findings of statistical genetics, genetic epidemiology, and molecular methodology in the study of neuropsychiatric disorders.
— id: 4119, year: 2002, vol: , page: 323, stat: Chapter,

Low heart rate variability is not caused by typical neuroleptics in schizophrenia patients
Malaspina, Dolores; Dalack, Gregory; Leitman, David; Corcoran, Cheryl; Amador, Xavier F; Yale, Scott; Glassman, Alexander; Gorman, Jack M
2002 Jan;7(1):53-57, CNS spectrums
Both elevated cardiovascular mortality and low cardio-vagal (parasympathetic) heart rate variability (HRV)--a risk factor for postmyocardial infarction--are reported in schizophrenia (SZ). Since a number of medications have strong effects of cardiac conductivity, we thought it important to examine if typical neuroleptic medications might also affect HRV. We examined cardiac vagal activity during both neuroleptic treatment and a drug-free condition in seven SZ patients who were participating in a pilot double-blind, crossover study of placebo and haloperidol treatment. Twenty-four-hour Holter electrocardiograms were analyzed for high frequency HRV, quantitated as the percent of successive normal interbeat intervals greater than 50 milliseconds (PNN50), which is a good index of parasympathetic cardiac modulation. The patients showed unchanged PNN50 (8.4+/-9.5 versus 8.3+/-10.5; t=.22, df=6, P=.5) between the haloperidol treatment and drug-free conditions. Despite the elapsed time, change in medication, and altered clinical state, the PNN50s were highly correlated (Spearman r=.98, P=.000). SAPS positive symptom scores declined with treatment from 12.8+/-6.5 to 8.5+/-3.5; paired t=3.26: df=6; P=.01. PNN50s were significantly associated with positive (r=-.86, df=6, P=.012) and negative symptom scores (r=-.87, df=6, P=.01). We found low cardiovagal modulation in medication-free SZ patients that was associated with core SZ symptoms and was unchanged by haloperidol and benztropine treatment. The reduced HRV in SZ patients at baseline may render them at greater cardiovascular risk than healthy subjects when treated with medications having strong cardiovascular effects
— id: 69108, year: 2002, vol: 7, page: 53, stat: Journal Article,

Are cognitive symptoms of schizophrenia mediated by abnormalities in emotional arousal?
Mujica-Parodi, Lilianne R; Corcoran, Cheryl; Greenberg, Tsafrir; Sackeim, Harold A; Malaspina, Dolores
2002 Jan;7(1):58-60, 65, CNS spectrums
We tested 28 individuals with schizophrenia (SZ) and 16 healthy individuals on a test of logical reasoning and 'cognitive gating,' defined as the ability to discriminate between relevant and irrelevant information in confirming or disconfirming a given belief. The Logical Reasoning and Cognitive Gating Task tests both processes under neutral and affect-laden conditions. This is done by presenting formally identical constructs using benign and emotionally arousing language. When separated by symptom profiles, we found statistically significant differences for performance and arousal response between patients with delusions, patients with formal thought disorder, and patients with neither delusions nor formal thought disorder, as well as between patients and healthy controls. When analyzed by error type, we found that nearly all errors by delusional patients were caused by overly restrictive information choice, a pattern that may be related to a delusional patient's tendency to 'jump to conclusions' on Bayesian probabilistic tasks. This is in contrast to patients with formal thought disorder, whose low performance resulted also from overly extensive information choice. The tendencies towards restriction were exacerbated by arousal, which is consistent with studies on cognition and arousal in healthy individuals. After briefly examining research on emotional arousal and SZ, and the interaction between emotional arousal and restriction of perceptual cues in healthy individuals, we conclude by suggesting a model which accounts for the distinctive cognitive characteristics of delusional patients by their possessing distinct vulnerabilities to emotional arousal. Specifically, these results suggest the possibility that delusional patients process information in a manner that is essentially intact. However, delusional patients may possess an acute vulnerability to emotional arousal that might cause delusional individuals to behave cognitively as if they were healthy individuals under significantly more severe forms of stress
— id: 69107, year: 2002, vol: 7, page: 58, stat: Journal Article,

Clinical and cognitive factors associated with verbal memory task performance in patients with schizophrenia
Brebion, G; Gorman, J M; Malaspina, D; Sharif, Z; Amador, X
2001 May;158(5):758-764, American journal of psychiatry
OBJECTIVE: The authors have previously shown the role of depression, slowing of processing speed, and selective attention deficit in verbal memory task performance in schizophrenia. They wished to determine the specific contribution of each of these factors to various types of memory impairment. METHOD: The negative symptom score from the Positive and Negative Syndrome Scale, the Hamilton Depression Rating Scale score, a measure of processing speed, and a measure of selective attention were entered as predictors in regression analyses. Furthermore, analyses of covariance were conducted on the memory measures to test the significance of the differences between schizophrenic patients and healthy comparison subjects after control for processing speed and selective attention. RESULTS: Depression was associated only with deep encoding reflected by semantic clustering. Selective attention was associated only with superficial encoding reflected by serial recall. Slowing of processing speed was associated with both deep and superficial encoding. Negative symptoms were not associated with memory impairment except for the avolition item from the Scale for the Assessment of Negative Symptoms. Processing speed accounted for all the group differences on the memory measures that reflected superficial encoding. In addition, a subgroup of patients with no or minor depression was not significantly impaired on deep encoding relative to the healthy comparison group. CONCLUSIONS: The authors suggest that verbal memory impairment in schizophrenia is a consequence of depression and slowness, rather than a primary feature of the disease
— id: 69138, year: 2001, vol: 158, page: 758, stat: Journal Article,

A.E. Bennett Research Award. Prenatal rubella, premorbid abnormalities, and adult schizophrenia
Brown, A S; Cohen, P; Harkavy-Friedman, J; Babulas, V; Malaspina, D; Gorman, J M; Susser, E S
2001 Mar 15;49(6):473-486, Biological psychiatry
BACKGROUND: Premorbid neurocognitive, neuromotor, and behavioral function tends to be disturbed in schizophrenia. We previously demonstrated that a birth cohort clinically and serologically documented with prenatal rubella evidenced a marked increase in risk of nonaffective psychosis. In our study, we examined whether rubella-exposed subjects destined to develop schizophrenia and other schizophrenia spectrum disorders (SSD), compared with exposed control subjects, had greater impairment in several premorbid functions. METHODS: Subjects were interviewed using a direct, comprehensive research assessment and diagnosed by consensus. We compared the degree of IQ decline, as well as premorbid neuromotor and behavioral dysfunction, between rubella-exposed subjects who developed schizophrenia spectrum psychosis (SSP) and exposed control subjects from the cohort. We also compared the gestational timing of rubella infection between the cases and control subjects. RESULTS: This rubella-exposed birth cohort evidenced a markedly increased risk of SSD (20.4% or 11/53). Rubella-exposed SSP cases, compared with rubella-exposed control subjects, demonstrated a decline in IQ from childhood to adolescence, and increased premorbid neuromotor and behavioral abnormalities. Moreover, it appears that early gestational rubella exposure may represent a period of increased vulnerability for SSD. CONCLUSIONS: These findings link a known prenatal exposure, a deviant neurodevelopmental trajectory in childhood and adolescence, and SSP in adulthood within the same individuals
— id: 69139, year: 2001, vol: 49, page: 473, stat: Journal Article,

Event-related potentials in schizophrenia during tonal and phonetic oddball tasks: relations to diagnostic subtype, symptom features and verbal memory
Bruder, G E; Kayser, J; Tenke, C E; Friedman, M; Malaspina, D; Gorman, J M
2001 Sep 15;50(6):447-452, Biological psychiatry
BACKGROUND: This study compares event-related potentials for paranoid patients (n = 13) versus matched undifferentiated patients and unmedicated patients (n = 14) versus matched healthy adults. METHODS: Event-related potentials of right-handed patients and control subjects were recorded from 30 electrodes during oddball tasks using consonant-vowel syllables or complex tones. Patients were also assessed using the Positive and Negative Syndrome Scale, the Thought Disorder Index, and the Wechsler Memory Scale. RESULTS: Paranoid patients did not differ from undifferentiated patients in N1 or P3 amplitude but showed larger N2 at frontocentral sites to phonetic stimuli, as well as larger N2 over left than right hemisphere. Unmedicated patients showed reduced N2, but not N1 or P3, compared to control subjects. CONCLUSIONS: The N2 findings are consistent with neuropsychological evidence of greater verbal abilities and left hemisphere dominance in paranoid than nonparanoid schizophrenia. The findings also confirm the relationship of P3 to total Brief Psychiatric Rating Scale score, negative symptoms, and verbal associative memory
— id: 69136, year: 2001, vol: 50, page: 447, stat: Journal Article,

The neurobiology of the stress cascade and its potential relevance for schizophrenia
Corcoran, Cheryl; Gallitano, Amelia; Leitman, David; Malaspina, Dolores
2001 ;7(1):3-14 Jan, Journal of psychiatric practice
This review explores the neurobiology of stress and its possible role in the etiology of schizophrenia. Major life events may play a role in onset and relapse in schizophrenia. Other data suggest that early stress exposure increases schizophrenia risk, especially in individuals with latent vulnerability. Animal research has led to an elucidation of the mechanisms by which stress and cortisol are toxic to the hippocampus and impair cognition. Associations among these factors have been found in a variety of human conditions, including psychiatric illness and normal aging. These mechanisms are plausible in schizophrenia, which is characterized by a degree of cortisol dysregulation, hippocampal abnormality, and cognitive impairment. Characterization of the role of the stress cascade in schizophrenia has implications for novel pharmacologic and other treatment, especially for cognitive symptoms, which are debilitating and largely refractory to treatment.
— id: 69128, year: 2001, vol: 7, page: 3, stat: Journal Article,

Traumatic brain injury and risk for schizophrenia
Corcoran, Cheryl; Malaspina, Dolores
2001 ;30(1):17-32 Spr, International journal of mental health
It has been argued that schizophrenia following traumatic brain injury (TBI) may be a phenocopy of genetic schizophrenia. But since many of those with post-TBI psychosis have a family history of schizophrenia or pre-injury personalities similar to prodromal schizophrenia, the association between TBI and schizophrenia may also indicate gene-environment synergy or, alternatively, TBI and schizophrenia may be spuriously associated. Using models/hypotheses that examined joint and separate effects of genes and TBI on risk for schizophrenia, the authors estimated a conservative attributable risk of schizophrenia following TBI at 1% of cases of schizophrenia. An analysis of published data yielded a more liberal estimate of 17%. TBI may account for a small proportion of schizophrenia risk; but in light of the devastation the disorder causes, this risk may be considered appreciable.
— id: 69129, year: 2001, vol: 30, page: 17, stat: Journal Article,

Linkage disequilibrium for schizophrenia at the chromosome 15q13-14 locus of the alpha7-nicotinic acetylcholine receptor subunit gene (CHRNA7)
Freedman, R; Leonard, S; Gault, J M; Hopkins, J; Cloninger, C R; Kaufmann, C A; Tsuang, M T; Farone, S V; Malaspina, D; Svrakic, D M; Sanders, A; Gejman, P
2001 Jan 8;105(1):20-22, American journal of medical genetics
The transmission/disequilibrium test was used for fine mapping of the linkage of schizophrenia to the chromosome 15q13-14 region, the site of a candidate gene, the alpha7 nicotinic acetylcholine receptor subunit gene (CHRNA7), in parent-child triads from the NIMH Schizophrenia Genetics Initiative families. This candidate gene was identified from neurobiological studies of deficits in schizophrenics of the inhibitory gating of the P50 auditory evoked potential. The neurobiological deficit was also used as a phenotype for subsequent linkage analysis. In the present study, significant genotype-wise disequilibrium (P < 0.007) was found at D15S165, a polymorphic simple sequence marker physically located within 1 megabase of both CHRNA7 and a partially duplicated, expressed sequence that includes exons 5-10 of CHRNA7. Replication of this result was found in an additional set of families. The results support this region as a chromosomal location involved in the genetic transmission of schizophrenia
— id: 69137, year: 2001, vol: 105, page: 20, stat: Journal Article,

Evidence for the multigenic inheritance of schizophrenia
Freedman, R; Leonard, S; Olincy, A; Kaufmann, C A; Malaspina, D; Cloninger, C R; Svrakic, D; Faraone, S V; Tsuang, M T
2001 Dec 8;105(8):794-800, American journal of medical genetics
Schizophrenia is assumed to have complex inheritance because of its high prevalence and sporadic familial transmission. Findings of linkage on different chromosomes in various studies corroborate this assumption. It is not known whether these findings represent heterogeneous inheritance, in which various ethnic groups inherit illness through different major gene effects, or multigenic inheritance, in which affected individuals inherit several common genetic abnormalities. This study therefore examined inheritance of schizophrenia at different genetic loci in a nationally collected European American and African American sample. Seventy-seven families were previously genotyped at 458 markers for the NIMH Schizophrenia Genetics Initiative. Initial genetic analysis tested a dominant model, with schizophrenia and schizoaffective disorder, depressed type, as the affected phenotype. The families showed one genome-wide significant linkage (Z = 3.97) at chromosome 15q14, which maps within 1 cM of a previous linkage at the alpha 7-nicotinic receptor gene. Chromosome 10p13 showed suggestive linkage (Z = 2.40). Six others (6q21, 9q32, 13q32, 15q24, 17p12, 20q13) were positive, with few differences between the two ethnic groups. The probability of each family transmitting schizophrenia through two genes is greater than expected from the combination of the independent segregation of each gene. Two trait-locus linkage analysis supports a model in which genetic alleles associated with schizophrenia are relatively common in the general population and affected individuals inherit risk for illness through at least two different loci
— id: 69134, year: 2001, vol: 105, page: 794, stat: Journal Article,

Advancing paternal age and the risk of schizophrenia
Malaspina D; Harlap S; Fennig S; Heiman D; Nahon D; Feldman D; Susser ES
2001 Apr;58(4):361-367, Archives of general psychiatry
BACKGROUND: A major source of new mutations in humans is the male germ line, with mutation rates monotonically increasing as father's age at conception advances, possibly because of accumulating replication errors in spermatogonial cell lines. METHOD: We investigated whether the risk of schizophrenia was associated with advancing paternal age in a population-based birth cohort of 87 907 individuals born in Jerusalem from 1964 to 1976 by linking their records to the Israel Psychiatric Registry. RESULTS: Of 1337 offspring admitted to psychiatric units before 1998, 658 were diagnosed as having schizophrenia and related nonaffective psychoses. After controlling for maternal age and other confounding factors (sex, ethnicity, education [to reflect socioeconomic status], and duration of marriage) in proportional hazards regression, we found that paternal age was a strong and significant predictor of the schizophrenia diagnoses, but not of other psychiatric disorders. Compared with offspring of fathers younger than 25 years, the relative risk of schizophrenia increased monotonically in each 5-year age group, reaching 2.02 (95% confidence interval, 1.17-3.51) and 2.96 (95% confidence interval, 1.60-5.47) in offspring of men aged 45 to 49 and 50 years or more, respectively. Categories of mother's age showed no significant effects, after adjusting for paternal age. CONCLUSIONS: These findings support the hypothesis that schizophrenia may be associated, in part, with de novo mutations arising in paternal germ cells. If confirmed, they would entail a need for novel approaches to the identification of genes involved in schizophrenia
— id: 19736, year: 2001, vol: 58, page: 361, stat: Journal Article,

Paternal factors and schizophrenia risk: de novo mutations and imprinting
Malaspina, D
2001 ;27(3):379-393, Schizophrenia bulletin
There is a strong genetic component for schizophrenia risk, but it is unclear how the illness is maintained in the population given the significantly reduced fertility of those with the disorder. One possibility is that new mutations occur in schizophrenia vulnerability genes. If so, then those with schizophrenia may have older fathers, because advancing paternal age is the major source of new mutations in humans. This review describes several neurodevelopmental disorders that have been associated with de novo mutations in the paternal germ line and reviews data linking increased schizophrenia risk with older fathers. Several genetic mechanisms that could explain this association are proposed, including paternal germ line mutations, trinucleotide repeat expansions, and alterations in genetic imprinting in one or several genes involved in neurodevelopment. Animal models may be useful in exploring these and other explanations for the paternal age effect and they may provide a novel approach for gene identification. Finally, it is proposed that environmental exposures of the father, as well as those of the mother and developing fetus, may be relevant to the etiology of schizophrenia
— id: 69135, year: 2001, vol: 27, page: 379, stat: Journal Article,

Traumatic brain injury and schizophrenia in members of schizophrenia and bipolar disorder pedigrees
Malaspina, D; Goetz, R R; Friedman, J H; Kaufmann, C A; Faraone, S V; Tsuang, M; Cloninger, C R; Nurnberger, J I Jr; Blehar, M C
2001 Mar;158(3):440-446, American journal of psychiatry
OBJECTIVE: Schizophrenia following a traumatic brain injury could be a phenocopy of genetic schizophrenia or the consequence of a gene-environment interaction. Alternatively, traumatic brain injury and schizophrenia could be spuriously associated if those who are predisposed to develop schizophrenia have greater amounts of trauma for other reasons. The authors investigated the relationship between traumatic brain injury and psychiatric diagnoses in a large group of subjects from families with at least two biologically related first-degree relatives with schizophrenia, schizoaffective disorder, or bipolar disorder. METHOD: The Diagnostic Interview for Genetic Studies was used to determine history of traumatic brain injury and diagnosis for 1,275 members of multiplex bipolar disorder pedigrees and 565 members of multiplex schizophrenia pedigrees. RESULTS: Rates of traumatic brain injury were significantly higher for those with a diagnosis of schizophrenia, bipolar disorder, and depression than for those with no mental illness. However, multivariate analysis of within-pedigree data showed that mental illness was related to traumatic brain injury only in the schizophrenia pedigrees. Independent of diagnoses, family members of those with schizophrenia were more likely to have had traumatic brain injury than were members of the bipolar disorder pedigrees. The members of the schizophrenia pedigrees also failed to show the gender difference for traumatic brain injury (more common in men than in women) that was expected and was present in the bipolar disorder pedigrees. Subjects with a schizophrenia diagnosis who were members of the bipolar disorder pedigrees (and thus had less genetic vulnerability to schizophrenia) were less likely to have had traumatic brain injury (4.5%) than were subjects with schizophrenia who were members of the schizophrenia pedigrees (and who had greater genetic vulnerability to schizophrenia) (19.6%). CONCLUSIONS: Members of the schizophrenia pedigrees, even those without a schizophrenia diagnosis, had greater exposure to traumatic brain injury compared to members of the bipolar disorder pedigrees. Within the schizophrenia pedigrees, traumatic brain injury was associated with a greater risk of schizophrenia, consistent with synergistic effects between genetic vulnerability for schizophrenia and traumatic brain injury. Posttraumatic-brain-injury schizophrenia in multiplex schizophrenia pedigrees does not appear to be a phenocopy of the genetic disorder
— id: 69140, year: 2001, vol: 158, page: 440, stat: Journal Article,

Data supporting new mutations in the etiology of sporadic schizophrenia
Malaspina, D; Harlap, S; Berman, A; Fahim, C; Friedman, JH; Corcoran, CM; Goetz, R; Brown, A; Goetz, D; Susser, E; Gorman, J
2001 APR 15 ;49(8):85S-85S, Biological psychiatry
— id: 55103, year: 2001, vol: 49, page: 85S, stat: Journal Article,

Positive symptomatology and source-monitoring failure in schizophrenia--an analysis of symptom-specific effects
Brebion, G; Amador, X; David, A; Malaspina, D; Sharif, Z; Gorman, J M
2000 Aug 21;95(2):119-131, Psychiatry research
Recent research has suggested that certain positive symptoms in patients with schizophrenia are linked to self monitoring/reality-monitoring deficits. We wished to investigate the association between such deficits and three specific symptoms: hallucinations, delusions and thought disorganisation. Forty patients with schizophrenia and 40 normal controls were administered a source-monitoring task. Twenty-four items were produced, either verbally by the experimenter, or verbally by the subject, or presented as pictures. Then, subjects were read a recognition list including the produced target items mixed with distractors. They were required to recognise the target items and to remember their source of production. The pattern of memory deficits has previously been reported (Brebion, G., Smith, M., Gorman, J., Amador, X., 1997. Discrimination accuracy and decision biases in different types of reality monitoring in schizophrenia. Journal of Nervous and Mental Disease 185, 247-253). The current analyses focussed on the false recognition of distractors, and on the errors in the source attribution of the recognised target items. Results showed that higher hallucination scores were associated with an increased tendency towards false recognition of non-produced items. In addition, hallucinators were more prone than control subjects to misattribute to another source the items they had produced themselves. Furthermore, hallucinators and delusional patients were more prone than the other patients to report that spoken items had been presented as pictures. This latter finding suggests that both hallucinations and delusions are associated with confusion between imagined and perceived pictures. Our previous report stated that only one of the three investigated types of response bias was associated with global positive symptomatology. However, this finer-grained analysis revealed that the three of them were in fact associated with hallucinations and/or delusions. On the other hand, thought disorganisation appeared to be independent from these mechanisms
— id: 69143, year: 2000, vol: 95, page: 119, stat: Journal Article,

Depression, psychomotor retardation, negative symptoms, and memory in schizophrenia
Brebion, G; Amador, X; Smith, M; Malaspina, D; Sharif, Z; Gorman, J M
2000 Jul;13(3):177-183, Neuropsychiatry neuropsychology & behavioral neurology
OBJECTIVE: The purpose of this study was to examine the relations between depression, psychomotor retardation, and negative symptoms in schizophrenia as well as the specific contribution of each of these factors to memory impairment. BACKGROUND: It has been suggested that depression overlaps with negative symptomatology in schizophrenia. The relation between psychomotor retardation and negative symptomatology has been unclear. METHOD: The Hamilton Depression Rating Scale, The Positive and Negative Symptom Scale for Schizophrenia, and Scale for the Assessment of Negative Symptoms were used to assess depressive and negative symptomatology in a sample of patients with schizophrenia. Verbal memory performance was assessed by a free recall test. Two indices of processing speed were measured. Correlations among variables were computed. RESULTS: Depression score was correlated with the avolition item from the Scale for the Assessment of Negative Symptoms and with both measures of processing speed. Negative symptomatology was unrelated to processing speed. Memory performance was correlated with depression score, slowing of processing speed, and avolition. Its correlation with depression score and processing speed remained significant when the other factors were partialled out. CONCLUSIONS: Memory performance in schizophrenia may be affected by lack of motivation, psychomotor retardation, and depression. It is suggested that negative symptoms could be split between a volitional component linked to depression and cognitive efficiency and an emotional component unrelated to them
— id: 69144, year: 2000, vol: 13, page: 177, stat: Journal Article,

Memory and schizophrenia: differential link of processing speed and selective attention with two levels of encoding
Brebion, G; Smith, M J; Gorman, J M; Malaspina, D; Sharif, Z; Amador, X
2000 Mar-Apr;34(2):121-127, Journal of psychiatric research
The purpose of this study was to investigate how underlying cognitive deficits such as a defect in processing speed or in selective attention contributed to different types of memory impairment observed in schizophrenia (superficial vs deep encoding). 49 schizophrenic patients and 40 normal controls were administered a verbal memory task. Superficial encoding was assessed by the ability to recall items in their serial order. Deep encoding was assessed by the ability to organise words into semantic categories. Two measures of processing speed (Digit Symbol Substitution Test and Stroop colour time) and one measure of selective attention (Stroop test) were used. Regression analyses were carried out. In the patient group, processing speed contributed to both superficial and deep encoding, and to a global verbal memory score. Selective attention only contributed to the superficial encoding processes. Thus, slowing of processing speed in schizophrenia seems to be more crucial for memory performance, since it affects memory in a pervasive way
— id: 69149, year: 2000, vol: 34, page: 121, stat: Journal Article,

Hippocampal pathology in schizophrenia: magnetic resonance imaging and spectroscopy studies
Kegeles, L S; Shungu, D C; Anjilvel, S; Chan, S; Ellis, S P; Xanthopoulos, E; Malaspina, D; Gorman, J M; Mann, J J; Laruelle, M; Kaufmann, C A
2000 May 15;98(3):163-175, Psychiatry research
The hippocampus is a site of previously reported structural and functional abnormalities in schizophrenia. We used magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (MRS) to measure gray matter volumes, the neuronal marker N-acetylaspartate (NAA), and the combination of glutamate (Glu), glutamine (Gln), and gamma-aminobutyric acid (GABA), designated Glx. Measurements were obtained of the medial temporal lobe, centered on the hippocampus, in 10 male patients with schizophrenia (3 neuroleptic-medicated and 7 medication-free), and 10 matched normal volunteers. MRI volumetric measurements and MRS data obtained with short echo time (TE=20 ms) one-dimensional STEAM chemical shift imaging (CSI) on a GE 1.5 Tesla Signa system were analyzed. A laterality index inverted question mark(L-R)/(L+R) was generated from the ratio of Glx to choline-containing compounds (Cho) to test asymmetry changes. Reliability of the MRS measures was assessed with five test-retest studies of healthy volunteers and showed coefficients of variation (CV) in the range of 36-44% for the MRS ratios and standard deviations (S.D.) of 0.15-0.17 for the laterality indices. The Glx/Cho laterality index showed a relative right-sided excess in this region in the patients (-0.23+/-0.20) compared to the controls (+0.06+/-0.20), which was not confounded by tissue composition or placement variability of the MRS voxels. Hippocampal volume deficit and asymmetry were not significant, and other MRS measures showed no differences between patients and controls. The preliminary finding of a lateralized abnormality in Glx is consistent with postmortem findings of asymmetric neurochemical temporal lobe abnormalities in schizophrenia
— id: 69147, year: 2000, vol: 98, page: 163, stat: Journal Article,

Schizophrenia subgroups differing in dichotic listening laterality also differ in neurometabolism and symptomatology
Malaspina, D; Bruder, G; Furman, V; Gorman, J M; Berman, A; Van Heertum, R
2000 Fall;12(4):485-492, Journal of neuropsychiatry & clinical neurosciences
Schizophrenia patients vary in right ear advantage (REA) on dichotic listening tests for assessing left hemispheric dominance for language processing. The authors examined if patients with low REA differed from other patients in symptoms and in resting brain metabolism. SPECT was conducted during visual fixation for 9 healthy control subjects and 16 schizophrenia patients: 8 with normal and 8 with diminished REA. REA-diminished patients had greater positive symptoms and lower mental status scores (all P<0.05) and had right middle temporal gyrus hypermetabolism. Both schizophrenia groups had decreased right frontal and increased medial temporal lobe metabolism vs. control subjects. REA-diminished patients had right temporal lobe hypermetabolism under a resting condition (eyes open, visual fixation). Results suggest reduced right ear (left hemisphere) advantage for dichotic word perception in schizophrenia is related to a predisposition to overactivate right temporal lobe regions and to positive symptoms. In contrast, the prefrontal-medial temporal imbalance present in both patient groups may typify the schizophrenia syndrome
— id: 69142, year: 2000, vol: 12, page: 485, stat: Journal Article,

Relation of familial schizophrenia to negative symptoms but not to the deficit syndrome
Malaspina, D; Goetz, R R; Yale, S; Berman, A; Friedman, J H; Tremeau, F; Printz, D; Amador, X; Johnson, J; Brown, A; Gorman, J M
2000 Jun;157(6):994-1003, American journal of psychiatry
OBJECTIVE: Although a family history of schizophrenia has been associated with negative symptoms, family history is inconsistently related to the presence of the deficit syndrome.METHOD: The authors assessed family history and the deficit syndrome in 99 patients with DSM-III-R-diagnosed schizophrenia who were assessed during clinical treatment. Of these 99 patients, 45 were assessed both while antipsychotic free and during antipsychotic treatment to index their treatment response.RESULTS: Patients with (N=39) and without (N=60) a family history of schizophrenia had similar proportions of the deficit syndrome. Yet family history and deficit syndrome categorizations identified a group with greater negative symptoms on the Positive and Negative Syndrome Scale. Those with a family history had greater emotional withdrawal, poor rapport, and lack of spontaneity. Groups with and without the deficit syndrome similarly differed in these symptoms but also in affective blunting, motor retardation, and passive or apathetic social withdrawal. The study involving antipsychotic-free and antipsychotic treatment phases showed main medication effects explaining positive, psychopathology, depression, and activation symptoms but not negative symptoms. Only patients without a family history had improved negative symptoms with antipsychotic treatment.CONCLUSIONS: Patients with a family history of schizophrenia had greater and more treatment-resistant negative symptoms than those without a family history. They were not more likely to have the deficit syndrome. The group with a family history had more pathology only in negative symptoms related to psychosocial function. The stable negative symptoms specifically related to the genetic vulnerability to inherit schizophrenia might be those associated with psychosocial functioning
— id: 69146, year: 2000, vol: 157, page: 994, stat: Journal Article,

[Left atrium rupture after non-penetrating injury to the back]
Malaspina, D; Guenzati, G; Lemma, M; Botta, M
2000 Nov;1(11):1476-1479, Italian heart journal. Supplement
Survival after cardiac rupture associated with blunt thoracic trauma is very uncommon. In these patients successful management demands a high index of suspicion of cardiac injury. A case of a 24-year-old woman who presented unconscious and shocked in the emergency room after motorcycle trauma strictly limited to her back is reported. Rib and sternal fractures were absent; the typical signs of cardiac tamponade were not found. Therefore the suspicion of cardiac chamber rupture was not immediate and the cardiologist was consulted after several diagnostic exams. Transthoracic echocardiography showed a pericardial effusion with clots and initial cardiac tamponade. The patient was transferred to the operating room and a large hemopericardium was disclosed. Two lacerations were noticed: the first pericardial, near the inferior vena cava, and the second one in the posterior wall of the left atrium. It is possible that the associated pericardial tear and pericardial clots could have contributed to survival. After surgical repair, carried out during cardiopulmonary bypass, the recovery was quick and complete. This case report confirms the possibility of heart chamber rupture after blunt chest trauma even in the absence of obvious thoracic lesion and it shows that the presentation could be very insidious without a 'classic' clinical picture of cardiac tamponade. In front of an unexplained shock after nonpenetrating thoracic trauma, a rupture of the heart chambers should be suspected and echocardiography is mandatory. In the emergency room environment pericardiocentesis should be performed only with a quickly available cardiac surgery or in the presence of overwhelming hemodynamic failure
— id: 69141, year: 2000, vol: 1, page: 1476, stat: Journal Article,

Logical processing, affect, and delusional thought in schizophrenia
Mujica-Parodi, L R; Malaspina, D; Sackeim, H A
2000 Jul-Aug;8(2):73-83, Harvard review of psychiatry
Deficits of logical reasoning have long been considered a hallmark of schizophrenia and delusional disorders. We provide a more precise characterization of 'logic' and, by extension, of 'deficits in logical reasoning.' A model is offered to categorize different forms of logical deficits. This model acknowledges not only problems with making inferences, which is how logic deficits are usually conceived, but also problems in the acquisition and evaluation of premises (i.e., filtering of 'input'). Early (1940-1969) and modern (1970-present) literature on logical reasoning and schizophrenia is evaluated within the context of the presented model. We argue that, despite a substantial history of interest in the topic, research to date has been inconclusive on the fundamental question of whether patients with delusional ideation show abnormalities in logical reasoning. This may be due to heterogeneous definitions of 'logic,' variability in the composition of patient samples, and floor effects among the healthy controls. In spite of these difficulties, the available evidence suggests that deficits in logical reasoning are more likely to occur due to faulty assessment of premises than to a defect in the structure of inferences. Such deficits seem to be provoked (in healthy individuals) or exacerbated (in patients with schizophrenia) by emotional content. The hypothesis is offered that delusional ideation is primarily affect-driven, and that a mechanism present in healthy individuals when they are emotionally challenged may be inappropriately activated in patients who are delusional
— id: 69145, year: 2000, vol: 8, page: 73, stat: Journal Article,

Premorbid speech and language impairments in childhood-onset schizophrenia: association with risk factors
Nicolson, R; Lenane, M; Singaracharlu, S; Malaspina, D; Giedd, J N; Hamburger, S D; Gochman, P; Bedwell, J; Thaker, G K; Fernandez, T; Wudarsky, M; Hommer, D W; Rapoport, J L
2000 May;157(5):794-800, American journal of psychiatry
OBJECTIVE: As both premorbid neurodevelopmental impairments and familial risk factors for schizophrenia are prominent in childhood-onset cases (with onset of psychosis by age 12), their relationship was examined. METHOD: Premorbid language, motor, and social impairments were assessed in a cohort of 49 patients with childhood-onset schizophrenia. Familial loading for schizophrenia spectrum disorders, familial eye-tracking dysfunction, and obstetrical complications were assessed without knowledge of premorbid abnormalities and were compared in the patients with and without developmental impairments. RESULTS: Over one-half of the patients in this group had developmental dysfunction in each domain assessed. The patients with premorbid speech and language impairments had higher familial loading scores for schizophrenia spectrum disorders and more obstetrical complications, and their relatives had worse smooth-pursuit eye movements. The boys had more premorbid motor abnormalities, but early language and social impairments did not differ significantly between genders. There were no other significant relationships between premorbid social or motor abnormalities and the risk factors assessed here. CONCLUSIONS: Premorbid developmental impairments are common in childhood-onset schizophrenia. The rates of three risk factors for schizophrenia (familial loading for schizophrenia spectrum disorders, familial eye-tracking dysfunction, and obstetrical complications) were increased for the probands with premorbid speech and language impairments, suggesting that the pathophysiology of schizophrenia involves the abnormal development of language-related brain regions
— id: 69148, year: 2000, vol: 157, page: 794, stat: Journal Article,

Opposite links of positive and negative symptomatology with memory errors in schizophrenia
Brebion, G; Amador, X; Smith, M J; Malaspina, D; Sharif, Z; Gorman, J M
1999 Oct 18;88(1):15-24, Psychiatry research
We wished to confirm and extend a previous correlational study of our group, suggesting that positive symptoms in schizophrenia were linked to an increase in certain types of memory errors, and negative symptoms to a decrease in other types of errors. A post-hoc analysis was conducted in 33 schizophrenic patients and 40 normal control subjects on memory errors collected in a free recall task and two types of recognition tasks. The memory errors were intrusions and list errors in free recall, and decision bias towards false alarms in recognition, all assumed to reflect a source-monitoring failure. In a first analysis, the patient sample was split along the median for positive symptoms as rated by the Scale for the Assessment of Positive Symptoms (SAPS). In a second analysis, it was split along the median for negative symptoms as rated by the Scale for the Assessment of Negative Symptoms (SANS). Patients with high ratings of positive symptoms made more memory errors (intrusions, list errors, false alarms) than those with low ratings, supporting the hypothesis of a link between positive symptomatology and source-monitoring failure. On the other hand, patients with high ratings of negative symptoms made fewer of these errors than the other patients. Fewer errors were specifically associated with more affective flattening, alogia and anhedonia, whereas avolition was entirely unrelated to them
— id: 69150, year: 1999, vol: 88, page: 15, stat: Journal Article,

Suggestive linkage of chromosome 10p to schizophrenia is not due to transmission ratio distortion
Faraone, S V; Meyer, J; Matise, T; Svrakic, D; Pepple, J; Malaspina, D; Suarez, B; Hampe, C; Chan, G; Aelony, A; Friedman, J H; Kaufmann, C; Cloninger, C R; Tsuang, M T
1999 Dec 15;88(6):607-608, American journal of medical genetics
The genome scan of the European-American schizophrenia families from the Human Genetics Initiative of the National Institute of Mental Health (NIMH) reported a suggestive linkage to chromosome 10p. Subsequently, Paterson and Petronis [1999] reported evidence for transmission ratio distortion on 10p to females. They suggested that transmission ratio distortion to females might have created spurious evidence for linkage to 10p. To address this issue, we reanalyzed our 10p data using only male-male affected sibling pairs. The two chromosome 10p markers that gave the most evidence for linkage in our prior report continued to show evidence for linkage: D10S1423 (NPL Z = 3.0, P = 0.001) and its neighbor D10S582 (NPL Z = 2.9, P = 0.002). These data suggest that our prior report of suggestive linkage of schizophrenia to markers on 10p cannot be attributed to the transmission ratio distortion to females reported by Paterson and Petronis. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:607-608, 1999
— id: 69152, year: 1999, vol: 88, page: 607, stat: Journal Article,

Suicidal behavior in schizophrenia: characteristics of individuals who had and had not attempted suicide
Harkavy-Friedman, J M; Restifo, K; Malaspina, D; Kaufmann, C A; Amador, X F; Yale, S A; Gorman, J M
1999 Aug;156(8):1276-1278, American journal of psychiatry
OBJECTIVE: This study compares demographic and clinical characteristics of 52 individuals with schizophrenia or schizoaffective disorder who had attempted suicide with those of 104 individuals with schizophrenia or schizoaffective disorder who had not made a suicide attempt. METHOD: Participants were interviewed with the Diagnostic Interview for Genetic Studies. RESULTS: Most suicide attempts were of moderate to severe lethality, required medical attention, and involved significant suicidal intent. Individuals who had and had not attempted suicide did not differ with respect to demographic variables, duration of illness, rate of depression, or substance abuse. The two groups are affected differentially when depressed. CONCLUSIONS: Biopsychosocial assessments and interventions are essential for reducing the risk for suicidal behavior in individuals with schizophrenia
— id: 69156, year: 1999, vol: 156, page: 1276, stat: Journal Article,

Brain event-related potentials (ERPs) in schizophrenia during a word recognition memory task
Kayser, J; Bruder, G E; Friedman, D; Tenke, C E; Amador, X F; Clark, S C; Malaspina, D; Gorman, J M
1999 Dec;34(3):249-265, International journal of psychophysiology
Impairments of recognition memory for words and attenuation of the ERP 'old-new' effect have been found in patients with left medial temporal lobe damage. If left temporal lobe dysfunction in schizophrenia involves medial structures (e.g. hippocampus), then schizophrenic patients might show similar abnormalities of verbal recognition memory. This study recorded ERPs from 30 electrode sites while subjects were engaged in a continuous word recognition memory task. Results are reported for 24 patients having a diagnosis of schizophrenia (n = 16) or schizoaffective disorder (n = 8) and 19 age-matched healthy controls. Both patients and controls showed the expected 'old-new' effect, with greater late positivity to correctly recognized old words at posterior sites, and there was also no significant difference between groups in P3 amplitude. However, accuracy of word recognition memory was poorer in patients than controls, and patients showed markedly smaller N2 amplitude. Reduced amplitudes of N2 and N2-P3 were associated with poorer performance, with highest correlations over the left inferior parietal (N2) and left medial parietal (N2-P3) region. Moreover, patients failed to show significantly greater left than right hemisphere amplitude of N2-P3 at posterior sites, which was seen for healthy controls. These findings suggest that impaired word recognition in schizophrenia may arise from a left lateralized deficit at an early stage of processing, beginning at 200-300 ms after word onset
— id: 69151, year: 1999, vol: 34, page: 249, stat: Journal Article,

Amphetamine disrupts P50 suppression in normal subjects
Light, G A; Malaspina, D; Geyer, M A; Luber, B M; Coleman, E A; Sackeim, H A; Braff, D L
1999 Oct 1;46(7):990-996, Biological psychiatry
BACKGROUND: P50 suppression is viewed as an operational measure of sensory 'gating' that is reduced in patients with schizophrenia and their family members. Previous reports have demonstrated that neural gating is regulated by monoaminergic tone in rodent models of P50 suppression. METHODS: In this study, 11 healthy subjects participated in P50 event-related potential recordings at baseline and after either oral administration of dextroamphetamine (.3 mg/kg) or placebo, to determine if the administration of a monoaminergic agonist produces P50 suppression deficits similar to those observed in patients with schizophrenia. RESULTS: As hypothesized, amphetamine disrupted the suppression of the P50 event-related potential. There was a statistically significant decrement in P50 suppression during the amphetamine challenge condition (t10 = 3.15, p < .01, mean difference = -44.1%, d = -2.5) relative to the baseline P50 condition. A comparison of P50 suppression in the placebo and amphetamine conditions (both after a baseline recording session) revealed a significant amphetamine-induced disruption of P50 suppression (t6 = 3.71, p < .01, mean difference = -54.4%, d = -3.14). CONCLUSIONS: The biochemical alterations associated with an amphetamine-induced disruption of P50 suppression in this study may be related to the pathophysiology of P50 suppression deficits in schizophrenia. The findings are consistent with several careful examinations of suppression deficits in rodent models that have identified the monoaminergic regulation of P50 suppression. These data indicate that amphetamine induces a disruption of P50 suppression in normal subjects
— id: 69155, year: 1999, vol: 46, page: 990, stat: Journal Article,

SPECT study of visual fixation in schizophrenia and comparison subjects
Malaspina, D; Storer, S; Furman, V; Esser, P; Printz, D; Berman, A; Lignelli, A; Gorman, J; Van Heertum, R
1999 Jul 1;46(1):89-93, Biological psychiatry
BACKGROUND: The consistent association of impaired eye movements and schizophrenia suggests a relationship between the neurobiology of the illness and visual pursuit systems. Visual fixation (VF), an eye 'movement' task at zero velocity, is the simplest such abnormality in schizophrenia patients and their relatives. METHODS: We used a VF task for a functional imaging study. Six neuroleptic-free schizophrenia patients and eight gender and mean age matched comparison subjects had SPECT scans with 20 mCi of Tc99-HMPAO, during VF on a simple blue line intersection. MEDX data saved in ANALYZE format for SPM 95 was used to generate paired t-test statistical data for display in Talairach space, with rCBF changes given as Z-scores. RESULTS: Patients, compared to controls, had increased rCBF in both the parahippocampal gyrus (bilaterally) and in the right fusiform gyrus. They had decreased rCBF in the left frontal cortex, including medial and superior frontal gyri and anterior cingulate. Overall, compared to controls, patients had medial temporal lobe hyperperfusion along with left prefrontal hypoperfusion. CONCLUSIONS: These findings are consistent with the hypothesized imbalance between the medial temporal and frontal lobes that is postulated for schizophrenia. It was of interest that the relative rCBF differences between schizophrenia patients and controls in this small sample were observable with this cognitively non-demanding visual fixation task
— id: 69158, year: 1999, vol: 46, page: 89, stat: Journal Article,

Interaction of genes and prenatal exposures in schizophrenia
Malaspina, Dolores; Sohler, Nancy L; Susser, Ezra S
Prenatal exposures in schizophrenia Washington, DC, US: American Psychiatric Association, 1999,
(from the chapter) This chapter introduces the developing field of research in schizophrenia. The authors examine the genetic epidemiological research that strongly suggests some sort of multifactorial causation of schizophrenia and some basic models of multifactorial causation, which can include both genetic and environmental factors. Furthermore the authors examine current evidence for gene-environment interaction in schizophrenia and new research designed to investigate interactions between genes and prenatal exposures in schizophrenia.
— id: 4120, year: 1999, vol: , page: 35, stat: Chapter,

Clinical and neurobiological correlates of cytogenetic abnormalities in childhood-onset schizophrenia
Nicolson, R; Giedd, J N; Lenane, M; Hamburger, S; Singaracharlu, S; Bedwell, J; Fernandez, T; Thaker, G K; Malaspina, D; Rapoport, J L
1999 Oct;156(10):1575-1579, American journal of psychiatry
OBJECTIVE: Cytogenetic abnormalities are increased in schizophrenia, suggesting a possible etiologic contribution. However, their clinical and pathophysiologic roles in the disorder are unknown. To investigate this, a group of children and adolescents participating in a comprehensive study of childhood-onset schizophrenia were screened for chromosomal abnormalities, and their clinical and neurobiological correlates were examined. METHOD: Cytogenetic screening with the use of high-resolution banding, fluorescent in situ hybridization for chromosome 22q11 deletions, and molecular fragile X testing was undertaken in a group of 47 children and adolescents with very early onset of schizophrenia. Clinical, neurobiological (including brain morphometry), and risk factor measures of the subjects with cytogenetic abnormalities were compared with those of the remaining patients without cytogenetic anomalies. RESULTS: Five patients had previously undiagnosed cytogenetic abnormalities. Lower performance IQ and more pronounced premorbid developmental impairments were seen in this subgroup. Rates of obstetric complications, familial schizophrenia spectrum disorders, and familial eye tracking dysfunction were similar for the patients with and without cytogenetic abnormalities. CONCLUSIONS: Cytogenetic abnormalities appear to be increased in childhood-onset schizophrenia, suggesting an association with a very early age at onset. The data from the subgroup of patients with cytogenetic anomalies are consistent with a model in which a childhood onset of schizophrenia is due to a greater impairment of neurodevelopment secondary to the interaction of a number of factors, particularly genetic ones
— id: 69154, year: 1999, vol: 156, page: 1575, stat: Journal Article,

Obstetrical complications and childhood-onset schizophrenia
Nicolson, R; Malaspina, D; Giedd, J N; Hamburger, S; Lenane, M; Bedwell, J; Fernandez, T; Berman, A; Susser, E; Rapoport, J L
1999 Oct;156(10):1650-1652, American journal of psychiatry
OBJECTIVE: Increased obstetrical complications have been reported in individuals with adult-onset schizophrenia, with several studies finding an association between such complications and an earlier age at onset. Consequently, obstetrical records were examined for individuals with childhood-onset schizophrenia to determine if birth complications were more prevalent. METHOD: The birth records of 36 patients with childhood-onset schizophrenia and 35 sibling comparison subjects were rated for birth complications by two psychiatrists who were unaware of group membership. RESULTS: There were no significant differences between the groups in rates of obstetrical complications. Patients with such complications did not have a relatively earlier age at onset of schizophrenia. CONCLUSIONS: A very early age at onset of schizophrenia is probably not due to birth complications
— id: 69153, year: 1999, vol: 156, page: 1650, stat: Journal Article,

Elevation of CD5+ B lymphocytes in schizophrenia
Printz, D J; Strauss, D H; Goetz, R; Sadiq, S; Malaspina, D; Krolewski, J; Gorman, J M
1999 Jul 1;46(1):110-118, Biological psychiatry
BACKGROUND: A variety of immunologic alterations have been observed in patients with schizophrenia. These findings have lent support to theories that autoimmune mechanisms may be important in some patients with the illness. The CD5+ B lymphocyte, a B-cell subset associated with autoimmune disease, has been the subject of two previously published studies yielding disparate results. METHODS: In this study, we used immunofluorescent flow cytometry to measure CD5+ B cells, total B and T cells, and CD4 and CD8 subsets in patients with schizophrenia and in normal control subjects. RESULTS: A significantly higher percentage of patients with schizophrenia, relative to normal control subjects, exhibited an elevated level of CD5+ B cells (27.6% vs 6.7%). Antipsychotic withdrawal had no effect on CD5+ B-cell levels, suggesting that medication effects were not the cause of this difference. No other studied lymphocyte subsets differed between the two groups. CONCLUSIONS: A subset of patients with schizophrenia have elevated levels of CD5+ B cells. This finding replicates an earlier study by another group and provides further evidence suggestive of autoimmune manifestations in schizophrenia
— id: 69157, year: 1999, vol: 46, page: 110, stat: Journal Article,

Word recognition, discrimination accuracy, and decision bias in schizophrenia: association with positive symptomatology and depressive symptomatology
Brebion, G; Smith, M J; Amador, X; Malaspina, D; Gorman, J M
1998 Oct;186(10):604-609, Journal of nervous & mental disease
The purpose of this experiment was to replicate and extend to a memory task Bentall and Slade's (1985) finding that hallucinations in schizophrenic patients were linked to a liberal decision bias. A word recognition task was administered to 40 schizophrenic patients and 40 normal controls that yielded two indices of performance: an index of discrimination accuracy (Pr) and one of decision bias (Br). Patients obtained a lower Pr than controls, whereas Br was similar in both groups. In patients, Br was selectively correlated with positive symptomatology: the more the positive symptoms, the more liberal the bias. In particular, there was a specific correlation between decision bias and hallucinations. Conversely, Pr was inversely correlated with severity of depression, but not with either positive or negative symptoms. Thus, positive symptomatology may be linked more to difficulties in distinguishing between representations of internal versus external events than to deficits in encoding external events
— id: 69159, year: 1998, vol: 186, page: 604, stat: Journal Article,

Resistance to interference and positive symptomatology in schizophrenia
Brebion, Gildas; Smith, Mark; Gorman, Jack; Malaspina, Dolores; Amador, Xavier
1998 ;3(3):179-190 Aug, Cognitive neuropsychiatry
Investigated opposing theories of resistance to interference and positive symptomatology in schizophrenia by assessing the interference effect in the Stroop colour and word test, and its correlation with positive symptomatology in 40 schizophrenic inpatients (mean age 34.1 yrs) and 40 normal controls. Two hypotheses were pitted against each other: (1) that a positive correlation would be observed between interference and positive symptoms, suggesting that positive symptoms were linked to a deficit in inhibition of nonrelevant stimuli; and (2) that a negative correlation would be observed, suggesting that positive symptoms were linked to resistance to disruption by nonrelevant stimuli. The amount of interference was not significantly increased in patients. No positive correlation with symptoms was observed, invalidating the first hypothesis. A negative correlation was observed, however, between the amount of interference and the score of hallucinations. This confirmed the second hypothesis (i.e. more hallucinations being associated with more resistance to distractors). It is proposed that resistance to negative priming, to latent inhibition, and to interference in patients with positive symptomatology stem from incomplete processing of distractor information.
— id: 69130, year: 1998, vol: 3, page: 179, stat: Journal Article,

Genome-wide search for schizophrenia susceptibility loci: the NIMH Genetics Initiative and Millennium Consortium
Cloninger, C R; Kaufmann, C A; Faraone, S V; Malaspina, D; Svrakic, D M; Harkavy-Friedman, J; Suarez, B K; Matise, T C; Shore, D; Lee, H; Hampe, C L; Wynne, D; Drain, C; Markel, P D; Zambuto, C T; Schmitt, K; Tsuang, M T
1998 Jul 10;81(4):275-281, American journal of medical genetics
Schizophrenia has a complex pattern of inheritance, indicative of interactions among multiple genes and environmental factors. The detection and replication of specific susceptibility loci for such complex disorders are facilitated by the availability of large samples of affected sib pairs and their nuclear families, along with standardized assessment and systematic ascertainment procedures. The NIMH Genetics Initiative on Schizophrenia, a multisite collaborative study, was established as a national resource with a centralized clinical data base and cell repository. The Millennium Schizophrenia Consortium has completed a genome-wide scan to detect susceptibility loci for schizophrenia in 244 individuals from the nuclear families of 92 independent pairs of schizophrenic sibs ascertained by the NIMH Genetics Initiative. The 459 marker loci used in the scan were spaced at 10-cM intervals on average. Individuals of African descent were higher than those of European descent in their average heterozygosity (79% vs. 76%, P < .0001) and number of alleles per marker (9.2 vs. 8.4, P < .0001). Also, the allele frequencies of 73% of the marker loci differed significantly (P < .01) between individuals of European and African ancestry. However, regardless of ethnic background, this sample was largely comprised of schizophrenics with more than a decade of psychosis associated with pervasive social and occupational impairment
— id: 69163, year: 1998, vol: 81, page: 275, stat: Journal Article,

Genome scan of European-American schizophrenia pedigrees: results of the NIMH Genetics Initiative and Millennium Consortium
Faraone, S V; Matise, T; Svrakic, D; Pepple, J; Malaspina, D; Suarez, B; Hampe, C; Zambuto, C T; Schmitt, K; Meyer, J; Markel, P; Lee, H; Harkavy Friedman, J; Kaufmann, C; Cloninger, C R; Tsuang, M T
1998 Jul 10;81(4):290-295, American journal of medical genetics
The Genetics Initiative of the National Institute of Mental Health (NIMH) was a multisite study that created a national repository of DNA from families informative for genetic linkage studies of schizophrenia, bipolar disorder, and Alzheimer's disease. The schizophrenia families were collected by three sites: Washington University, Harvard University, and Columbia University. This article, one in a series that describes the data collected for linkage analysis by the schizophrenia consortium, presents the results for the European-American sample. The European-American sample comprised 43 nuclear families and 146 subjects. Ninety-six of the family members were considered affected by virtue of having received a DSM-III-R diagnosis of schizophrenia (N = 82) or schizoaffective disorder, depressed (N = 14). The families contained a total of 50 independent sib-pairs. Using the significance threshold criteria suggested by Lander and Kruglyak [(1995): Nat Genet 241-247], no region showed statistically significant evidence for linkage; two markers on chromosome 10p showed statistical evidence suggestive of linkage using the criteria of Lander and Kruglyak [(1995): Nat Genet 241-247]: D10S1423 (nonparametric linkage (NPL) Z = 3.4, P = .0004) and its neighbor, D10S582 (NPL Z = 3.2, P = .0006)
— id: 69161, year: 1998, vol: 81, page: 290, stat: Journal Article,

NIMH Genetics Initiative Millenium Schizophrenia Consortium: linkage analysis of African-American pedigrees
Kaufmann, C A; Suarez, B; Malaspina, D; Pepple, J; Svrakic, D; Markel, P D; Meyer, J; Zambuto, C T; Schmitt, K; Matise, T C; Harkavy Friedman, J M; Hampe, C; Lee, H; Shore, D; Wynne, D; Faraone, S V; Tsuang, M T; Cloninger, C R
1998 Jul 10;81(4):282-289, American journal of medical genetics
The NIMH Genetics Initiative is a multi-site collaborative study designed to create a national resource for genetic studies of complex neuropsychiatric disorders. Schizophrenia pedigrees have been collected at three sites: Washington University, Columbia University, and Harvard University. This article-one in a series that describes the results of a genome-wide scan with 459 short-tandem repeat (STR) markers for susceptibility loci in the NIMH Genetics Initiative schizophrenia sample-presents results for African-American pedigrees. The African-American sample comprises 30 nuclear families and 98 subjects. Seventy-nine of the family members were considered affected by virtue of having received a DSMIII-R diagnosis of schizophrenia (n = 71) or schizoaffective disorder, depressed (n = 8). The families contained a total of 42 independent sib pairs. While no region demonstrated evidence of significant linkage using the criteria suggested by Lander and Kruglyak, several regions, including chromosomes 6q16-6q24, 8pter-8q12, 9q32-9q34, and 15p13-15q12, showed evidence consistent with linkage (P = 0.01-0.05), providing independent support of findings reported in other studies. Moreover, the fact that different genetic loci were identified in this and in the European-American samples, lends credence to the notion that these genetic differences together with differences in environmental exposures may contribute to the reported differences in disease prevalence, severity, comorbidity, and course that has been observed in different racial groups in the United States and elsewhere
— id: 69162, year: 1998, vol: 81, page: 282, stat: Journal Article,

Further investigation of a chromosome 15 locus in schizophrenia: analysis of affected sibpairs from the NIMH Genetics Initiative
Leonard, S; Gault, J; Moore, T; Hopkins, J; Robinson, M; Olincy, A; Adler, L E; Cloninger, C R; Kaufmann, C A; Tsuang, M T; Faraone, S V; Malaspina, D; Svrakic, D M; Freedman, R
1998 Jul 10;81(4):308-312, American journal of medical genetics
Linkage of a neurophysiological deficit associated with schizophrenia, i.e., the failure to inhibit the auditory P50 response, was previously reported at chromosome 15q14. The marker with the highest pairwise lod score, D15S1360, was isolated from a yeast artificial chromosome containing a candidate gene, the alpha7-nicotinic acetylcholine receptor gene. In the present study, this linkage was further investigated in a subset of the NIMH Genetics Initiative schizophrenia families. These families have not been studied neurophysiologically, as were the families in the original report. Therefore, the DSMIII-R diagnosis of schizophrenia was used as the affected phenotype. Twenty families fulfilled the criteria of at least one sibpair concordant for schizophrenia, along with their two parents or another affected relative outside the nuclear family, available for genotyping. Sibpair analysis showed a significant proportion of D15S1360 alleles shared identical-by-descent (0.58; P < 0.0024). The results further support the involvement of this chromosomal locus in the genetic transmission of schizophrenia
— id: 69160, year: 1998, vol: 81, page: 308, stat: Journal Article,

Psychobiological heterogeneity of familial and sporadic schizophrenia
Malaspina, D; Friedman, J H; Kaufmann, C; Bruder, G; Amador, X; Strauss, D; Clark, S; Yale, S; Lukens, E; Thorning, H; Goetz, R; Gorman, J
1998 Apr 1;43(7):489-496, Biological psychiatry
BACKGROUND: Although schizophrenia is presumed to be heterogeneous, there has been limited success distinguishing familial from sporadic cases. We used psychobiological measures to examine heterogeneity, as they may be closer to neurobiology than symptoms. Smooth pursuit eye movement quality (SPEM) and dichotic listening (DL) tests to tones and words were used to assess hemispheric laterality asymmetry. METHODS: Forty-six research unit patients participated in assessments of family history (FH) and physiological measures. FH was categorized by three exclusive groups: FH-1 patients had a chronic schizophrenia-related psychosis in a first-degree relative, FH-2 had it in second-degree relative, and FH-3 had no family member with a reoccurrence. RESULTS: Analysis of variance showed a significant group difference for SPEM and DL tones. SPEM was significantly worse in all three schizophrenia groups than for the normal comparison subjects. Among the schizophrenia groups, the nonfamilial group (FH-3) had the worst SPEM quality, FH-2 had intermediate quality, and FH-1 had the best quality. Conversely, only the nonfamilials (FH-3) had normal right hemispheric lateralization for tones, whereas familials did not, and FH-2 again had intermediate values. The lateralization quotient for DL words did not significantly differ among the groups. CONCLUSIONS: SPEM was affected most in sporadic, not familial schizophrenia, whereas dichotic listening was most affected in familial schizophrenia. This double dissociation supports the utility of the familial/sporadic distinction and suggests that etiological factors in different forms of schizophrenia may impact principally on distinct neurobiological substrates, despite similar patient phenomenology
— id: 69165, year: 1998, vol: 43, page: 489, stat: Journal Article,

SPECT imaging of odor identification in schizophrenia
Malaspina, D; Perera, G M; Lignelli, A; Marshall, R S; Esser, P D; Storer, S; Furman, V; Wray, A D; Coleman, E; Gorman, J M; Van Heertum, R L
1998 Apr 10;82(1):53-61, Psychiatry research
Deficits in olfactory identification, despite normal odor perception, are found in some neuropsychiatric disorders, including schizophrenia. We examined if regional cerebral blood flow (rCBF) differed between schizophrenia patients and controls during odor identification, hypothesizing that these brain regions could be relevant to odor identification impairments. Eight schizophrenia and eight comparison subjects provided a baseline (picture identity matching) and activation (odor identification) SPECT scan, obtained using 99mTc-HMPAO in a low dose/high dose design. Six patients and seven controls had analyzable data. MEDX data saved in ANALYZE format for SPM 95 generated paired t-test statistical data for display in Talairach space, with rCBF changes given as Z-scores. There was no schizophrenia vs. control group difference in rCBF for the baseline picture-matching test. For odor identification, schizophrenia patients had a hypometabolic right-sided cortical region that included the frontal lobe Broca's area, superior temporal lobe, and supramarginal and angular gyri. Post hoc within-group contrasts of picture-matching vs. odor identification showed that the controls significantly increased rCBF in the right-sided inferior temporal fusiform gyrus, and bilateral hippocampi and visual association areas for the odor test. The schizophrenia group showed no rCBF differences for picture-matching compared to odor identification. Patients showed significant hypometabolism in right-sided cortical areas for odor identification. They also failed to show increased rCBF in the hippocampus and visual association area, as seen in controls for odor identification compared to picture-matching. These regions may be unique to schizophrenia or have broader implications for olfactory memory retrieval
— id: 69164, year: 1998, vol: 82, page: 53, stat: Journal Article,

Clinical correlates of memory in schizophrenia: differential links between depression, positive and negative symptoms, and two types of memory impairment
Brebion, G; Smith, M J; Amador, X; Malaspina, D; Gorman, J M
1997 Nov;154(11):1538-1543, American journal of psychiatry
OBJECTIVE: This study investigated clinical correlates of memory impairment in schizophrenic patients. In particular, the authors hypothesized that depressive symptoms would be linked to memory efficiency, as found in other clinical populations. In addition, they tested Frith's pathophysiological model predicting links between negative symptoms and failure to respond, as well as between positive symptoms and production of erroneous responses. METHOD: Thirty-one patients were given several memory tasks: long-term free recall of nonorganizable and organizable lists in immediate and delayed conditions, recognition in immediate and delayed conditions, implicit memory (stem completion task), and short-term memory (digit span). Superficial encoding of information was also assessed by the ability to recall the items sequentially; deep encoding was assessed by the ability to organize the items according to their semantic properties. Two types of memory measures were individualized: measures reflecting memory efficiency and measures reflecting production of erroneous memory responses (intrusions, perseverations, false alarms). RESULTS: Consistent correlations appeared between severity of depressive symptoms and measures reflecting deep but not superficial encoding; none, however, was correlated with negative symptoms. Two of the three types of erroneous memory responses were positively linked to positive symptoms. CONCLUSIONS: Efficiency of memory processes relying on deep encoding seemed linked to depressive symptoms. In addition, the two distinct types of impairment predicted by Frith's model were found. The expected link of one with positive symptoms was verified, but the link of the other with negative symptoms was not
— id: 69167, year: 1997, vol: 154, page: 1538, stat: Journal Article,

Effects of clozapine on plasma catecholamines and relation to treatment response in schizophrenia: a within-subject comparison with haloperidol
Brown, A S; Gewirtz, G; Harkavy-Friedman, J; Cooper, T; Brebion, G; Amador, X F; Malaspina, D; Gorman, J M
1997 Nov;17(5):317-325, Neuropsychopharmacology
We conducted a within-subject comparison of the effects of clozapine and haloperidol on plasma levels of neurotransmitters and metabolites, and related changes in specific plasma neurochemicals with clozapine response. The subjects were 14 inpatients with schizophrenia or schzoaffective disorder, who were refractory to haloperidol and at least one other typical antipsychotic medication. Subjects underwent, in the following order: a 6-week 'fixed, flexible dose' haloperidol trial, followed by a 2-4 week medication-free phase, and a 6-week clozapine trial. Plasma levels of norepinephrine (NE), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG), and objective clinical ratings of total, positive, negative, and depressive symptoms were obtained at the end of each phase. As expected, we found a substantial increase of plasma NE with clozapine but not with haloperidol. However, the increase in NE was not associated with improvement in total or positive symptomatology. There was some evidence for an association between improvement in negative symptoms and increased HVA on clozapine, as well as diminished HVA during the medication-free phase. The implications of these data for understanding the mechanisms of action of clozapine are discussed
— id: 69166, year: 1997, vol: 17, page: 317, stat: Journal Article,

Anticipation in schizophrenia: biology or bias?
Johnson, J E; Cleary, J; Ahsan, H; Harkavy Friedman, J; Malaspina, D; Cloninger, C R; Faraone, S V; Tsuang, M T; Kaufmann, C A
1997 May 31;74(3):275-280, American journal of medical genetics
Anticipation is a genetic phenomenon wherein age of disease onset decreases and/ or severity increases in successive generations. Anticipation has been demonstrated for several neuropsychiatric disorders with expanding trinucleotide repeats recently identified as the underlying molecular mechanism. We report here the results of an analysis of anticipation performed with multiplex families segregating schizophrenia. Thirty-three families were identified through the NIMH Genetics Initiative that met the following criteria: had at least two affected members in successive generations and were not bilineal. Affectation diagnoses included schizophrenia, schizoaffective disorder-depressed, and psychosis NOS. Additional analyses included the Cluster A personality disorders. Three indices of age of onset were used. Disease severity was measured by several different indices. Four sampling schemes as suggested by McInnis et al. were tested, as well as additional analysis using pairs ascertained through the parental generation. Anticipation was demonstrated for age of onset, regardless of the index or sampling scheme used (P<0.05). Anticipation was not supported for disease severity. Analyses that took into account drug use and diminished fecundity did not affect the results. While the data strongly support intergenerational differences in disease onset consistent with anticipation, they must be viewed cautiously given unavoidable biases attending these analyses
— id: 69168, year: 1997, vol: 74, page: 275, stat: Journal Article,

Diminished cardiac vagal tone in schizophrenia: associations to brain laterality and age of onset
Malaspina, D; Bruder, G; Dalack, G W; Storer, S; Van Kammen, M; Amador, X; Glassman, A; Gorman, J
1997 Mar 1;41(5):612-617, Biological psychiatry
We measured high-frequency (rapid) heart rate variability (HRV) from 24-hour Holter electrocardiograms to index cardiovagal tone in 23 patients with DSM-III-R schizophrenia or schizoaffective disorder. High-frequency HRV, quantitated by measuring the percent of successive normal interbeat intervals greater than 50 msec (PNN50), demonstrated a bimodal distribution: 11 of 23 patients had a PNN50 of > and = 8.0 (mean value = 17.7 +/- 11.0), and 12 had a PNN50 of < and = 4.0 (mean value = 1.8 +/- 1.0); no subject had a PNN50 value between 4.0 and 8.0. All 12 low cardiovagal tone patients (versus only 6/11 of the other patients) had a schizophrenia (not schizoaffective) diagnosis (p = .013). PNN50 was not associated with present age, gender, smoking, IQ scores, or symptomatology, but patients with lower cardiovagal tone did have a significantly later age of onset (20.5 +/- 5.3 vs. 14.8 +/- 2.8 years: p = .005). PNN50 subgroups also differed on dichotic listening measures of brain laterality. The low group failed to show left ear (right hemisphere) advantage for complex tones seen in the other patients and normal adults. They also showed larger right ear (left hemisphere) advantage for dichotic words than the other patients. This evidence of relative right hemisphere disadvantage in patients with low cardiovagal tone is consistent with findings linking autonomic nervous system and right hemisphere function. These findings also support the existence of subgroups of schizophrenia patients differing in autonomic activity, brain laterality, and clinical features
— id: 69170, year: 1997, vol: 41, page: 612, stat: Journal Article,

Psychosis and etiology
Tremeau, F; Amador, X; Malaspina, D
1997 Jan;154(1):132-134, American journal of psychiatry
— id: 69171, year: 1997, vol: 154, page: 132, stat: Journal Article,

Spiking fevers with clozapine treatment
Tremeau, F; Clark, S C; Printz, D; Kegeles, L S; Malaspina, D
1997 Apr;20(2):168-170, Clinical neuropharmacology
Clozapine often causes low-grade fever and less frequently spiking fever. We describe three cases of spiking fever that occurred in the first 3 weeks of clozapine therapy. A new set of side effects of clozapine is identified, which includes spiking fever, respiratory and gastrointestinal symptoms, and neutrophilia. Possible mechanisms are discussed
— id: 69169, year: 1997, vol: 20, page: 168, stat: Journal Article,

Diagnostic accuracy and confusability analyses: an application to the Diagnostic Interview for Genetic Studies
Faraone, S V; Blehar, M; Pepple, J; Moldin, S O; Norton, J; Nurnberger, J I; Malaspina, D; Kaufmann, C A; Reich, T; Cloninger, C R; DePaulo, J R; Berg, K; Gershon, E S; Kirch, D G; Tsuang, M T
1996 Mar;26(2):401-410, Psychological medicine
The dominant, contemporary paradigm for developing and refining diagnoses relies heavily on assessing reliability with kappa coefficients and virtually ignores a core component of psychometric practice: the theory of latent structures. This article describes a psychometric approach to psychiatric nosology that emphasizes the diagnostic accuracy and confusability of diagnostic categories. We apply these methods to the Diagnostic Interview for Genetic Studies (DIGS), a structured psychiatric interview designed by the NIMH Genetics Initiative for genetic studies of schizophrenia and bipolar disorder. Our results show that sensitivity and specificity were excellent for both DSM-III-R and RDC diagnoses of major depression, bipolar disorder, and schizophrenia. In contrast, diagnostic accuracy was substantially lower for subtypes of schizoaffective disorder-especially for the DSM-III-R definitions. Both the bipolar and depressed subtypes of DSM-III-R schizoaffective disorder had excellent specificity but poor sensitivity. The RDC definitions also had excellent specificity but were more sensitive than the DSM-III-R schizoaffective diagnoses. The source of low sensitivity for schizoaffective subtypes differed for the two diagnostic systems. For RDC criteria, the schizoaffective subtypes were frequently confused with one another; they were less frequently confused with other diagnoses. In contrast, the DSM-III-R subtypes were often confused with schizophrenia, but not with each other
— id: 69172, year: 1996, vol: 26, page: 401, stat: Journal Article,

Visual fixation and smooth pursuit eye movement abnormalities in patients with schizophrenia and their relatives
Amador, X F; Malaspina, D; Sackeim, H A; Coleman, E A; Kaufmann, C A; Hasan, A; Gorman, J M
1995 Spring;7(2):197-206, Journal of neuropsychiatry & clinical neurosciences
Increasing evidence suggests that smooth pursuit eye movement (SPEM) dysfunction may serve as an endophenotype or genetic marker of schizophrenia. The authors tested SPEM and visual fixation (VF) in 31 patients with schizophrenia, 33 of their first-degree relatives, and 24 patients with major depressive disorder. A high rate of abnormal VF was found in schizophrenic patients and their first-degree relatives, but not in affective disorder patients with or without psychotic features. Rate of VF abnormality distinguished schizophrenic patients from acutely depressed mood disorder patients; SPEM did not. VF and SPEM performance correlated only moderately, suggesting that the pathophysiologies of these two eye movement abnormalities may be partially independent. Implications for identifying a schizophrenia endophenotype are discussed
— id: 69174, year: 1995, vol: 7, page: 197, stat: Journal Article,

Smaller right ear (left hemisphere) advantage for dichotic fused words in patients with schizophrenia
Bruder, G; Rabinowicz, E; Towey, J; Brown, A; Kaufmann, C A; Amador, X; Malaspina, D; Gorman, J M
1995 Jun;152(6):932-935, American journal of psychiatry
OBJECTIVE: The purposes of this study were to compare right ear (left hemisphere) advantage for dichotic words in schizophrenia and depression and to assess its association with antipsychotic medication, symptom ratings, and gender. METHOD: Thirty-two schizophrenic patients and 65 patients with major depression were given the Fused Rhymed Words Test, a dichotic listening measure of hemispheric dominance for language. RESULTS: An earlier finding of smaller left hemisphere advantage in schizophrenic patients was replicated. There was no significant change in ear advantage in a subgroup of the schizophrenic patients tested when they were taking neuroleptics and when they were not. The smaller left hemisphere advantage in the schizophrenic patients was not dependent on gender but was related to symptom ratings on the Positive and Negative Syndrome Scale. CONCLUSIONS: The findings are consistent with a left hemisphere dysfunction in schizophrenia, which is associated with positive symptoms
— id: 69173, year: 1995, vol: 152, page: 932, stat: Journal Article,

Effects of pharmacologic catecholamine manipulation on smooth pursuit eye movements in normals
Malaspina, D; Colemann, E A; Quitkin, M; Amador, X F; Kaufmann, C A; Gorman, J M; Sackeim, H A
1994 Sep;13(2):151-159, Schizophrenia research
The pathophysiology of schizophrenia may be related directly or indirectly to abnormal dopaminergic activity. Both subcortical excess and frontal cortical deficiency of dopamine have been suggested, and primary or downstream failures of dopamine activation to the prefrontal cortex has been posited to explain some of the cognitive deficiencies in schizophrenia patients. Although the prefrontal cortex may also be a site for the disruption of smooth pursuit eye movements (SPEM), the most substantially described psychophysiological marker for schizophrenia vulnerability, no relationship of SPEM to dopaminergic activity has been demonstrated. In this study we explored the effect of altered dopamine function on SPEM quality through pharmacological manipulation of catecholamine tone in 11 healthy subjects. The subjects had SPEM measured at baseline, and under challenge conditions including amphetamine (0.3 mg/kg), haloperidol (2 mg), placebo, and combined amphetamine with haloperidol. Changes in the profile of mood scale (POMS) confirmed the expected subjective central nervous system effects the agents. Placebo and amphetamine had no effect on qualitative ratings of SPEM, but haloperidol, alone and in combination with amphetamine, disrupted eye tracking, producing a pattern of small saccadic intrusions characteristic of patients with schizophrenia. These findings link dopaminergic blockade with SPEM disruption in normal subjects
— id: 69176, year: 1994, vol: 13, page: 151, stat: Journal Article,

Odor discrimination deficits in schizophrenia: association with eye movement dysfunction
Malaspina, D; Wray, A D; Friedman, J H; Amador, X; Yale, S; Hasan, A; Gorman, J M; Kaufmann, C A
1994 Summer;6(3):273-278, Journal of neuropsychiatry & clinical neurosciences
Odor discrimination deficits were found in 80% of 20 schizophrenia patients and in none of the 20 age- and sex-matched comparison subjects. Olfactory discrimination was reliably measured in the patients. Twelve patients in this study also had smooth pursuit eye movement (SPEM) qualitatively recorded. The olfactory discrimination scores were highly correlated to SPEM but not to other clinical measures. This correlation suggests a shared neurobiology, possibly involving working memory
— id: 69177, year: 1994, vol: 6, page: 273, stat: Journal Article,

Smooth pursuit eye movement abnormality in severe major depression: Effects of ECT and clinical recovery
Malaspina, Dolores; Amador, Xavier F; Coleman, Eliza A; Mayr, Tiffany L; et al
1994 ;6(1):36-42, Journal of neuropsychiatry & clinical neurosciences
Evaluated the effects of clinical state on smooth pursuit eye movement (SPEM) quality in 24 inpatients with depression. The comparison groups consisted of 30 patients with chronic schizophrenia and 20 normal Ss. Prior to ECT, SPEM abnormality characterized 42% of the depressed Ss, 60% of the schizophrenic Ss, and 5% of the normal Ss. SPEM was significantly correlated to Hamilton Rating Scale for Depression scores in the depressed Ss. Although SPEM was transiently disrupted by an acute ECT treatment, it improved during the treatment course. This improvement of SPEM quality with clinical recovery suggests that SPEM abnormality may be a state marker in severe major depression, in contrast to its invariable trait nature in schizophrenia.
— id: 69132, year: 1994, vol: 6, page: 36, stat: Journal Article,

The significance of clinical EEG abnormalities in depressed patients treated with ECT
Malaspina, Dolores; Devanand, D. P; Krueger, Richard B; Prudic, Joan; et al
1994 ;10(4):259-266 Dec, Convulsive therapy
Examined the relationships between routinely obtained clinical electroencephalogram (EEG) evaluations, clinical features, and treatment response in 140 Ss with Research Diagnostic Criteria endogenous major depression. Ss were randomly assigned to low- and high-dosage forms of unilateral and bilateral ECT conditions. Ss with abnormal EEG findings tended to show a poorer rate of response to unilateral ECT, but a strong rate of response to bilateral ECT. Rates and timing of relapse were equivalent in the 2 groups. Little evidence was found that EEG abnormalities characterize discrete subgroups or have productive utility with respect to ECT outcome.
— id: 69131, year: 1994, vol: 10, page: 259, stat: Journal Article,

Epidemiology and genetics of neuropsychiatric disorders
Malaspina, Dolores; Quitkin, H. Matthew; Kaufmann, Charles A
Synopsis of neuropsychiatry Washington, DC, US: American Psychiatric Association, 1994,
(from the chapter) [explores how] clinicians have suspected roles for both exogenous and endogenous factors in the etiology of disease / [examine how] the powerful techniques of epidemiology and genetics have enabled us to identify specific environmental and hereditary contributions to [psychiatric] illness
— id: 4121, year: 1994, vol: , page: 157, stat: Chapter,

Diagnostic interview for genetic studies. Rationale, unique features, and training. NIMH Genetics Initiative
Nurnberger, J I Jr; Blehar, M C; Kaufmann, C A; York-Cooler, C; Simpson, S G; Harkavy-Friedman, J; Severe, J B; Malaspina, D; Reich, T
1994 Nov;51(11):849-859, Archives of general psychiatry
This article reports on the development and reliability of the Diagnostic Interview for Genetic Studies (DIGS), a clinical interview especially constructed for the assessment of major mood and psychotic disorders and their spectrum conditions. The DIGS, which was developed and piloted as a collaborative effort of investigators from sites in the National Institute of Mental Health (NIMH) Genetics Initiative, has the following additional features: (1) polydiagnostic capacity; (2) a detailed assessment of the course of the illness, chronology of psychotic and mood syndromes, and comorbidity; (3) additional phenomenologic assessments of symptoms; and (4) algorithmic scoring capability. The DIGS is designed to be employed by interviewers who exercise significant clinical judgment and who summarize information in narrative form as well as in ratings. A two-phase test-retest (within-site, between-site) reliability study was carried out for DSM-III-R criteria-based major depression, bipolar disorder, schizophrenia, and schizoaffective disorder. Reliabilities using algorithms were excellent (0.73 to 0.95), except for schizoaffective disorder, for which disagreement on estimates of duration of mood syndromes relative to psychosis reduced reliability. A final best-estimate process using medical records and information from relatives as well as algorithmic diagnoses is expected to be more reliable in making these distinctions. The DIGS should be useful as part of archival data gathering for genetic studies of major affective disorders, schizophrenia, and related conditions
— id: 69175, year: 1994, vol: 51, page: 849, stat: Journal Article,

Molecular genetics of schizophrenia
Kaufmann, Charles A; Malaspina, Dolores
1993 ;23(3):111-122 Mar, Psychiatric annals
Asserts that while the contribution of heritable factors in schizophrenia (SCZ) has long been suspected, recent advances in population and molecular genetics promise to reveal the chromosomal location, and ultimately, the identity of these factors. As a complex disorder, SCZ poses certain challenges, including an unknown mode of inheritance, diagnostic stability, and etiologic heterogeneity. Specific strategies have been developed to address these complexities, and molecular genetic studies of SCZ have begun in earnest. To date, the only positive finding is an unconfirmed linkage between Chromosome 5q and SCZ.
— id: 69133, year: 1993, vol: 23, page: 111, stat: Journal Article,

Association of schizophrenia and partial trisomy of chromosome 5p. A case report
Malaspina, D; Warburton, D; Amador, X; Harris, M; Kaufmann, C A
1992 Jul;7(2):191-196, Schizophrenia research
A normal balanced chromosome 5 translocation carrier (5:14) (p14.1; q32.3) produced one offspring with a 5p deletion syndrome (cri du chat syndrome) and two with a partial trisomy (one with schizophrenia and the other with refractory epilepsy). We had hypothesized that the translocation might be complex and involve 5q, overlapping with a schizophrenia associated area described by Bassett et al., (1988). Cytogenetic study, however, indicated that there was no overlap in the involved chromosome 5 trisomy for this individual with schizophrenia and the trisomic region previously described. The probands with the trisomy and the cytogenetic findings are described in this report. Alternative interpretations are suggested to explain the association of schizophrenia and chromosomal abnormalities
— id: 69178, year: 1992, vol: 7, page: 191, stat: Journal Article,

Epidemiology and genetics of neuropsychiatric disorders
Malaspina, Dolores; Quitkin, H. Matthew; Kaufmann, Charles A
American Psychiatric Press textbook of neuropsychiatry (2nd ed.) Washington, DC, US: American Psychiatric Association, 1992,
(from the chapter) focus on the application of these disciplines [epidemiology and genetics] to the study of neuropsychiatric disorders [in order to identify specific environmental and hereditary contributions to illness] /// basal ganglia disease / degenerative illnesses of childhood / dementia / epilepsy / muscle disorders
— id: 4122, year: 1992, vol: , page: 187, stat: Chapter,

Occult thyroid dysfunction in patients with refractory depression
Gewirtz, G R; Malaspina, D; Hatterer, J A; Feureisen, S; Klein, D; Gorman, J M
1988 Aug;145(8):1012-1014, American journal of psychiatry
Assessment of metabolic rate was useful in evaluating refractory depression in six of 15 women. Five of the six had normal levels of T3 and T4; however, each had an elevated thyrotropin-stimulating hormone level or a low metabolic rate. The depressions responded to medication with thyroid hormone
— id: 69179, year: 1988, vol: 145, page: 1012, stat: Journal Article,

Hepatitis in 101 consecutive suburban cocaine and opiate users
Estroff, T W; Extein, I L; Malaspina, D; Gold, M S
1986 1987;16(3):237-242, International journal of psychiatry in medicine
The records of 101 cocaine and/or heroin drug abusing patients admitted consecutively to Fair Oaks Hospital were evaluated for history of IV drug abuse, antigen and serum antibody evidence of hepatitis A and B infection, and elevation of serum SGPT. One patient, an IV user, had hepatitis B antigen present in his blood. No patient had acute hepatitis A (IgM) antibody present. Forty-five out of fifty-three (84.9%) IV abusers were Hep B Ab positive, while two out of twenty-nine non-IV abusers (6.9%) were positive. Twenty of fifty-three (43.4%) IV users had positive hepatitis A Ab while one of twenty-nine (3.4%) of non-IV users were positive. Thirty-five of fifty-five (63.6%) IV users had elevated SGPT compared to five of forty-one (12.2%) in non-IV users. IV users tended to be older than non-IV users. The data presented in this article indicate that there is a greatly increased incidence of both hepatitis A and B in IV drug users compared to non-IV users and that the hepatitis B incidence is increased in a far greater amount than could be expected in a normal population. The type of drug injected (heroin, other opiates, or cocaine) was not an important determinant. The presence of hepatitis B antibodies in any drug abusing patient who denies IV use is a strong indication that they may not be telling the truth about their past drug abuse. It makes little difference whether drug abusing patients live in the inner city or the suburbs.(ABSTRACT TRUNCATED AT 250 WORDS)
— id: 69180, year: 1986, vol: 16, page: 237, stat: Journal Article,