Adam Wolkin, M.D.

FDG-PET and MRI imaging of the effects of sertindole and haloperidol in the prefrontal lobe in schizophrenia
Buchsbaum, Monte S; Haznedar, Mehmet; Newmark, Randall E; Chu, King-Wai; Dusi, Nicola; Entis, Jonathan J; Goldstein, Kim E; Goodman, Chelain R; Gupta, Adarsh; Hazlett, Erin; Iannuzzi, James; Torosjan, Yuliya; Zhang, Jane; Wolkin, Adam
2009 Oct;114(1-3):161-171, Schizophrenia research
Sertindole, a 2nd generation antipsychotic with low movement disorder side effects, was compared with haloperidol in a 6-week crossover study. Fifteen patients with schizophrenia (mean age=42.6, range=22-59, 11 men and 4 women) received sertindole (12-24 mg) or haloperidol (4-16 mg) for 6 weeks and then received a FDG-PET scan and an anatomical MRI. Patients were then crossed to the other treatment and received a second set of scans at week 12. Dose was adjusted by a physician blind to the medication type. Brodmann areas were identified stereotaxically using individual MRI templates applied to the coregistered FDG-PET image. Sertindole administration was associated with higher dorsolateral prefrontal cortex metabolic rates than haloperidol and lower orbitofrontal metabolic rates than haloperidol. This effect was greatest for gray matter of the dorsolateral Brodmann areas 8, 9, 10, 44, 45, and 46. Patients were further contrasted with an approximately age and sex-matched group of 33 unmedicated patients with schizophrenia and with a group of 55 normal volunteers. Sertindole administration was associated with greater change toward normal values and away from the values found in the unmedicated comparison group for dorsolateral prefrontal cortex gray matter and white matter underlying medial prefrontal and cingulate cortex. These results are consistent with the low motor side-effect profile of sertindole, greater improvement on prefrontal cognitive tasks with sertindole than haloperidol, and with the tendency of 2nd generation antipsychotic drugs to have greater frontal activation than haloperidol
— id: 138039, year: 2009, vol: 114, page: 161, stat: Journal Article,

Inferior frontal white matter anisotropy and negative symptoms of schizophrenia: a diffusion tensor imaging study
Wolkin, Adam; Choi, Steven J; Szilagyi, Sandor; Sanfilipo, Michael; Rotrosen, John P; Lim, Kelvin O
2003 Mar;160(3):572-574, American journal of psychiatry
OBJECTIVE: The purpose of this study was test the hypothesis that abnormalities of inferior frontal white matter are related to the negative symptoms of schizophrenia. METHOD: Fractional anisotropy of white matter tracts in the prefrontal area of 10 schizophrenic patients was determined by diffusion tensor imaging. Patients were also assessed for severity of negative symptoms by using the Schedule for the Assessment of Negative Symptoms (SANS). RESULTS: Inferior frontal white matter fractional anisotropy was significantly inversely correlated with the SANS global ratings of negative symptoms. CONCLUSIONS: These data, while preliminary, suggest that impaired white matter integrity in the inferior frontal region may be associated with the severity of negative symptoms in schizophrenia
— id: 94337, year: 2003, vol: 160, page: 572, stat: Journal Article,

A neuropathology of psychosis?
Wolkin, Adam; Rusinek, Henry
2003 Jan 25;361(9354):270-271, Lancet
— id: 73260, year: 2003, vol: 361, page: 270, stat: Journal Article,

Reduced frontal white matter integrity in cocaine dependence: a controlled diffusion tensor imaging study
Lim, Kelvin O; Choi, Steven J; Pomara, Nunzio; Wolkin, Adam; Rotrosen, John P
2002 Jun 1;51(11):890-895, Biological psychiatry
BACKGROUND: In vivo magnetic resonance studies have found that cocaine dependence is associated with T2 signal hyperintensities and metabolite abnormalities in cerebral white matter (WM). Functional neuroimaging studies have suggested that chronic cocaine use is primarily associated with frontal lobe deficits in regional cerebral blood flow and brain glucose metabolism levels; however, the effects of cocaine dependence, if any, on frontal WM microstructure are unknown. Thus, we sought to examine the effects of cocaine dependence on frontal WM integrity. METHODS: Diffusion tensor imaging was employed to examine the WM integrity of frontal regions at four levels: 10 mm above, 5 mm above, 0 mm above, and 5 mm below the anterior commissure-posterior commissure (AC-PC) plane. The fractional anisotropy (FA) of 12 cocaine-dependent patients and 13 age-similar control subjects was compared. RESULTS: The cocaine-dependent patients had significantly reduced FA in the frontal WM at the AC-PC plane and a trend toward reduced FA at 5 mm below the AC-PC plane, suggestive of reduced WM integrity in these regions. CONCLUSIONS: These findings were consistent with the hypothesis that cocaine dependence involves alterations in orbitofrontal connectivity, which may be involved in the decision-making deficits seen in this disorder
— id: 32117, year: 2002, vol: 51, page: 890, stat: Journal Article,

Cognitive performance in schizophrenia: relationship to regional brain volumes and psychiatric symptoms
Sanfilipo, Michael; Lafargue, Todd; Rusinek, Henry; Arena, Luigi; Loneragan, Celia; Lautin, Andrew; Rotrosen, John; Wolkin, Adam
2002 Nov 30;116(1-2):1-23, Psychiatry research
In an all-male sample of schizophrenic patients stabilized by medication (n=62) and normal controls (n=27), we obtained neuropsychological test data and high-resolution whole brain magnetic resonance scans, as well as detailed psychiatric rating scales on a subset of the patients (n=47). Schizophrenic patients had significantly worse overall age-adjusted cognitive performance than normal controls (average z-score=-0.90, range=-0.60 to -1.81), which included relatively more severe deficits with different types of memory, psychomotor speed, verbal fluency and verbal abstraction. Schizophrenic patients also had significantly smaller bilateral volumes in gray but not white matter in the prefrontal region, superior temporal gyrus and whole temporal lobe, but no group differences were observed in the hippocampus and parahippocampus. Correlations between the brain regions and cognitive performance revealed different sets of significant relationships for the two groups, particularly in the prefrontal and hippocampal regions. In addition, inverse correlations were observed between certain cognitive abilities (psychomotor speed, cognitive flexibility and verbal fluency) and patients' psychiatric ratings, especially with measures of negative symptoms. The convergence of findings for schizophrenic patients regarding the prefrontal region, negative symptoms, psychomotor speed and cognitive flexibility suggests that schizophrenic negative symptoms may involve disruption of frontal-subcortical connections
— id: 73261, year: 2002, vol: 116, page: 1, stat: Journal Article,

Cardiovascular Effects of 0.5 Milligrams per Kilogram Oral d-Amphetamine and Possible Attenuation by Haloperidol
Angrist B; Sanfilipo M; Wolkin A
2001 May-Jun;24(3):139-144, Clinical neuropharmacology
SUMMARY: In a series of earlier studies, an oral dose of 0.5 mg/kg d-amphetamine was administered to 81 patients with schizophrenia and eight normal control subjects. Seven more subjects with schizophrenia received placebo. Blood pressure and pulse rate were monitored before and 3 hours after drug administration. Blood pressure increased in both amphetamine groups, whereas placebo had no effect. However, pulse rate did not change in the schizophrenic group and only increased after 3 hours in normal control subjects as blood pressure began to decrease. Significant negative correlations between systolic blood pressure and pulse rate occurred at 2 and 3 hours, suggesting that the early cardiovascular response to amphetamine is an increase in blood pressure that recruits reflex control of heart rate. Eighteen of these subjects had hypertensive responses. Six subjects received 5 mg haloperidol intramuscularly, and 12 others had their blood pressure monitored until normalization. Haloperidol led to a more rapid decline of some but not all indices of blood pressure, suggesting that amphetamine-induced hypertension may have a dopaminergic component
— id: 20630, year: 2001, vol: 24, page: 139, stat: Journal Article,

Fine volumetric analysis of the cerebral ventricular system in schizophrenia: further evidence for multifocal mild to moderate enlargement
Sanfilipo M; Lafargue T; Arena L; Rusinek H; Kushner K; Lautin A; Loneragan C; Vaid G; Rotrosen J; Wolkin A
2000 ;26(1):201-216, Schizophrenia bulletin
We used traditional volumetric regional analysis and a finer anterior-posterior (AP) profile volumetric analysis to examine the cerebral ventricular system in an all-male, demographically matched sample of schizophrenia patients (n = 73) and normal controls (n = 29) using 2.8-mm-thin coronal T1-weighted magnetic resonance images from a 1.5 tesla scanner. Traditional regional analysis was performed on various regions using absolute volumes after adjusting for intracranial volume (ICV) and age. The fine AP profile analysis was done by intrasubject 'stacking' of contiguous coronal cross-sectional volumes (adjusted for ICV and age) across the AP plane, intersubject AP alignment of all slices relative to the mammillary bodies, and plotting of slice volumes along the AP plane with 95 percent t-test-based confidence intervals. Schizophrenia subjects had mild to moderate multifocal ventricular enlargement (overall effect size d = 0.48), which was especially prominent in the right posterior temporal horn and, more generally, in the central to posterior portions of the lateral and third ventricles. Schizophrenia subjects also had milder enlargement in the left frontal horn, but no significant differences were found in the anterior temporal horns and the right frontal horn. Post hoc analyses of demographic, clinical, and neuropsychological variables did not account for much variance in the ventriculomegaly observed in the schizophrenia group. The lack of a single locus in the observed ventricular enlargement, the nonsignificant results from schizophrenia subtypes based on regional distributions, and the strong positive correlations among the ventricular regions for the schizophrenia group suggest that the ventriculomegaly seen in this chronic population reflects a single brainwide disease process leading to a multifocal or patchy loss of integrity in brain structure
— id: 23575, year: 2000, vol: 26, page: 201, stat: Journal Article,

Volumetric measure of the frontal and temporal lobe regions in schizophrenia: relationship to negative symptoms
Sanfilipo M; Lafargue T; Rusinek H; Arena L; Loneragan C; Lautin A; Feiner D; Rotrosen J; Wolkin A
2000 May;57(5):471-480, Archives of general psychiatry
BACKGROUND: Previous research has provided evidence for brain abnormalities in schizophrenia, but their relationship to specific clinical symptoms and syndromes remains unclear. METHODS: With an all-male demographically similar sample of 53 schizophrenic patients and 29 normal control subjects, cerebral gray and white matter volumes (adjusted for intracranial volume and age were determined for regions in the prefrontal lobe and in the superficial and mesial temporal lobe using T1-weighted magnetic resonance imaging with 2.8-mm coronal slices. RESULTS: As a group, schizophrenic patients had wide-spread bilateral decrements in gray matter in the pre-frontal (7.4%) and temporal lobe regions (8.9%), but not in white matter in these regions. In the temporal lobe, gray matter reductions were found bilaterally in the superior temporal gyrus (6.0%), but not in the hippocampus and parahippocampus. While there were no overall group differences in white matter volumes, widespread decrements in prefrontal white matter in schizophrenic patients (n = 53) were related to higher levels of negative symptoms (partial r[49] = -0.42, P = .002), as measured by the Scale for the Assessment of Negative Symptoms. A post hoc analysis revealed that schizophrenic patients with high negative symptoms had generalized prefrontal white matter reductions (11.4%) that were most severe in the orbitofrontal subregion (15.1%). CONCLUSIONS: These results suggest that gray matter deficits may be a fairly common structural abnormality of schizophrenia, whereas reductions in prefrontal white matter may be associated with schizophrenic negative symptoms
— id: 23576, year: 2000, vol: 57, page: 471, stat: Journal Article,

Effect of a haloperidol challenge on regional brain metabolism in neuroleptic-responsive and nonresponsive schizophrenic patients
Bartlett EJ; Brodie JD; Simkowitz P; Schlosser R; Dewey SL; Lindenmayer JP; Rusinek H; Wolkin A; Cancro R; Schiffer W
1998 Mar;155(3):337-343, American journal of psychiatry
OBJECTIVE: The CNS metabolic response to a neuroleptic challenge in treatment-responsive and nonresponsive schizophrenic patients was measured in order to examine the relation between treatment outcome and the capacity to alter neurochemical function in response to acute receptor blockade. METHOD: Positron emission tomography (PET) and [18F]fluorodeoxyglucose (FDG) were used to measure regional cerebral metabolism in seven schizophrenic patients judged to have been responsive to drug treatment previously and seven nonresponsive schizophrenic patients after a drug-free period of at least 3 weeks (baseline) and again 12 hours after administration of 5.0 mg of haloperidol. RESULTS: The haloperidol challenge caused widespread decreases in absolute metabolism in the nonresponsive patients but not the responsive patients. These group differences reflect the findings on the second (challenge) scans, since metabolic values at baseline were not statistically different in the two groups. The pattern of decreased metabolic activity in the nonresponders after the haloperidol challenge is similar to that previously observed in normal subjects. CONCLUSIONS: The metabolic response to drug challenge separates treatment responders from nonresponders and normal subjects. The results suggest that subtyping of schizophrenia (and other psychiatric disorders) can be achieved by measuring the physiologic response to a pharmacologic challenge in vivo with chemical brain-imaging techniques
— id: 7497, year: 1998, vol: 155, page: 337, stat: Journal Article,

Fronto-striatal circuits assessed by positron emission tomography in patients treated with atypical neuroleptics, typical neuroleptics, and fenfluramine
Buchsbaum, MS; Wolkin, A; Hazlett, E; Fallon, J; Guich, S; Gupta, A; Siever, L; McCarthy, BG
1998 APR 15 ;43(4):73-18, Biological psychiatry
— id: 98349, year: 1998, vol: 43, page: 73, stat: Journal Article,

Inter-subject coregistration of brain images : a phantom study
Rusinek H; Tsui W-H; Sanfilipo M; Wolkin A
1998 ;3338:61-69, Medical imaging. Image processing (SPIE)
— id: 73287, year: 1998, vol: 3338, page: 61, stat: Journal Article,

Structural magnetic resonance image averaging in schizophrenia
Wolkin A; Rusinek H; Vaid G; Arena L; Lafargue T; Sanfilipo M; Loneragan C; Lautin A; Rotrosen J
1998 Aug;155(8):1064-1073, American journal of psychiatry
OBJECTIVE: Intersubject averaging of structural magnetic resonance (MR) images has been infrequently used as a means to study group differences in cerebral structure throughout the brain. In the present study, the authors used linear intersubject averaging of structural MR images to evaluate the validity and utility of this technique and to extend previous research, conducted using a different approach to image averaging, in which reduction in thalamic size and abnormalities in perithalamic white matter tracts in the brains of schizophrenic patients were reported by Andreasen et al. METHOD: A 1.5-T MR scanner was used to obtain high-resolution, whole brain T1-weighted structural MR images for an age-matched sample of 25 schizophrenic patients and 25 normal control subjects. A 'bounding box' procedure was used to create a single 'averaged' brain for the schizophrenic group and for the control group. Differences in signal intensity between the two average brains were examined on a pixel-wise basis through use of one-tailed effect size maps. RESULTS: Effect size maps revealed widespread patchy signal intensity differences between the two groups in both cortical and periventricular areas, including major white matter tracts. The signal intensity differences were consistent with cortical thinning/sulcal widening and ventricular enlargement. No differences were found within thalamus or in immediately surrounding white matter. Effect size maps for differences (schizophrenic minus normal subjects) had only small values. CONCLUSIONS: These results are consistent with diffuse structural brain abnormalities of both gray and white matter in schizophrenic populations such as the one in this study
— id: 23577, year: 1998, vol: 155, page: 1064, stat: Journal Article,

Time-dependent effects of a haloperidol challenge on energy metabolism in the normal human brain
Bartlett EJ; Brodie JD; Simkowitz P; Dewey SL; Rusinek H; Volkow ND; Wolf AP; Smith G; Wolkin A; Cancro R
1996 Mar 29;60(2-3):91-99, Psychiatry research
Positron emission tomography and the fluorodeoxyglucose method were used to measure regional brain metabolism before and 2 h after haloperidol (5 mg, i.m.) in 11 young normal men. These data were compared with measures obtained from nine previously studied normal men who had received no drug intervention. Although a previously published study had demonstrated significantly decreased metabolism in whole brain, neocortex, limbic cortex, thalamus, and caudate nucleus 12 h after a 5-mg dose of haloperidol, the present 2-h study did not show significant metabolic changes despite the fact that significant extrapyramidal effects occurred. Taken together, these studies demonstrate differences in the temporal organization of behavioral and metabolic responses to haloperidol challenge
— id: 12632, year: 1996, vol: 60, page: 91, stat: Journal Article,

Amphetamine and negative symptoms of schizophrenia
Sanfilipo M; Wolkin A; Angrist B; van Kammen DP; Duncan E; Wieland S; Cooper TB; Peselow ED; Rotrosen J
1996 Jan;123(2):211-214, Psychopharmacology
The purpose of this study was to assess further the effect of amphetamine on negative symptoms of schizophrenia. Thirty-seven schizophrenic males meeting DSM-III criteria were rated with the Brief Psychiatric Rating Scale, the Abrams and Taylor Scale, and the Abnormal Involuntary Movements Scale before and after double-blind administration of either amphetamine (n = 26) or placebo (n = 11). Our results indicated that amphetamine administration generally did not improve negative symptoms, even when accounting for changes in positive symptoms. However, greater baseline negative symptoms were associated with a modest diminution after amphetamine treatment. Therefore, amphetamine may modestly improve negative symptoms in those schizophrenics in whom this symptomatology is more severe
— id: 23583, year: 1996, vol: 123, page: 211, stat: Journal Article,

The study of neurotransmitter interactions using positron emission tomography and functional coupling
Schloesser R; Simkowitz P; Bartlett EJ; Wolkin A; Smith GS; Dewey SL; Brodie JD
1996 Oct;19(5):371-389, Clinical neuropharmacology
Functional brain imaging with positron emission tomography (PET) has opened up new avenues for the investigation of possible functional disturbances related to psychiatric disease as well as pharmacodynamic assessment of drug treatment in vivo. Different strategies to study pharmacologic effects on the brain have been developed in recent years. The basic methods are to measure (a) blood flow or glucose metabolism, (b) parameters of specific receptor binding, or (c) neurotransmitter metabolism. Each of these can be performed either in a resting state or after perturbation with a pharmacologic challenge. Our group has developed a general strategy for investigating pharmacologic effects on brain function: (a) determining indirect drug-induced metabolic changes with fluorodeoxyglucose PET and (b) characterizing functional interactions of neurotransmitter systems by assaying drug-induced displacement of specific receptor ligands. These study designs reflect a paradigm shift where functional coupling of brain regions and interaction of different neurotransmitter systems are seen as the basis for a multitransmitter hypothesis of schizophrenia. In this view, any disturbance in the self-regulatory process is reflected in the loss of functional interaction between systems. An overview of recent studies and their possible clinical importance will be presented
— id: 12529, year: 1996, vol: 19, page: 371, stat: Journal Article,

Blunted change in cerebral glucose utilization after haloperidol treatment in schizophrenic patients with prominent negative symptoms
Wolkin A; Sanfilipo M; Duncan E; Angrist B; Wolf AP; Cooper TB; Brodie JD; Laska E; Rotrosen JP
1996 Mar;153(3):346-354, American journal of psychiatry
OBJECTIVE: The purpose of this report was to determine 1) the effects of chronic haloperidol treatment on cerebral metabolism in schizophrenic patients, 2) the relation between negative symptoms and haloperidol-induced regional changes in cerebral glucose utilization, and 3) the relation between metabolic change and clinical antipsychotic effect. METHOD: Cerebral glucose utilization, as determined by position emission tomography (PET), was studied in 18 male schizophrenic subjects before and after chronic treatment with haloperidol at a standardized plasma level. RESULTS: Overall, haloperidol caused a widespread decrease in absolute cerebral glucose metabolism. The cerebral metabolic response to haloperidol was blunted in patients with high pretreatment negative symptom scores. CONCLUSIONS: Taken together with the results from a previously reported PET study of the effects of an acute amphetamine challenge (in which 14 of the current subjects participated), these data suggest that the negative symptom complex is associated with diminished cerebral response to change in dopaminergic activity. This deficit cannot be solely accounted for by structural differences
— id: 7060, year: 1996, vol: 153, page: 346, stat: Journal Article,

Effects of haloperidol challenge on regional cerebral glucose utilization in normal human subjects
Bartlett EJ; Brodie JD; Simkowitz P; Dewey SL; Rusinek H; Wolf AP; Fowler JS; Volkow ND; Smith G; Wolkin A
1994 May;151(5):681-686, American journal of psychiatry
OBJECTIVE: Positron emission tomography and the fluorodeoxyglucose (FDG) method were used to determine the brain's metabolic response to neuroleptic challenge in a normal, disease-free state. METHOD: FDG measurements were obtained before and 12 hours after administration of 5 mg of haloperidol to 12 young normal men. These values were compared with test-retest FDG measures obtained from nine normal male control subjects who received no drug intervention. RESULTS: After haloperidol administration, the haloperidol subjects showed significantly lower glucose utilization in the neocortex, limbic cortex, thalamus, and caudate nucleus but not in the putamen or cerebellum. After adjustment for global effects, significant reductions were still evident in the frontal, occipital, and anterior cingulate cortex, whereas the putamen and cerebellum showed significant increases. CONCLUSIONS: This study, measuring the brain's metabolic response to acute receptor blockade, is a first step in the development of an assay of CNS pharmacological activity. By determining the response to neuroleptic challenge in a normal state, the study establishes a comparison group for determining response to challenge in various psychiatric conditions
— id: 6319, year: 1994, vol: 151, page: 681, stat: Journal Article,

Diminished cerebral metabolic response to motor stimulation in schizophrenics: a PET study
Guenther, W; Brodie, J D; Bartlett, E J; Dewey, S L; Henn, F A; Volkow, N D; Alper, K; Wolkin, A; Cancro, R; Wolf, A P
1994 ;244(3):115-125, European archives of psychiatry & clinical neuroscience
Positron emission tomography (PET) and the deoxyglucose method were used to measure cerebral metabolism in 14 normals and 13 schizophrenics at rest and during performance of simple and complex finger-movement sequences. The normals, but not the schizophrenics, showed significant metabolic activation in mesial frontal and contralateral sensorimotor and premotor regions during the complex movement. The relative metabolism of schizophrenics was significantly lower than normal in frontal regions and higher than normal in thalamus and basal ganglia under all scanning conditions. The results suggest that schizophrenics may have a brain dysfunction which limits their capacity to produce a focal metabolic response to stimulation in several functionally distinct brain regions
— id: 76242, year: 1994, vol: 244, page: 115, stat: Journal Article,

Persistent psychosis after reduction in pre- and post-synaptic dopaminergic function
Wolkin A; Duncan E; Sanfilipo M; Wieland S; Cooper TB; Rotrosen J
1994 ;95(1):49-61, Journal of neural transmission
The purpose of this study was to evaluate the hypothesis that neuroleptic non-response in the face of 'adequate' DA post-synaptic receptor blockade reflects failure of regulatory mechanisms to decrease DA pre-synaptic activity. Eight chronic schizophrenics, meeting rigorous criteria for neuroleptic non-response, were treated for four weeks with alpha-methylparatyrosine as an adjunct to their previously stable neuroleptic dose. Treatment with AMPT produced a prompt decrease in plasma HVA that was, on average, 72% lower at the end of the study. While there was also strong clinical evidence of reduction in central dopaminergic activity (both a significant reduction in dyskinetic movements and increase in extrapyramidal symptoms), there was virtually no change in severity of psychotic symptoms. Thus, in this group of non-responders, psychotic symptoms persisted despite both extensive dopamine post-synaptic receptor blockade and marked reduction of presynaptic activity. These symptoms may not be directly DA dependent
— id: 23584, year: 1994, vol: 95, page: 49, stat: Journal Article,

Acute d-amphetamine challenge in schizophrenia: effects on cerebral glucose utilization and clinical symptomatology
Wolkin A; Sanfilipo M; Angrist B; Duncan E; Wieland S; Wolf AP; Brodie JD; Cooper TB; Laska E; Rotrosen JP
1994 Sep 1;36(5):317-325, Biological psychiatry
The effects of d-amphetamine (0.5 mg/kg orally) on regional cerebral glucose utilization were measured with positron emission tomography (PET) in 17 schizophrenics (along with a placebo-control group of an additional six schizophrenic patients). The acute d-amphetamine challenge tended to decrease glucose utilization throughout much of the brain, with a regional effect that was statistically significant in the left temporal cortex. There was no apparent relationship between the effects of amphetamine-induced changes in regional cerebral metabolism and psychotic symptom exacerbation. An exploratory analysis suggested that features characteristic of Crow's type II syndrome were significant predictors of cerebral hyporesponsivity to stimulant challenge, however
— id: 8462, year: 1994, vol: 36, page: 317, stat: Journal Article,

Plasma homovanillic acid in neuroleptic responsive and nonresponsive schizophrenics
Duncan E; Wolkin A; Angrist B; Sanfilipo M; Wieland S; Cooper TB; Rotrosen J
1993 Oct 15;34(8):523-528, Biological psychiatry
Changes in plasma homovanillic acid (HVA) were investigated in neuroleptic responsive and nonresponsive schizophrenics in order to delineate parameters of dopamine regulation, which may underlie differences in neuroleptic responsivity. Nineteen schizophrenics were treated with haloperidol for 6 weeks. HVA was sampled at baseline, 24 hr after initial neuroleptic dose, and after 6 weeks of treatment. Subjects were pretreated with debrisoquin in order to reduce the peripheral production of HVA. The responders had an initial rise in HVA at 24 hr after first neuroleptic dose, followed by a decline back to baseline over the 6 weeks of treatment. The nonresponders' HVA failed to rise at 24 hr after first neuroleptic dose. At 6 weeks of treatment their HVA had fallen to significantly below baseline. Thus, a rise in HVA 24 hr after the first dose of neuroleptic predicted treatment response; a fall in HVA at 6 weeks to below pretreatment values was associated with neuroleptic nonresponse
— id: 57549, year: 1993, vol: 34, page: 523, stat: Journal Article,

Elevated PLA2 activity in schizophrenics and other psychiatric patients
Noponen M; Sanfilipo M; Samanich K; Ryer H; Ko G; Angrist B; Wolkin A; Duncan E; Rotrosen J
1993 Nov 1;34(9):641-649, Biological psychiatry
We measured serum phospholipase A2 (PLA2) activity in 39 schizophrenics, 26 psychiatric controls, and 26 normal controls using a radioenzymatic assay with phosphatidylcholine as precursor. Serum PLA2 activity was significantly higher in schizophrenics (p = 0.002) and other psychiatric (including substance abusing) patients (p = 0.032) than in normal controls. Enzyme activity did not differ between the schizophrenic patients and psychiatric controls. Fifty-one percent of the schizophrenics and 46% of psychiatric controls had PLA2 values above the highest value for normal controls. In the psychiatric control group higher than normal PLA2 activities were observed in all diagnostic categories, including major depression, bipolar disorder, posttraumatic stress disorder (PTSD), and substance abuse. In the context of others' findings of increased circulating PLA2 in infectious and inflammatory conditions, these increases must be viewed as disease nonspecific. The significance of these changes and their relationship to other acute-phase protein changes needs to be clarified in future research
— id: 23585, year: 1993, vol: 34, page: 641, stat: Journal Article,

ACUTE CEREBRAL METABOLIC RESPONSE TO HALOPERIDOL - BIOCHEMICAL AND BEHAVIORAL CORRELATIONS
SIMKOWITZ, P; BARTLETT, EJ; BRODIE, JD; CONVIT, A; WOLKIN, A; FRIEDHOFF, AJ; DEWEY, SL; WOLF, AP
1993 MAR 15 ;33(6A):A68-A68, Biological psychiatry
— id: 54173, year: 1993, vol: 33, page: A68, stat: Journal Article,

Negative symptoms and hypofrontality in chronic schizophrenia
Wolkin A; Sanfilipo M; Wolf AP; Angrist B; Brodie JD; Rotrosen J
1992 Dec;49(12):959-965, Archives of general psychiatry
Frontal lobe dysfunction is widely suspected to underlie negative symptoms of schizophrenia. This hypothesis is based largely on long-standing observations of the similarities between the effects of frontal lobe lesions and negative symptoms. However, there is little direct evidence specifically for such an association in schizophrenic patients. We measured the relationship between decreased relative prefrontal cortex glucose metabolism (hypofrontality) using positron emission tomography and evaluated the severity of negative symptoms in 20 chronic schizophrenics who underwent scanning while not receiving neuroleptic drugs. We found a close relationship between negative symptoms and prefrontal hypometabolism, particularly in the right dorsolateral convexity. This association was regionally specific. Furthermore, there was no evidence that this relationship was an artifact of age, cerebral atrophy, or severity of positive symptoms
— id: 57503, year: 1992, vol: 49, page: 959, stat: Journal Article,

Amphetamine response and duration of illness in schizophrenia
Angrist, B; Sanfilipo, M; Wolkin, A
1991 Oct;5(3):200-201, Biological psychiatry
— id: 106690, year: 1991, vol: 5, page: 200, stat: Journal Article,

Stability of resting deoxyglucose metabolic values in PET studies of schizophrenia
Bartlett EJ; Barouche F; Brodie JD; Wolkin A; Angrist B; Rotrosen J; Wolf AP
1991 May;40(1):11-20, Psychiatry research
Positron emission tomography (PET) and the deoxyglucose method were used to determine the test-retest stability of regional cerebral glucose metabolism in 8 male schizophrenic patients and 11 normal control subjects, scanned twice under baseline (resting) conditions. Normal and schizophrenic subjects showed comparable stability of regional metabolism. When the regional values were scaled to compensate for the effects of changes in whole brain metabolism, the resulting mean regional changes were reduced to about 1-2% in both groups. This study demonstrates that the baseline resting state is an appropriate reference state for schizophrenic subjects in deoxyglucose PET experiments
— id: 14038, year: 1991, vol: 40, page: 11, stat: Journal Article,

Importance of pharmacologic control in PET studies: effects of thiothixene and haloperidol on cerebral glucose utilization in chronic schizophrenia
Bartlett EJ; Wolkin A; Brodie JD; Laska EM; Wolf AP; Sanfilipo M
1991 Oct;40(2):115-124, Psychiatry research
This study compares the effects of two neuroleptic drugs with different pharmacologic characteristics (thiothixene and haloperidol) on cerebral glucose utilization in chronic schizophrenic inpatients. Positron emission tomographic (PET) scans were obtained from all subjects in a neuroleptic-free condition and again after 4-6 weeks of neuroleptic treatment. Eight subjects were treated with thiothixene and 12 with haloperidol. Thiothixene and haloperidol had different metabolic effects. For example, all thiothixene-treated subjects showed increased whole brain glucose utilization; all but one haloperidol-treated subject showed decreased utilization. Different patterns of relative prefrontal and striatal metabolism were also observed. These results highlight the importance of controlling for the effects of neuroleptic treatment and indicate the difficulty of interpreting data from studies with complex or poorly defined drug regimens
— id: 13887, year: 1991, vol: 40, page: 115, stat: Journal Article,

Dopamine blockade and clinical response: evidence for two biological subgroups of schizophrenia
Wolkin A; Barouche F; Wolf AP; Rotrosen J; Fowler JS; Shiue CY; Cooper TB; Brodie JD
1989 Jul;146(7):905-908, American journal of psychiatry
Because CNS neuroleptic concentration cannot be directly measured in patients, the relation between clinical response and extent of dopamine receptor blockade is unknown. This relationship is critical in ascertaining whether nonresponse to neuroleptics is the result merely of inadequate CNS drug levels or of more basic biological differences in pathophysiology. Using [18F]N-methylspiroperidol and positron emission tomography, the authors assessed dopamine receptor occupancy in 10 schizophrenic patients before and after treatment with haloperidol. Responders and nonresponders had virtually identical indices of [18F]N-methylspiroperidol uptake after treatment, indicating that failure to respond clinically was not a function of neuroleptic uptake or binding in the CNS
— id: 8395, year: 1989, vol: 146, page: 905, stat: Journal Article,

Dopamine receptor occupancy and plasma haloperidol levels
Wolkin A; Brodie JD; Barouche F; Rotrosen J; Wolf AP; Smith M; Fowler J; Cooper TB
1989 May;46(5):482-484, Archives of general psychiatry
— id: 23596, year: 1989, vol: 46, page: 482, stat: Journal Article,

Regional glucose metabolism in chronic schizophrenia
Brodie JD; Wolkin A; Wolf AP; Volkow N; Russell JA; Van Gelder P; Jaeger J; Fowler J; Rotrosen J; Cancro R
1988 ;3(1):54-54, American journal of physiologic imaging
— id: 11210, year: 1988, vol: 3, page: 54, stat: Journal Article,

Serial [18F]N-methylspiroperidol PET studies to measure changes in antipsychotic drug D-2 receptor occupancy in schizophrenic patients
Smith M; Wolf AP; Brodie JD; Arnett CD; Barouche F; Shiue CY; Fowler JS; Russell JA; MacGregor RR; Wolkin A; et al.
1988 Apr 1;23(7):653-663, Biological psychiatry
An indirect approach to the relationship among drug dose, plasma level, and the competition between a labeled neuroleptic drug [18F]N-methylspiroperidol (18F-NMS) for binding sites in striatal tissue in normal and schizophrenic subjects is described. The slope of the line plotting the ratio of activity in the striatum (As) to activity in the cerebellum (Ac) versus time up to 5 hr postinjection of 18F-NMS is taken as a marker of site occupancy. An inverse relation between labeled competitor uptake and drug plasma level has been demonstrated for the classes of antipsychotic drug studied. Striatal uptake studies showed a progressive increase in all subjects following drug withdrawal up to 156 hr postwithdrawal. Uptake and clearance of 18F-NMS in cerebellar tissue was not appreciably affected by antipsychotic medication or drug withdrawal
— id: 62153, year: 1988, vol: 23, page: 653, stat: Journal Article,

Low frontal glucose utilization in chronic schizophrenia: a replication study
Wolkin A; Angrist B; Wolf A; Brodie JD; Wolkin B; Jaeger J; Cancro R; Rotrosen J
1988 Feb;145(2):251-253, American journal of psychiatry
Frontal/posterior ratios of cerebral glucose metabolism as determined by positron emission tomography were significantly lower in 13 chronic schizophrenic patients than in eight normal control subjects, as were absolute metabolic rates in both the frontal and posterior regions. The differences were not accounted for by cerebral atrophy
— id: 11197, year: 1988, vol: 145, page: 251, stat: Journal Article,

PET STUDIES IN SCHIZOPHRENIA
Brodie, JD; Wolf, AP; Bartlett, E; Wolkin, A; Vangelder, P; Volkow, N
1987 Apr;32(1-2):788-788, International journal of neuroscience
— id: 31395, year: 1987, vol: 32, page: 788, stat: Journal Article,

PET STUDIES IN SCHIZOPHRENIA
Brodie, JD; Wolf, AP; Wolkin, A; Arnett, CD; Angrist, B; Fowler, J; Smith, M; Russell, J; Logan, J; Christman, D; Rotrosen, J; Volkow, N
1987 Apr;32(1-2):445-445, International journal of neuroscience
— id: 31391, year: 1987, vol: 32, page: 445, stat: Journal Article,

Effects of amphetamine on local cerebral metabolism in normal and schizophrenic subjects as determined by positron emission tomography
Wolkin A; Angrist B; Wolf A; Brodie J; Wolkin B; Jaeger J; Cancro R; Rotrosen J
1987 ;92(2):241-246, Psychopharmacology
The effects of d-amphetamine (0.5 mg/kg PO) on regional cerebral glucose utilization were measured with Positron Emission Tomography (PET). Subjects included ten chronic schizophrenics and six controls who received amphetamine, and six chronic schizophrenics and nine controls who received placebo or no treatment. Amphetamine decreased glucose metabolism in all regions studied (frontal, temporal, and striatal) in normal and schizophrenic subjects. The metabolic effects of amphetamine were correlated with plasma level of the drug. Cortical atrophy was associated with a blunted metabolic response
— id: 23614, year: 1987, vol: 92, page: 241, stat: Journal Article,

Essential fatty acid supplementation during early alcohol abstinence
Wolkin A; Segarnick D; Sierkierski J; Manku M; Horrobin D; Rotrosen J
1987 Feb;11(1):87-92, Alcoholism: clinical & experimental research
Interactions between ethanol, prostaglandins, and essential fatty acids (EFA) have led to the hypothesis that acute alcohol withdrawal and the sequelae of chronic alcoholism may be related to an EFA/prostaglandin deficiency. To test this hypothesis, EFA profiles in blood-lipid fractions, serum liver enzymes, cognitive function, and alcohol craving were measured in 27 acutely abstinent alcoholics before and after a 3-week double-blind trial of EFA supplementation. Upon entry into the study, alcoholics had significant differences in EFA levels as compared to normal controls, and serum levels of liver enzymes tended to correlate with these EFA levels. After 21 days, cognitive function, alcohol craving, and liver enzymes all improved in both the EFA and placebo groups; most EFA levels also approached normal values. There were no treatment effects of EFA supplementation at the dose used
— id: 23610, year: 1987, vol: 11, page: 87, stat: Journal Article,

MADNESS AND CLARITY
WOLKIN, A; CANCRO, R
1987 JUN ;10(2):225-226, Behavioral & brain sciences
— id: 41669, year: 1987, vol: 10, page: 225, stat: Journal Article,

EFFECTS OF AMPHETAMINE ON LOCAL CEREBRAL METABOLISM IN NORMAL AND SCHIZOPHRENIC SUBJECTS AS DETERMINED BY POSITRON EMISSION TOMOGRAPHY USING [C-11-1] 2-DEOXY-D-GLUCOSE (C-11-2DG)
BRODIE, JD; WOLKIN, A; ANGRIST, B; WOLF, AP; JORDAN, B; JAEGER, J; CANCRO, R; ROTROSEN, J
1986 JUN ;27(6):901-901, Journal of nuclear medicine
— id: 41433, year: 1986, vol: 27, page: 901, stat: Journal Article,

Niacin-induced flush as a measure of prostaglandin activity in alcoholics and schizophrenics
Fiedler P; Wolkin A; Rotrosen J
1986 Nov;21(13):1347-1350, Biological psychiatry
— id: 23617, year: 1986, vol: 21, page: 1347, stat: Journal Article,

The dexamethasone suppression test and response to placebo
Peselow ED; Lautin A; Wolkin A; Rohrs C; Novatt A; Siekierski J; Rotrosen J
1986 Oct;6(5):286-291, Journal of clinical psychopharmacology
The predictive value of the dexamethasone suppression test (DST) was evaluated in two consecutive double-blind, placebo-controlled trials evaluating 61 depressed inpatients randomized to either one of two drugs, sertraline or oxaprotiline, or placebo over a 4-week clinical trial. For 30 patients who completed at least 3 weeks of double-blind treatment on either drug, the initial DST was not predictive of response to drug treatment. For the 17 patients who completed at least 3 weeks of double-blind treatment on placebo, the presence of a positive DST predicted a statistically significantly poorer response to placebo as opposed to a negative DST. These preliminary findings suggest that for depressed individuals who present with a positive DST, remission without active medication is less likely and somatic treatment should be considered
— id: 23618, year: 1986, vol: 6, page: 286, stat: Journal Article,

SERIAL [F-18] N-METHYLSPIROPERIDOL (F-18 NMS) PET STUDIES MEASURE CHANGES IN ANTIPSYCHOTIC DRUG D2 RECEPTOR OCCUPANCY IN SCHIZOPHRENICS
SMITH, M; WOLF, AP; SHIUE, CY; FOWLER, JS; RUSSELL, JAG; MACGREGOR, R; ARNETT, C; LOGAN, J; WOLKIN, A; ROTROSEN, J; BRODIE, JD
1986 JUN ;27(6):880-880, Journal of nuclear medicine
— id: 41431, year: 1986, vol: 27, page: 880, stat: Journal Article,

Essential fatty acid supplementation in tardive dyskinesia
Wolkin A; Jordan B; Peselow E; Rubinstein M; Rotrosen J
1986 Jul;143(7):912-914, American journal of psychiatry
Preclinical and clinical observations suggest that enhancement of prostaglandin activity inhibits catecholamine release and may have antidyskinetic effects. A double-blind therapeutic trial with prostaglandin precursor essential fatty acids was conducted in 16 patients with tardive dyskinesia. No beneficial effects were seen
— id: 23619, year: 1986, vol: 143, page: 912, stat: Journal Article,

Amphetamine response and relapse risk after depot neuroleptic discontinuation
Angrist B; Peselow E; Rubinstein M; Wolkin A; Rotrosen J
1985 ;85(3):277-283, Psychopharmacology
Twenty-five schizophrenic outpatient subjects in a depot neuroleptic discontinuation study received an amphetamine challenge approximately 6 weeks after their last dose. Only five of these showed greater than three-point increases in positive symptoms on the BPRS, and all five relapsed within 30 days of the challenge. The 20 with less than three-point increases in positive symptoms showed extremely variable stability, relapsing from 20- greater than 600 days after the challenge. Thus, increase in positive symptoms after amphetamine may identify a group at risk for rapid relapse after neuroleptic discontinuation, but lack of such a response gives little prognostic information
— id: 23630, year: 1985, vol: 85, page: 277, stat: Journal Article,

Persistence of cerebral metabolic abnormalities in chronic schizophrenia as determined by positron emission tomography
Wolkin A; Jaeger J; Brodie JD; Wolf AP; Fowler J; Rotrosen J; Gomez-Mont F; Cancro R
1985 May;142(5):564-571, American journal of psychiatry
Local cerebral metabolic rates were determined by positron emission tomography and the deoxyglucose method in a group of 10 chronic schizophrenic subjects before and after somatic treatment and in eight normal subjects. Before treatment, schizophrenic subjects had markedly lower absolute metabolic activity than did normal controls in both frontal and temporal regions and a trend toward relative hyperactivity in the basal ganglia area. After treatment, their metabolic rates approached those seen in normal subjects in nearly all regions except frontal. Persistence of diminished frontal metabolism was manifested as significant relative hypofrontality. These findings suggest specific loci of aberrant cerebral functioning in chronic schizophrenia and the utility of positron emission tomography in characterizing these abnormalities
— id: 23625, year: 1985, vol: 142, page: 564, stat: Journal Article,

REGIONAL GLUCOSE-METABOLISM IN CHRONIC-SCHIZOPHRENIA
Brodie, JD; Wolkin, A; Wolfe, AP; Jaeger, J; Fowler, J; Rotrosen, J; Cancro, R
1984 ;2(3):226-226, International journal of psychophysiology
— id: 30978, year: 1984, vol: 2, page: 226, stat: Journal Article,

TRH test abnormalities in psychiatric disorders
Wolkin A; Peselow ED; Smith M; Lautin A; Kahn I; Rotrosen J
1984 Jun;6(3-4):273-281, Journal of affective disorders
Blunted responses to thyrotropin-releasing hormone (TRH) stimulation have been found consistently in depressed patients, and have been reported in other affective disorders as well. In a smaller number of schizophrenic subjects, TRH tests have generally been normal. Thus, it has been suggested that this test may have diagnostic utility in distinguishing schizophrenia from affective disorders. In the present study the TRH test was performed upon a sample of 51 subjects that included 17 schizophrenics in order to further study the diagnostic or symptom specificity of this endocrine test. Abnormal TRH tests were present in both schizophrenic and affectively disturbed patients. There were no correlations with ratings of depression or other aspects of psychopathology. Factors which may have previously obscured abnormal TRH tests in schizophrenia are discussed
— id: 23634, year: 1984, vol: 6, page: 273, stat: Journal Article,

Plasma cortisol values after dexamethasone in depressed inpatients
Peselow ED; Serby M; Wolkin A; Deutsch SI; Fricchione G; Rotrosen JP
1983 Feb;3(1):45-46, Journal of clinical psychopharmacology
— id: 23572, year: 1983, vol: 3, page: 45, stat: Journal Article,

Red cell phospholipids in schizophrenia
Lautin A; Cordasco DM; Segarnick DJ; Wood L; Mason MF; Wolkin A; Rotrosen J
1982 Dec 27;31(26):3051-3056, Life sciences
Phospholipids in red blood cells (RBCs) of schizophrenics and controls were determined. Three different RBC preparations and two different extraction methods were used. Phospholipids were separated by thin layer chromatography and by high pressure liquid chromatography, and were quantified by phosphorus analysis and by ultraviolet absorption. Findings were consistent with values previously reported for normals. However, in contrast to recent reports of elevated phosphatidylserine levels in schizophrenics' RBCs, we observed no differences between populations
— id: 23640, year: 1982, vol: 31, page: 3051, stat: Journal Article,