Karen A Nolan, Ph.D.

STOP SIGNAL TASK PERFORMANCE AND SUBCORTICAL VOLUMES IN PATIENTS WITH SCHIZOPHRENIA OR SCHIZOAFFECTIVE DISORDER
Hoptman, Matthew J.; Nolan, K. A.; D'Angelo, D.; Mauro, C. J.; Nair-Collins, S.; Javitt, Daniel C.
2011 MAR ;37(6022):211-212, Schizophrenia bulletin
— id: 128822, year: 2011, vol: 37, page: 211, stat: Journal Article,

Effect of the neuroprotective peptide davunetide (AL-108) on cognition and functional capacity in schizophrenia
Javitt DC; Buchanan RW; Keefe RS; Kern R; McMahon RP; Green MF; Lieberman J; Goff DC; Csernansky JG; McEvoy JP; Jarskog F; Seidman LJ; Gold JM; Kimhy D; Nolan KS; Barch DS; Ball MP; Robinson J; Marder SR
2011 Dec 12;:?-? #, Schizophrenia research
BACKGROUND: Cognitive dysfunction is a key predictor of functional disability in schizophrenia. Davunetide (AL-108, NAP) is an intranasally administered peptide currently being developed for treatment of Alzheimer's disease and related disorders. This study investigates effects of davunetide on cognition in schizophrenia. METHOD: Sixty-three subjects with schizophrenia received davunetide at one of two different doses (5, 30mg) or placebo for 12weeks in a multicenter, double-blind, parallel-group randomized clinical trial. The MATRICS Consensus Cognitive Battery (MCCB) assessed cognitive effects. The UCSD Performance-based Skills Assessment (UPSA) and the Schizophrenia Cognition Rating Scale (SCoRS) assessed functional capacity. Subjects continued their current antipsychotic treatment during the trial. RESULTS: There were no significant differences in MCCB change between davunetide and placebo over the three treatment arms (p=.45). Estimated effect-size (d) values were .34 and .21 favoring the 5 and 30mg doses vs. placebo, respectively. For UPSA, there was a significant main effect of treatment across study arms (p=.048). Between-group effect size (d) values were.74 and .48, favoring the 5 and 30mg doses, respectively. No significant effects were observed on the SCoRS or on symptom ratings. No significant side effects or adverse events were observed. CONCLUSION: Davunetide was well tolerated. Effects of davunetide on MCCB-rated cognition were not significant relative to placebo. In contrast, a significant beneficial effect was detected for the UPSA. Based upon effect-size considerations, sample sizes of at least 45-50 subjects/group would be required to obtain significant effects on both MCCB and UPSA, providing guidance for continued clinical development in schizophrenia
— id: 150124, year: 2011, vol: , page: ?, stat: Journal Article,

Self-report and laboratory measures of impulsivity in patients with schizophrenia or schizoaffective disorder and healthy controls
Nolan, Karen A; D'Angelo, Debra; Hoptman, Matthew J
2011 May 15;187(1-2):301-303, Psychiatry research
This study examined self-reported impulsivity and aggression and performance on the stop-signal task in patients with schizophrenia or schizoaffective disorder and healthy volunteers. Compared to controls, patients had higher scores on interview and questionnaire measures of impulsivity and aggression and showed increased stop-signal reaction time and greater response variability. These findings are consistent with a specific impairment in response inhibition in schizophrenia
— id: 130292, year: 2011, vol: 187, page: 301, stat: Journal Article,

Rare NRXN1 promoter variants in patients with schizophrenia
Shah, Abhishek K; Tioleco, Nina M; Nolan, Karen; Locker, Joseph; Groh, Katherine; Villa, Catalina; Stopkova, Pavla; Pedrosa, Erika; Lachman, Herbert M
2010 May 14;475(2):80-84, Neuroscience letters
Copy number variants (CNVs) affecting the neurexin 1 (NRXN1) gene have been found in a subgroup of patients with schizophrenia (SZ). NRXN1 expression is complex, with multiple alternative splice forms generated from two major transcripts; NRXN1alpha and NRXN1beta. The majority of CNVs in SZ are deletions affecting the proximal NRXN1alpha exons and promoter region. Rare chromosomal events are useful in understanding the genetic basis of complex psychiatric disorders since affected genes become feasible targets to analyze for more subtle genetic alterations. As a first step towards this goal, we resequenced the NRXN1alpha promoter region in 170 patients with SZ and a similar number of controls. Two rare mutations were identified in the patient population. One previously unknown single nucleotide polymorphism (SNP) was found in controls. Bioinformatics analysis suggests that binding to several transcription factors may be affected by the minor alleles. The findings suggest that in addition to chromosomal alterations disrupting the NRXN1alpha promoter, rare point mutations in the region may also be involved in SZ pathogenesis
— id: 133439, year: 2010, vol: 475, page: 80, 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,

Adolescent cannabis use, psychosis and catechol-O-methyltransferase genotype in African Americans and Caucasians
Kantrowitz, Joshua T; Nolan, Karen A; Sen, Srijan; Simen, Arthur A; Lachman, Herbert M; Bowers, Malcolm B Jr
2009 Dec;80(4):213-218, Psychiatric quarterly
Cannabis has been reported as a likely risk factor for the development of psychosis, and a gene x environment interaction with the catechol-O-methyltransferase (COMT) gene has been proposed. Moreover, COMT has been separately linked to affective symptoms in psychosis. Despite a high rate of cannabis abuse and affective symptoms in African Americans, no studies exploring a relationship between COMT and psychosis in this group have been reported. An existing database of psychotic patients with and without adolescent cannabis use/affective symptoms was examined, and chi-square analyses for independence were applied separately for both Caucasians and African-Americans to examine genotype associations with adolescent cannabis use and affective symptoms (past or present). The two subject groups did not differ with respect to the prevalence of adolescent cannabis abuse or presence of affective symptoms. Further study is needed, with non-psychotic controls and larger samples
— id: 138375, year: 2009, vol: 80, page: 213, stat: Journal Article,

Staff and Patient Views of the Reasons for Aggressive Incidents: A Prospective, Incident-Based Study
Nolan, Karen A; Shope, Constance B; Citrome, Leslie; Volavka, Jan
2009 Sep;80(3):167-172, Psychiatric quarterly
Aggression is a serious problem in psychiatric hospitals. It is not clear whether reasons for aggression guide which therapeutic interventions are selected. Aggression was monitored in participants in a randomized clinical trial of the antiaggressive efficacy of adjunctive valproate in patients with schizophrenia. The Overt Aggression Scale was used to record aggression type and severity, reasons given by patients and staff, and interventions delivered. Forty two patients caused 317 aggressive incidents. Patients reported more often than staff that aggression was provoked by external factors (e.g., interpersonal conflict, limit-setting). Staff cited internal factors (e.g., psychotic symptoms, tension) more often than patients. Interventions administered were related to type and severity of aggression but not to either staff or patients' reasons. Responses to aggressive events do not take causes into account. It is possible that consideration of the reasons for the aggressive behavior might yield more targeted interventions
— id: 99436, year: 2009, vol: 80, page: 167, stat: Journal Article,

Analysis of a promoter polymorphism in the SMDF neuregulin 1 isoform in Schizophrenia
Pedrosa, Erika; Nolan, Karen A; Stefanescu, Radu; Herskovits, Pnina; Novak, Tomas; Zukov, Ilja; Stopkova, Pavla; Lachman, Herbert M
2009 ;59(4):205-212, Neuropsychobiology
BACKGROUND/AIMS: Neuregulin 1 (NRG1) is a positional candidate gene in schizophrenia (SZ). Two major susceptibility loci in the NRG1 gene approximately one million nucleotides apart have been identified in genetic studies. Several candidate functional allelic variants have been described that might be involved in disease susceptibility. However, the findings are still preliminary. We recently mapped active promoters and other regulatory domains in several SZ and bipolar disorder (BD) candidate genes using ChIP-chip (chromatin immunoprecipitation hybridized to microarrays). One was the promoter for the NRG1 isoform, SMDF, which maps to the 3' end of the gene complex. Analysis of the SNP database revealed several polymorphisms within the approximate borders of the region immunoprecipitated in our ChIP-chip experiments, one of which is rs7825588. METHODS: This SNP was analyzed in patients with SZ and BD and its effect on promoter function was assessed by electromobility gel shift assays and luciferase reporter constructs. RESULTS: A significant increase in homozygosity for the minor allele was found in patients with SZ (genotype distribution chi(2) = 7.32, p = 0.03) but not in BD (genotype distribution chi(2) = 0.52, p = 0.77). Molecular studies demonstrated modest, but statistically significant allele-specific differences in protein binding and promoter function. CONCLUSION: The findings suggest that homozygosity for rs725588 could be a risk genotype for SZ
— id: 133713, year: 2009, vol: 59, page: 205, stat: Journal Article,

Public-academic partnerships: integrating state psychiatric hospital treatment and clinical research
Citrome, Leslie; Epstein, Henry; Nolan, Karen A; Tremeau, Fabien; Elin, Charles; Roy, Biman; Levine, Jerome
2008 Sep;59(9):958-960, Psychiatric services
Collaboration between state clinical treatment services and academic research is fertile ground for clinical research opportunities. Such joint initiatives require careful planning, including provisions for joint training, integration of research staff into clinical activities, and integration of clinical treatment staff into research activities. The authors describe the planning and development of a 24-bed research unit at the Nathan S. Kline Institute for Psychiatric Research, colocated on the same campus as Rockland Psychiatric Center, each of which is an independent facility operated by the New York State Office of Mental Health
— id: 81566, year: 2008, vol: 59, page: 958, stat: Journal Article,

Resting functional connectivity correlates of stop signal task performance
D'Angelo, D; Nolan, KA; Margulies, DS; Mauro, CJ; Milham, MP; Hoptman, MJ
2008 APR 1 ;63(7):6S-6S, Biological psychiatry
— id: 78662, year: 2008, vol: 63, page: 6S, stat: Journal Article,

Atypical antipsychotics, neurocognitive deficits, and aggression in schizophrenic patients
Krakowski, Menahem I; Czobor, Pal; Nolan, Karen A
2008 Oct;28(5):485-493, Journal of clinical psychopharmacology
The purpose of this study was to compare the effects of olanzapine, clozapine, and haloperidol on neurocognitive function in schizophrenic patients who present with documented episodes of physical aggression and to determine whether change in cognitive function is related to aggression. One hundred physically aggressive schizophrenic inpatients were assigned to a randomized, double-blind, parallel-group, 12-week treatment, and received cognitive evaluations at baseline. There were 33, 34, and 33 subjects in the clozapine, olanzapine, and haloperidol groups, respectively. They were administered a battery of tests assessing psychomotor function, general executive function, visual and verbal memory, and visuospatial ability. A general cognitive index was derived from the above battery. The overall score on the Modified Overt Aggression Scale was used to measure the number and severity of the aggressive events. Psychiatric symptoms and side effects were also assessed. The improvement in the general cognitive index differed significantly among the 3 treatment groups, with olanzapine being superior to both haloperidol and clozapine. Further analyses revealed significantly greater improvement with olanzapine in several cognitive domains. Furthermore, improvement in the general cognitive index was significantly associated with a decrease in aggression in the olanzapine group but not in the other 2 medication groups. In violent schizophrenic patients, olanzapine treatment is associated with better cognitive functioning relative to haloperidol and clozapine. This improvement in neurocognitive function is associated with a decrease in aggressive behavior. As clozapine markedly reduced aggression, there may be different pathways for the antiaggressive effect of olanzapine and that of clozapine
— id: 95757, year: 2008, vol: 28, page: 485, stat: Journal Article,

Reducing Inpatient Aggression: Does Paying Attention Pay Off?
Nolan, Karen A; Citrome, Leslie
2008 Jun;79(2):91-95, Psychiatric quarterly
OBJECTIVE: Inpatient aggression is poorly documented in official records. Video technology can improve detection, but is labor-intensive and costly. We examined the effectiveness of interventions to improve reporting on a secure inpatient research unit equipped with audio/video surveillance. METHOD: Systematic review of all video recorded during a six-week period in 2000 revealed that official documentation omitted 16/71 aggressive incidents (23%). Subsequent interventions to improve reporting involved therapy aides, whose jobs entail continuous direct contact with patients. We reviewed the corresponding period in 2005 to investigate changes in aggression and reporting. RESULTS: Although the number of aggressive incidents did not change significantly, reporting improved: 59/62 (95%) events detected in 2005 had been reported. Physical aggression decreased and verbal aggression increased. CONCLUSIONS: Improved reporting may have the unanticipated benefit of reducing physical aggression, perhaps by fostering recognition of and intervention in events that might otherwise escalate into more serious aggression
— id: 74592, year: 2008, vol: 79, page: 91, stat: Journal Article,

Methodological structure for aggression research
Volavka, Jan; Nolan, Karen A
2008 Dec;79(4):293-300, Psychiatric quarterly
Kendler's seminal essay listed 8 major propositions outlining a philosophical framework for the entire field of psychiatry [Kendler (American Journal of Psychiatry 162:433-440, 2005)]. These propositions have grounded psychiatric research on a coherent conceptual basis. The field of aggression research needs a general conceptual framework that would help us to integrate the contributions of neurobiology, sociology, criminology, and other areas. All of Kendler's propositions are generally relevant in this respect. The aim of the current article is to develop specific applications of four of Kendler's propositions for aggression research. These four propositions are: 'Psychiatry is irrevocably grounded in mental, first-person experiences', 'Psychiatric disorders are etiologically complex, and we can expect no more 'spirochete-like' discoveries that will explain their origin in simple terms', 'Explanatory pluralism is preferable to monistic explanatory approaches, especially biological reductionism', and 'Acceptance of Patchy Reductionism'
— id: 94040, year: 2008, vol: 79, page: 293, stat: Journal Article,

Risperidone alone versus risperidone plus valproate in the treatment of patients with schizophrenia and hostility
Citrome, Leslie; Shope, Constance B; Nolan, Karen A; Czobor, Pal; Volavka, Jan
2007 Nov;22(6):356-362, International clinical psychopharmacology
The objective of the study was to compare the antiaggressive efficacy of risperidone monotherapy versus risperidone plus valproate in patients with schizophrenia. This was an 8-week open-label randomized parallel group clinical trial in hospitalized adults diagnosed with schizophrenia and with hostile behavior. Patients were randomly assigned to receive risperidone alone (n=16) or risperidone plus valproate (n=17). To minimize bias, raters were blinded to the assigned treatment arm. Outcome measures included the Positive and Negative Syndrome Scale (PANSS), Buss-Durkee Hostility Inventory (BDHI), Barratt Impulsiveness Scale (BIS), Nurses Observation Scale for Inpatient Evaluation (NOSIE), and the Overt Aggression Scale (OAS). Although significantly fewer patients randomized to monotherapy completed the study (chi=8.62, d.f.=1, P=0.003), no significant differences between monotherapy or combination treatment were observed in change of the BDHI, BIS, NOSIE, PANSS total scores, OAS measures of aggressive behavior or the hostility item of the PANSS. In conclusion, although patients receiving combination treatment were more likely to complete the study, we were unable to detect a meaningful advantage for combination therapy as measured by rating scales
— id: 74400, year: 2007, vol: 22, page: 356, stat: Journal Article,

Cognitive and behavioral correlates of COMT genotype in schizophrenia
Nolan K; Lachman H; Bilder R
2007 ;:61-61 #110, WCBG ... Abstract Book (World Congress on Psychiatric Genetics)
— id: 76062, year: 2007, vol: , page: 61, stat: Journal Article,

Positive association of schizophrenia to JARID2 gene
Pedrosa, E; Ye, K; Nolan, KA; Morrell, L; Okun, JM; Persky, AD; Saito, T; Lachman, HM
2007 JAN 5 ;144B(1):45-51, American journal of medical genetics. Part B, Neuropsychiatric genetics
Dysbindin (DTNBP1) is a positional candidate gene for 6p22.3-linked schizophrenia (SZ). However, so far, no disease-causing alleles have been identified. DTNBP1 is immediately adjacent to JARID2, a member of the ARID (AT-rich interaction domain) family of transcription modulators. We have previously suggested that proteins which bind to AT-rich domains could play a role in SZ pathogenesis. Consequently, we explored the possibility that JARID2 itself could be a candidate gene for 6p22.3-linked SZ. We used a case control design to analyze single nucleotide polymorphisms (SNPs) and insertion/deletion variants affecting AT-rich domains in both the DTNBP1 and JARID2 genes. Three of the DTNBP1 SNPs analyzed had previously been shown to be associated with SZ. We did not detect any significant difference in allele, genotype or haplotype distribution for any of these DTNBP1 markers. However, we did detect a significant difference in allele distribution for a tetranucleotide repeat polymorphism in the JARID2 gene that affects an AT-rich domain. A significant increase in short alleles (less than 11 repeats) was found in patients with SZ (x(2) =7.02; P=0.008). No other JARID2 marker displayed statistically significant allele and genotype distributions. Our findings suggest that JARID2 should be viewed as a candidate gene for 6p22.3-linked SZ. (c) 2006 Wiley-Liss, Inc
— id: 70140, year: 2007, vol: 144B, page: 45, stat: Journal Article,

Analysis of polymorphisms in AT-rich domains of neuregulin 1 gene in schizophrenia
Lachman, Herbert M; Pedrosa, Erika; Nolan, Karen A; Glass, Max; Ye, Kenny; Saito, Takuya
2006 Jan 5;141(1):102-109, American journal of medical genetics. Part B, Neuropsychiatric genetics
Linkage analysis and association studies have pointed to neuregulin 1 (NRG1) as the prime candidate for 8p-linked schizophrenia (SZ). However, so far, no specific functional alleles in the gene's exons, intron-exon junctions and promoters have been identified that are unequivocally associated with SZ. In this study, we analyzed several NRG1 polymorphisms that affect ATTT motifs and AT-rich regions of the gene. We have previously identified a number of such polymorphisms in the promoters of other SZ and bipolar disorder (BD) candidate genes and found positive associations to several of them. In addition, allele specific differences in the binding of brain proteins have been found for many of the polymorphisms. A case control design was used to compare allele frequencies in Caucasian and African American patients with SZ and controls. In the African American group, a significant difference was found in the allele and genotype distribution for several of the markers and haplotype blocks located in the 5'- and 3'-ends of the gene. The most significant result was obtained for rs6150532, an insertion/deletion variant in a conserved region of an intron that separates two small, alternatively spliced exons. Allele-specific and developmental differences were detected in the binding of a brain protein using newborn rat pups when probes containing the two rs6150532 alleles were used in electromobility gel shift assays. There were no significant differences in allele or genotype distribution found for any of the markers in the Caucasian sample. Although the samples size is relatively small, the findings support a role for NRG1 in SZ in African Americans and suggest that polymorphic differences in regions of the gene that recognize AT-binding proteins may be a factor in disease pathogenesis. (c) 2005 Wiley-Liss, Inc
— id: 62400, year: 2006, vol: 141, page: 102, stat: Journal Article,

Antisocial behavior and schizophrenia: Clues to etiology?
Nolan, KA; Hoptman, M; Volavka', J
2006 JAN ;81(3):256-257, Schizophrenia research
— id: 63294, year: 2006, vol: 81, page: 256, stat: Journal Article,

Video recording in the assessment of violent incidents in psychiatric hospitals
Nolan, Karea A; Volavka, Jan
2006 Jan;12(1):58-63, Journal of psychiatric practice
Research into causes and management of aggressive behavior in mental illness has been hampered by difficulties related to the accurate detection, description, and classification of aggression. Much aggressive behavior, particularly verbal aggression, is unreported or reported inaccurately. We describe the use of video surveillance to study aggression in psychiatric inpatients. The videos supplement or correct eyewitness accounts, accurately identifying aggressors and victims, as well as specific aggressive behaviors. Video has provided a tool for studying behavioral precursors and environmental catalysts of assaults. These observations have contributed to our efforts to create a typology of aggression based on underlying causes. Furthermore, video has played a direct role in clinical care, documenting or revealing medication side effects, as well as feigned or self-induced injuries. The ethical and responsible use of video surveillance of psychiatric inpatients has the potential to enhance our understanding and treatment of aggression
— id: 66472, year: 2006, vol: 12, page: 58, stat: Journal Article,

Catechol-O-methyltransferase and monoamine oxidase-A polymorphisms and treatment response to typical and atypical neuroleptics
Nolan, Karen A; Czobor, Pal; Citrome, Leslie L; Krakowski, Menachem; Lachman, Herbert M; Kennedy, James L; Ni, Xingqun; Lieberman, Jeffrey; Chakos, Miranda; Volavka, Jan
2006 Jun;26(3):338-340, Journal of clinical psychopharmacology
— id: 64739, year: 2006, vol: 26, page: 338, stat: Journal Article,

The relationship between history of violent and criminal behavior and recognition of facial expression of emotions in men with schizophrenia and schizoaffective disorder
Weiss EM; Kohler CG; Nolan KA; Czobor P; Volavka J; Platt MM; Brensinger C; Loughead J; Delazer M; Gur RE; Gur RC
2006 ;32(3):187-194, Aggressive Behavior
Social psychological research underscores the relation between aggression and emotion. Specifically, regulating negative affect requires the ability to appraise restraint-producing cues, such as facial signs of anger, fear and other emotions. Individuals diagnosed with major mental disorders are more likely to have engaged in violent behavior than mentally healthy members of the same communities. We examined whether violent and criminal behavior in men with schizophrenia is related to emotion recognition abilities. Forty-one men with schizophrenia underwent a computerized emotion discrimination test presenting mild and extreme intensities of happy, sad, angry, fearful and neutral faces, balanced for gender and ethnicity. History of violence was assessed by the Life History of Aggression Scale and official records of arrests. Psychopathology was rated using the Positive and Negative Symptom Scale. Criminal behavior was associated with poor emotion recognition, especially for fearful and angry facial expressions. History of aggression was also associated with more severe positive symptoms and less severe negative symptoms. These findings suggest that misinterpretation of social cues such as angry and fearful expression may lead to a failure in socialization and adaptive behavior in response to emotional situation, which may result in a higher number of criminal arrests
— id: 66473, year: 2006, vol: 32, page: 187, stat: Journal Article,

Aggression and psychopathology in treatment-resistant inpatients with schizophrenia and schizoaffective disorder
Nolan, Karen A; Volavka, Jan; Czobor, Pal; Sheitman, Brian; Lindenmayer, Jean-Pierre; Citrome, Leslie L; McEvoy, Joseph; Lieberman, Jeffrey A
2005 Jan;39(1):109-115, Journal of psychiatric research
Positive psychotic symptoms, such as threat/'control-override' delusions or command hallucinations, have been related to aggression in patients with schizophrenia. However, retrospective data collection has hampered evaluation of the direct influence of psychopathology on aggressive behavior. In this study, we monitored aggressive behavior and psychopathology prospectively and in close temporal proximity in 157 treatment-resistant inpatients diagnosed with chronic schizophrenia or schizoaffective disorder participating in a 14-week double-blind clinical trial. Aggressive behavior was rated with the overt aggression scale (OAS). Psychopathology was assessed using the positive and negative syndrome scale (PANSS). At baseline, subjects who would be aggressive during the study had higher scores on only two PANSS items: hostility and poor impulse control. During the study PANSS positive subscale scores were significantly higher in aggressive subjects. Total PANSS scores were higher within 3 days of an aggressive incident, as were positive and general psychopathology subscale scores. However, in a smaller subsample for whom PANSS ratings were available within 3 days before aggressive incidents, only scores on the PANSS positive subscale were significantly higher. These findings in chronic, treatment resistant inpatients support the view that positive symptoms may lead to aggression
— id: 51093, year: 2005, vol: 39, page: 109, stat: Journal Article,

Efficacy of clozapine, olanzapine, risperidone, and haloperidol in schizophrenia and schizoaffective disorder assessed with nurses observation scale for inpatient evaluation
Volavka, Jan; Nolan, Karen A; Kline, Linda; Czobor, Pal; Citrome, Leslie; Sheitman, Brian; Lindenmayer, Jean-Pierre; McEvoy, Joseph; Lieberman, Jeffrey A
2005 Jul 1;76(1):127-129, Schizophrenia research
— id: 60923, year: 2005, vol: 76, page: 127, stat: Journal Article,

Catechol O-methyltransferase Val158Met polymorphism in schizophrenia: differential effects of Val and Met alleles on cognitive stability and flexibility
Nolan, Karen A; Bilder, Robert M; Lachman, Herbert M; Volavka, Jan
2004 Feb;161(2):359-361, American journal of psychiatry
OBJECTIVE: The catechol O-methyltransferase (COMT) Val158Met polymorphism has been associated with cognitive and behavioral phenotypes in schizophrenia. Whether COMT genotype is beneficial may depend on phenotype definition. The authors examined the effects of COMT genotype on a task that distinguishes imitation from reversal learning. They hypothesized that the Val and Met alleles would be associated with deficits in imitation learning and reversal learning, respectively. METHOD: Twenty-six patients with schizophrenia and schizoaffective disorder completed a task requiring alternation between imitation and reversal rules. RESULTS: Met homozygotes showed better acquisition of the imitation rule but greater deficit shifting from imitation to reversal. Val homozygotes had poorer imitation performance and slower reaction times. CONCLUSIONS: The Met allele, by increasing tonic dopamine, may promote cognitive stability but limit cognitive flexibility
— id: 43009, year: 2004, vol: 161, page: 359, stat: Journal Article,

Catecholamines and Aggression: The Role of COMT and MAO Polymorphisms
Volavka, Jan; Bilder, Robert; Nolan, Karen
2004 Dec;1036:393-398, Annals of the New York Academy of Sciences
Catecholaminergic systems are involved in the regulation of aggressive behavior; this regulation is implemented in interactions with other neurobiological mechanisms. Most of the available evidence indicates that norepinephrine and dopamine lower the threshold for an aggressive response to environmental stimuli. Two major enzymes are responsible for catecholamine catabolism in the brain: catechol-O-methyltransferase (COMT) and monoamine oxidase A (MAOA). The transcriptional activity of the genes coding for these enzymes is governed by common functional polymorphisms. If aggressive behavior is enhanced by catecholaminergic activity, then the lower activity of COMT and MAOA (resulting in a slower inactivation of catecholamines) should indirectly enhance aggression. This prediction has been supported by most (but not all) observations in rodents and humans. Male mice that have either the COMT or the MAOA gene knocked out show elevated aggression. The allele that codes for the lower enzymatic activity of COMT has been associated with elevated aggressive behavior in several samples of psychiatric patients. Similarly, the alleles that code for the lower activity of MAOA were associated with the development of aggressive behavior in maltreated male children in a large birth cohort study. Collectively, these results suggest that COMT and MAOA polymorphisms represent a basic neurobiological mechanism that contributes to the regulation of aggressive behavior
— id: 60262, year: 2004, vol: 1036, page: 393, stat: Journal Article,

Overt aggression and psychotic symptoms in patients with schizophrenia treated with clozapine, olanzapine, risperidone, or haloperidol
Volavka, Jan; Czobor, Pal; Nolan, Karen; Sheitman, Brian; Lindenmayer, Jean-Pierre; Citrome, Leslie; McEvoy, Joseph P; Cooper, Thomas B; Lieberman, Jeffrey A
2004 Apr;24(2):225-228, Journal of clinical psychopharmacology
The subjects were 157 treatment-resistant inpatients diagnosed with chronic schizophrenia or schizoaffective disorder. They were randomly assigned to treatment with clozapine, olanzapine, risperidone, or haloperidol in a 14-week, double-blind trial. Incidents of overt aggression were recorded and their severity was scored. The Positive and Negative Syndrome Scale was administered. Atypical antipsychotics showed an overall superiority over haloperidol, particularly after the first 24 days of the study when the dose escalation of clozapine was completed. Once an adequate therapeutic dose of clozapine was reached, it was superior to haloperidol in reducing the number and severity of aggressive incidents. Patients exhibiting persistent aggressive behavior showed less improvement of psychotic symptoms than the other patients. There was an interaction between aggressiveness, medication type, and antipsychotic response: risperidone and olanzapine showed better antipsychotic efficacy in patients exhibiting less aggressive behavior; the opposite was true for clozapine. Clozapine appears to have superior antiaggresive effects in treatment-resistant patients; this superiority develops after the patient has been exposed to an adequate dose regimen
— id: 60937, year: 2004, vol: 24, page: 225, stat: Journal Article,

COMT158 polymorphism and hostility
Volavka, Jan; Kennedy, James L; Ni, Xingqun; Czobor, Pal; Nolan, Karen; Sheitman, Brian; Lindenmayer, Jean-Pierre; Citrome, Leslie; McEvoy, Joseph; Lieberman, Jeffrey A
2004 May 15;127B(1):28-29, American journal of medical genetics
The main study was designed primarily to compare the clinical effects of four antipsychotics in 157 patients with schizophrenia or schizoaffective disorder. The secondary genetic study, reported here, is based on a subset of 60 patients who consented to genotyping assays. Based on previous work with the catechol-O-methyltransferase (COMT) 158 polymorphism, we hypothesized that the Met-Met homozygotes would be more hostile than the heterozygotes and the Val-Val homozygotes. Hostility ratings at baseline were used to test this hypothesis. The Met-Met homozygotes (N = 7) were found to have significantly higher levels of hostility than the other patients (N = 53). The hypothesis was thus supported. The finding should be replicated in a larger sample
— id: 43008, year: 2004, vol: 127B, page: 28, stat: Journal Article,

Validation of a modified stroop task for fMRI studies in patients with schizophrenia
Antonius D; Nolan KA; Weiss EM
2003 ;1:25-34, New School Psychology Bulletin
— id: 104929, year: 2003, vol: 1, page: 25, stat: Journal Article,

Validation of a modified Stroop task for fMRI studies in patients with schizophrenia
Antonius, D; Nolan, KA; Weiss, EM
2003 MAR 15 ;60(1):122-122, Schizophrenia research
— id: 104920, year: 2003, vol: 60, page: 122, stat: Journal Article,

Characteristics of assaultive behavior among psychiatric inpatients
Nolan, Karen A; Czobor, Pal; Roy, Biman B; Platt, Meredith M; Shope, Constance B; Citrome, Leslie L; Volavka, Jan
2003 Jul;54(7):1012-1016, Psychiatric services
OBJECTIVE: The purpose of this study was to assess the extent to which psychosis, disordered impulse control, and psychopathy contribute to assaults among psychiatric inpatients. METHODS: The authors used a semistructured interview to elicit reasons for assaults from assailants and their victims on an inpatient research ward. Video monitoring provided supplemental information to confirm participants' identities and activities before and during the assault. RESULTS: Consensus clinical ratings indicated that approximately 20 percent of the assaults in this sample were directly related to positive psychotic symptoms. Factor analysis revealed two psychosis-related factors, one related to positive psychotic symptoms and the other to psychotic confusion and disorganization, as well as a third factor that differentiated impulsive from psychopathic assaults. CONCLUSIONS: Information obtained from interviews with assailants can reveal the underlying causes of specific assaults. This information is potentially useful in the selection of rational antiaggressive treatment strategies
— id: 60943, year: 2003, vol: 54, page: 1012, stat: Journal Article,

Aggressive behavior in schizophrenia is associated with the low enzyme activity COMT polymorphism: a replication study
Strous, Rael D; Nolan, Karen A; Lapidus, Raya; Diaz, Libna; Saito, Takuya; Lachman, Herbert M
2003 Jul 1;120B(1):29-34, American journal of medical genetics
We have previously reported that increased aggressive behavior in schizophrenic patients may be associated with a polymorphism at codon 158 of the catechol O-methyltransferase (COMT) gene that encodes a low enzyme activity variant. The finding has been replicated by one group, but not others. The discordant findings could be due to statistical errors or methodological issues in the assessment of aggressive/violent behavior. Consequently, additional studies are needed. Patients with schizophrenia (SZ) were assessed for violent behavior using the Lifetime History of Aggression (LHA) scale, an 11-item questionnaire that includes Aggression, Self-Directed Aggression, and Consequences/Antisocial Behavior subscales. DNA was genotyped for the COMT 158 polymorphism, as well as a functional polymorphism in the monoamine oxidase A (MAOA) gene promoter. Similar to our previously reported findings, a statistically significant association was found between aggressive behavior in SZ and the COMT 158 polymorphism; mean LHA scores were higher in subjects homozygous for 158Met, the low enzyme activity COMT variant (F(2,105) = 5.616, P = 0.005). Analysis of the major LHA subscales revealed that the association with 158Met was due to high scores on the Aggression, and Self-Directed Aggression subscales, but not the Consequences/Antisocial Behavior subscale. No significant association was detected for the MAOA gene alone. Our findings provide further support that COMT is a modifying gene that plays a role in determining interindividual variability in the proclivity for outward and self-directed aggressive behavior found in some schizophrenic patients
— id: 40069, year: 2003, vol: 120B, page: 29, stat: Journal Article,

Aspetti neurobiologici e correlati clinici del comportamento aggressivo in pazienti psicotici [= Neurobiological aspects and clinical correlates of aggressive behaivor in psychotic patients]
Volavka J; Citrome L; Nolan K
2003 ;127(2):121-142, Rivista sperimentale di Freniatria
— id: 40070, year: 2003, vol: 127, page: 121, stat: Journal Article,

Suicidal behavior in patients with schizophrenia is related to COMT polymorphism
Nolan KA; Volavka J; Czobor P; Cseh A; Lachman H; Saito T; Tiihonen J; Putkonen A; Hallikainen T; Kotilainen I; Rasanen P; Isohanni M; Jarvelin MR; Karvonen MK
2000 Sep;10(3):117-124, Psychiatric genetics
A common functional polymorphism that results in a three- to four-fold difference in catechol-O-methyltransferase (COMT) enzyme activity has been related to psychiatric disorders such as ultra-ultra rapid cycling bipolar disorder, drug abuse and alcoholism (Lachman et al., 1996a; Karayiorgou et al., 1997; Vandenbergh et al., 1997; Papolos et al., 1998; Tiihonen et al., 1999). Several studies have also reported associations between the allele encoding the low enzyme activity COMT variant (L allele) and other-directed aggression (Strous et al., 1997; Lachman et al., 1998; Kotler et al., 1999) in schizophrenic and schizoaffective patients. The current study investigated whether the COMT L allele is also associated with suicide attempts in schizophrenic and schizoaffective patients. COMT genotypes were determined and history of suicide attempts was retrospectively investigated in a Finnish sample (n = 94) and a US sample (n = 54). Significant associations were observed between COMT genotype and suicide; specifically, history of violent suicide attempts. The COMT L allele was more frequent in subjects who had attempted suicide by violent means. These associations were significant in males but not females. These findings support a common neurobiological substrate for self- and other-directed aggression, and suggest that catecholaminergic alterations may contribute to these behaviors in schizophrenic and schizoaffective patients
— id: 18203, year: 2000, vol: 10, page: 117, stat: Journal Article,

An association between a polymorphism of the tryptophan hydroxylase gene and aggression in schizophrenia and schizoaffective disorder
Nolan KA; Volavka J; Lachman HM; Saito T
2000 Sep;10(3):109-115, Psychiatric genetics
Serotonergic pathways have been implicated in impulsive and aggressive behavior. Polymorphisms in the regulatory region of the serotonin transporter (5-HTT), in intron 7 of the tryptophan hydroxylase (TPH) gene and in the MAOA gene were previously reported to be associated with mood and anxiety disorders, impulsivity and aggression. In this study, we analyzed these polymorphisms in men and women with schizophrenia or schizoaffective disorder (n = 84) who met our criteria for violence (history of two or more assaults on others) or nonviolence (no history of either assaultive or threatening behavior). In males, a modest association between TPH genotype and history of violence (chi-square test = 6.703, degrees of freedom = 2, P = 0.035) was not statistically significant after correction for multiple comparisons (corrected P = 0.21). The TPH L allele was more frequent in violent males (chi-square = 5.323, degrees of freedom = 1, P = 0.021) but this difference also failed to withstand correction (corrected P = 0.126). No significant associations were found for either the 5-HTT or MAOA polymorphisms in males or females. These results tend to support previous reports by New et al. (1996; 1998) of an association between the TPH L allele and impulsive aggression in males with personality disorder, but larger studies are needed
— id: 18204, year: 2000, vol: 10, page: 109, stat: Journal Article,

Violence in Schizophrenia: The Roles of Psychosis and Psychopathy
Nolan KA; Citrome L; Volavka J
1999 ; 5:326-335, Journal of practical psychiatry & behavioral health
Violence in patients with schizophrenia is a serious problem, affecting not only the patients but also their families, the providers of mental health services, and society in general. The risk for violent behavior in patients diagnosed with schizophrenia is elevated relative to patients diagnosed with other psychiatric illnesses as well as healthy individuals. The authors review the various factors that contribute to increased risk for violence in patients with schizophrenia. The increased likelihood of violence is related to the severity of psychosis and to the presence of specific psychotic symptoms. Comorbid substance abuse also contributes to violent behavior in patients with schizophrenia, as does treatment noncompliance. Emerging evidence indicates an association between comorbid psychopathy and violence in patients with schizophrenia and schizoaffective disorder. The relevance of these factors to risk assessment and treatment options for violent patients with schizophrenia is discussed
— id: 8624, year: 1999, vol: 5, page: 326, stat: Journal Article,

Psychopathy and violent behavior among patients with schizophrenia or schizoaffective disorder
Nolan KA; Volavka J; Mohr P; Czobor P
1999 Jun; 50(6):787-792, Psychiatric services
OBJECTIVE: Although a strong association between violence and psychopathy has been demonstrated in nonpsychotic forensic populations, the relationship between psychopathy and violence among patients with schizophrenia has not been thoroughly explored. Patients with and without a history of persistent violent behavior were compared for comorbidity of psychopathy and schizophrenia or schizoaffective disorder. METHODS: Violent and nonviolent patients were identified through reviews of hospital charts and records of arrests and convictions. The Psychopathy Checklist: Screening Version was administered to 51 patients, 26 violent patients and 25 matched nonviolent patients. Analysis of variance was used as the principal statistical method for comparing violent and nonviolent groups. RESULTS: Mean psychopathy scores were higher for violent patients than nonviolent patients. Five of the violent patients (19 percent) had scores exceeding the cutoff for psychopathy, and 13 (50 percent) scored in the possible psychopathic range. All of the nonviolent patients scored below the cutoff for possible psychopathy. Higher psychopathy scores were associated with earlier age of onset of illness and more arrests for both violent and nonviolent offenses. CONCLUSIONS: The comorbidity of schizophrenia and psychopathy was found to be higher among violent patients than among nonviolent patients. Violent patients with schizophrenia who score high on measures of psychopathy may have a personality disorder that precedes the emergence of psychotic symptoms, or they may constitute a previously unclassified subtype of schizophrenia, characterized by early symptoms of conduct disorder symptoms and persistent violent behavior
— id: 8609, year: 1999, vol: 50, page: 787, stat: Journal Article,

Association between catechol O-methyltransferase genotype and violence in schizophrenia and schizoaffective disorder
Lachman HM; Nolan KA; Mohr P; Saito T; Volavka J
1998 Jun; 155(6):835-837, American journal of psychiatry
OBJECTIVE: The authors previously reported a relationship between an allele encoding the low activity variant of catechol O-methyltransferase (COMT) and aggressive behavior in schizophrenic patients. This study replicates and extends these findings by using more direct measures of violent behavior. METHOD: Fifty-five white patients (34 men, 21 women) with DSM-IV diagnoses of schizophrenia or schizoaffective disorder were selected to form two groups (violent and nonviolent) on the basis of history of aggressive behavior. COMT genotypes were determined by restriction fragment length polymorphism analysis. RESULTS: A significant association was found between COMT genotype and history of violent behavior. Sixty-four percent of patients homozygous for the low-activity COMT allele were violent; 80% of patients homozygous for the high-activity allele were nonviolent. CONCLUSIONS: The gene determining the activity of an important regulatory enzyme in catecholamine inactivation is associated with violent behavior in patients with schizophrenia and schizoaffective disorder
— id: 8610, year: 1998, vol: 155, page: 835, stat: Journal Article,

Incidence of the Fuld WAIS-R Profile in Traumatic Brain Injury and Parkinson's Disease
Nolan KA; Burton LA
1998 Jul;13(5):425-432, Archives of clinical neuropsychology
THE FREQUENCY OF OCCURRENCE OF THE FULD PROFILE FOR CHOLINERGIC DEFICIENCY WAS INVESTIGATED IN TWO CLINICAL POPULATIONS: inpatients who had suffered traumatic brain injury and outpatients who carried a diagnosis of Parkinson's disease. The observed incidence of positive Fuld profiles was not significantly different in the two groups, 14% in the traumatic brain injury group and 24% in the Parkinson's disease group. These findings are consistent with recent reviews of the sensitivity and specificity of the Fuld profile in various clinical and nonclinical populations. The generally low sensitivity of the Fuld profile does not support its usefulness in the differential diagnosis of dementia. However, it may serve as an indicator of cholinergic deficiency, which could be used to select patients who would be likely to respond to cholinomimetic therapies
— id: 39011, year: 1998, vol: 13, page: 425, stat: Journal Article,

Absence of vascular dementia in an autopsy series from a dementia clinic [see comments]
Nolan KA; Lino MM; Seligmann AW; Blass JP
1998 May; 46(5):597-604, Journal of the American Geriatrics Society
OBJECTIVE: The role of cerebrovascular disease in dementia in older people has been the subject of controversy. This study was undertaken to examine the prevalence of vascular disease in a prospective autopsy series of patients with clinically diagnosed dementia. DESIGN: Structured review of clinical and neuropathological examinations. Clinical diagnoses were assigned in accordance with the recommendations of the NINCDS/ADRDA consensus panel. Neuropathological examinations were performed at an academic neuropathology service using published consensus criteria for the diagnosis of Alzheimer's disease and other forms of dementia. SETTING: A subspecialty, outpatient dementia clinic in a university-affiliated suburban American hospital. PARTICIPANTS: Eighty-seven unselected patients coming to autopsy who had undergone clinical dementia evaluation. RESULTS: Dementia could not be attributed to the effects of cerebrovascular disease alone in any of the 87 patients coming to autopsy. Seventy-six (87%) of the patients were found to have Alzheimer's disease (AD), 44 had AD alone, and 32 had AD in combination with cerebrovascular disease (CVD). All of the patients with signs of CVD at autopsy were also found to have some concomitant neurodegenerative disease. The absence of patients in whom vascular dementia could be diagnosed at neuropathology was not the result of recruitment bias. CONCLUSION: Clinicians should maintain a high index of suspicion of AD or other neurodegenerative process in older patients whose presenting complaint is dementia, even in the presence of well documented cerebrovascular disease
— id: 8611, year: 1998, vol: 46, page: 597, stat: Journal Article,

"Incidence of the Fuld WAIS-R profile in traumatic brain injury and Parkinson's disease": Erratum
Nolan, Karen A; Burton, Leslie A
1998 Nov;13(8):751-751, Archives of clinical neuropsychology
Reports an error in the original article by K. A. Nolan and L. A. Burton (Archives of Clinical Neuropsychology, 1998, 13(5), 425-432). Due to a typesetting error, the Fuld Formula that appeared was incorrectly printed. The corrected formula is supplied. (The following abstract of this article originally appeared in record 1998-04288-002.):The frequency of occurrence of the Fuld Wechsler Adult Intelligence Scale~~Revised (WAIS~~R) profile for cholinergic deficiency was investigated in 2 clinical populations: 50 inpatients (aged 16-49 yrs) who had suffered traumatic brain injury and 59 outpatients (aged 42-80 yrs) diagnosed with Parkinson's disease. The observed incidence of positive Fuld profiles was not significantly different in the 2 groups (14% and 24%, respectively). These findings are consistent with recent reviews of the sensitivity of the Fuld profile in various clinical and nonclinical populations. The generally low sensitivity of the Fuld profile does not support its usefulness in the differential diagnosis of dementia. However, it may serve as an indicator of cholinergic deficiency, which could be used to select patients who would be likely to respond to cholinomimetic therapies.
— id: 8623, year: 1998, vol: 13, page: 751, stat: Journal Article,

The continuum of deep/surface dyslexia
Nolan KA; Volpe BT; Burton LA
1997 Jul; 26(4):413-424, Journal of psycholinguistic research
A right-handed male sustained traumatic brain injury which resulted in anomia, dyslexia and agraphia. The most severe CT (computed tomography)-identified brain damage was located in the right parieto-temporal lobe. In the first months following the injury, the pattern of reading errors was similar to that associated with deep dyslexia. However, nonlexical derivation of phonology from print was not abolished. As the patient's ability to associate letter patterns with sounds improved, oral reading also improved. Although he no longer produced semantic errors in oral reading, he continued to produce oral reading errors that were visually and phonologically related to the targets. Four months after the injury, the error pattern observed in the patient's oral reading was consistent with very mild surface dyslexia. The significance of these observations to dual-deficit models of acquired dyslexia is discussed, as are their implications for rehabilitation
— id: 8612, year: 1997, vol: 26, page: 413, stat: Journal Article,

Violent crime in psychiatric patients: relationship to frontal lobe impairment
Krakowski M; Czobor P; Carpenter MD; Nolan K; Libiger J; Kunz M; Papezova H; Parker BB; Schmader L
1996 ;17:53-59, American journal of forensic psychiatry
— id: 18207, year: 1996, vol: 17, page: 53, stat: Journal Article,

Reduced heart rate response to nortriptyline in females with unipolar depression
Pomara, N; Deptula, D; Nolan, K; Tun, H; Singh, R; Leviste, F; Cooper, TB
1996 APR 1 ;39(7):427-427, Biological psychiatry
— id: 52983, year: 1996, vol: 39, page: 427, stat: Journal Article,

Differential effects of alprazolam and lorazepam on plasma cortisol in normal elderly
Pomara, N; Deptula, D; Nolan, K; Tun, H; Singh, R; Leviste, F; Ritchie, J; Greenblatt, DJ; Nemeroff, CB
1996 APR 1 ;39(7):428-428, Biological psychiatry
— id: 52984, year: 1996, vol: 39, page: 428, stat: Journal Article,

Scopolamine-induced impairment as a potential predictor of Alzheimer's disease in individuals with Apolipoprotein E type 4 alleles
Pomara N; Nolan K; Halpern G
1995 Dec;20(12):1519-1520, Neurochemical research
— id: 18206, year: 1995, vol: 20, page: 1519, stat: Journal Article,

THE EFFECT OF NORTRIPTYLINE ON VERBAL RECALL
POMARA, N; NOLAN, K; DEPTULA, D; PESELOW, E; COOPER, TB
1995 MAY 1 ;37(9):611-611, Biological psychiatry
— id: 87283, year: 1995, vol: 37, page: 611, stat: Journal Article,

Screening for dementia in family practice
Nolan KA; Mohs RC
Alzheimer's disease: a guide to practical management St. Louis: Mosby, 1994,
— id: 2598, year: 1994, vol: , page: ?, stat: Chapter,

CERAD part VII: accuracy of reporting dementia on death certificates of patients with Alzheimer's disease
Raiford K; Anton-Johnson S; Haycox Z; Nolan K; Schaffer A; Caimano C; Fillenbaum G; Heyman A
1994 Nov;44(11):2208-2209, Neurology
— id: 18205, year: 1994, vol: 44, page: 2208, stat: Journal Article,

Failure of CT scan to detect ischemic lesions in patients with dementia
Kurita A; Black RS; Blass JP; Deck MD; Nolan KA
1993 Oct-Dec; 6(4):245-250, Journal of geriatric psychiatry & neurology
Although clinical series have described relatively high accuracy in the ability of computed tomographic (CT) scan to detect significant cerebrovascular damage in patients with dementia, a recent neuropathologically controlled study failed to document that relationship. We now present clinical, neuroradiologic (CT), and neuropathologic information on four patients in whom CT scans did not contribute to the diagnosis of multi-infarct dementia or mixed dementia, despite clinical and neuropathologic evidence of infarcts. In one patient, the failure of CT scan to detect ischemic lesions may be attributable to less sensitive neuroradiologic criteria in use at the time of the examination. In the other three, even neuroradiologic review after the pathology was known failed to reveal the infarcts. These observations suggest the advisability of caution in using CT scan as a criterion for the presence or absence of cerebrovascular damage in patients with dementia
— id: 8613, year: 1993, vol: 6, page: 245, stat: Journal Article,

Relationship between cognitive status and behavioral symptoms in Alzheimer's disease and mixed dementia
Kurita A; Blass JP; Nolan KA; Black RS; Thaler HT
1993 Jul; 41(7):732-736, Journal of the American Geriatrics Society
OBJECTIVE: To investigate the relationship between cognitive and behavioral impairments in Alzheimer's disease (AD) and to examine whether the addition of cerebrovascular disease modifies that relationship. DESIGN: Correlational analysis. SETTING: An outpatient dementia clinic. PATIENTS: An autopsy-confirmed series of 28 patients with AD and 16 patients with mixed Alzheimer and vascular dementia (MIX). MEASUREMENTS: Neuropsychological and behavioral tests during life: Mini-Mental State (MMS), Blessed Dementia Scale (BDS), Haycox Dementia Behavior Scale (HDBS), and two non-cognitive functional scales derived from the BDS and HDBS. RESULTS: In the AD group, MMS scores correlated significantly with scores on the BDS, HDBS, and two non-cognitive functional scales. In the MIX group, however, no significant relationship was observed between MMS scores and scores on any of the behavioral measures. CONCLUSIONS: These observations suggest that in AD, cognitive and behavioral impairments progress simultaneously. However, with the addition of a vascular component to the dementing process, cognitive and behavioral impairments may progress more independently
— id: 8614, year: 1993, vol: 41, page: 732, stat: Journal Article,

Pentoxifylline in cerebrovascular dementia
Black RS; Barclay LL; Nolan KA; Thaler HT; Hardiman ST; Blass JP
1992 Mar; 40(3):237-244, Journal of the American Geriatrics Society
OBJECTIVE: To test the effect of pentoxifylline, a hemorheologic agent used to treat intermittent claudication, on the course of vascular dementia. DESIGN: Randomized, double-blind, placebo-controlled, parallel group trial. SETTING: Outpatient tertiary care center. PATIENTS: 64 patients meeting DSM-III criteria for multi-infarct dementia with modified Hachinski ischemic scores greater than or equal to 6, 38 of whom completed the trial. INTERVENTION: Pentoxifylline (Trental) 400 milligram tablets three times daily vs placebo for 36 weeks. MAIN OUTCOME MEASURE: Alzheimer's Disease Assessment Scale (ADAS). RESULTS: Baseline demographic values and psychometric variables were similar in the placebo and control groups; endpoint statistical analysis was used to allow the use of data from all patients in this clinically high-risk group. For the total group, the slowing of deterioration did not reach statistical significance (by 2-tailed t test), as measured by scores on the total ADAS (P = 0.058) or on the cognitive (ADAS items 1-11; P = 0.064) or non-cognitive subscales (ADAS items 12-21; P = 0.234), although it was significant on the cognitive subscales excluding memory (ADAS items 2-6, 8-10; P = 0.036). For the subgroup of 40 patients who had CT and/or MRI evidence of stroke as well as meeting the other inclusion criteria, treatment with pentoxifylline was associated with significantly slower deterioration, as measured by the total ADAS (P = 0.023) and cognitive subscores (P = 0.020) but not non-cognitive subscores (P = 0.118). For the subgroup of 37 patients who had at least one discrete clinical stroke, treatment with pentoxifylline was associated with significantly less deterioration on the total ADAS (P = 0.002) and both the cognitive (P = 0.001) and non-cognitive (P = 0.017) subscores. CONCLUSION: Treatment with pentoxifylline may slow the progression of dementia in patients who meet DSM-III criteria for 'multi-infarct dementia' and who also have clinical and neuroradiological evidence of cerebrovascular disease
— id: 8615, year: 1992, vol: 40, page: 237, stat: Journal Article,

Preventing cognitive decline
Nolan KA; Blass JP
1992 Feb; 8(1):19-34, Clinics in geriatric medicine
Many studies of age-related cognitive decline have failed to distinguish between usual and successful aging. Although some degree of cognitive impairment is associated with aging, when one looks at average performance, there is great variability among individuals, with many showing little or no deleterious effects of aging on intellectual abilities. Many of the risk factors for dementia and for conditions associated with cognitive impairments can be treated or controlled. Among the preventable causes of cognitive decline are the following: AIDS, Alcohol and drug abuse, Cerebrovascular disease, Exposure to organic solvents or lead, Head trauma, Overmedication, Syphilis. Other conditions that may cause cognitive decline can be controlled or treated: Atherosclerosis, Depression, Diabetes, Emphysema, High blood pressure, Obesity, Sleep disorders, Thyroid dysfunction. In addition, it may be possible to enhance the cognitive performance of even healthy elderly people through changes in diet and lifestyle. Recent data raise the possibility that improved prenatal and perinatal care and greater access to educational opportunities may result in a decreased incidence of dementia in future generations of older adults. Although they are rapidly becoming more numerous, the efficacy of cognitive training programs in preventing or slowing cognitive decline has not yet been demonstrated. Nevertheless, such programs may ameliorate cognitive impairment by reducing the psychiatric disabilities associated with anxiety and depression. The general principle underlying these strategies for limiting cognitive impairment with age is to maximize brain reserve and minimize brain damage
— id: 8616, year: 1992, vol: 8, page: 19, stat: Journal Article,

Delirium: phenomenology and diagnosis--a neurobiologic view
Blass JP; Nolan KA; Black RS; Kurita A
1991 Winter; 3(2):121-134, International psychogeriatrics
'Delirium' is a reversible confusional state. It results from widespread but reversible interference with the function of cortical neurons, as documented by diffuse slowing on EEG and decreases in cerebral metabolic rate. Delirium can be due to impairments in neuronal metabolism, in neurotransmission (notably cholinergic), or in input from subcortical structures. Engel and Romano (1959) formulated delirium and dementia as the two poles of a spectrum of 'cerebral insufficiency,' with delirium resulting from reversible functional impairment and dementia from irreversible anatomic damage. So many disorders can precipitate delirium that the differential diagnosis tests every facet of one's knowledge of medicine. With aging, both normative changes in the brain and the increasing incidence of brain diseases predispose to the development of delirium. The brain damage responsible for a dementia can sensitize to the development of a superimposed delirium
— id: 8618, year: 1991, vol: 3, page: 121, stat: Journal Article,

A trial of thiamine in Alzheimer's disease
Nolan KA; Black RS; Sheu KF; Langberg J; Blass JP
1991 Jan; 48(1):81-83, Archives of neurology
Because a previous short-term study demonstrated a statistically significant, but not clinically important, improvement in cognitive test scores during thiamine treatment in patients with dementia of the Alzheimer's type, a 12-month, double-blind, parallel-group study was conducted to examine whether long-term administration of thiamine at 3 g/d might slow the progression of dementia of the Alzheimer's type. Fifteen subjects were enrolled and 10 completed the 1-year study. Data are available for two additional subjects through the first 9 months of study. No significant differences were found between the placebo and thiamine groups at any point during the study. In both groups, overall means for the Mini-Mental State Examination, verbal learning, and naming scores decreased significantly over the 12-month study period. These results do not support the hypothesis that long-term administration of thiamine at 3 g/d might slow the progression of dementia of the Alzheimer's type
— id: 8617, year: 1991, vol: 48, page: 81, stat: Journal Article,

White matter in the elderly
Nolan KA; Blass JP
1990 Sep; 40(9):1480-1480, Neurology
— id: 8619, year: 1990, vol: 40, page: 1480, stat: Journal Article,

An analysis of writing in a case of deep dyslexia
Nolan KA; Caramazza A
1983 Nov; 20(2):305-328, Brain & language
In tests of her ability to produce written and spoken language, this deep dyslexic patient produced semantic, visual, and derivational errors, including functor substitutions, and exhibited part-of-speech and abstractness effects in oral reading, oral and written naming, and writing to dictation, but not in repetition of single words and copying from memory. This patient therefore provides confirmation of the hypothesis presented in Nolan and Caramazza (1982) that the defining symptoms of deep dyslexia will be observed in responses to any task which requires lexical mediation. The patient's written responses in all tasks but direct copying were characterized by spelling errors which included transpositions, omissions, substitutions, and additions of letters. A model of writing is proposed which explains these errors in terms of a disruption of a phoneme-grapheme conversion process which normally functions to prevent decay of information from a Graphemic Buffer.
— id: 8620, year: 1983, vol: 20, page: 305, stat: Journal Article,

Modality-independent impairments in word processing in a deep dyslexic patient
Nolan KA; Caramazza A
1982 Jul; 16(2):237-264, Brain & language
— id: 8621, year: 1982, vol: 16, page: 237, stat: Journal Article,

Spontaneous segmentation in normal and in time-compressed speech
Wingfield A; Nolan KA
1980 Aug; 28(2):97-102, Perception & psychophysics
— id: 8622, year: 1980, vol: 28, page: 97, stat: Journal Article,