- Email: [email protected]
150. Talairach altas-based volumetric analysis of the brain in schizophrenia
Thursday Abstracts
148. ALTERED GENE EXPRESSION OF DOPAMINERGIC MARKERS IN THE MIDBRAIN OF SCHIZOPHRENIC PATIENTS C. Keczkemethy, M. Akil, S.M. Colvin, T.M. Hyde, J.E. Kleinman
BIOL PSYCHIATRY 2000;47:1S–173S
45S
aggression (F(1, 110) ⫽ 4.10, p ⫽ .045, R2 ⫽ .036). Even with a wide range of clinical indicators, aggressive behavior in schizophrenia remains very difficult to predict. Although clinically rated impulse control deficit was more common in the hospitalized patients, the two groups did not differ on rate of overt aggression. Thus, non-aggressive episodes of impulsive behavior may be qualitatively different from aggressiveness, yet still a barrier to discharge.
Clinical Brain Disorders Branch, National Institute of Mental Health/ IRP, NIH, Bethesda, MD, 20892 Dopamine has long been implicated in the pathophysiology of schizophrenia. Recent postmortem studies demonstrate a reduction in the density of axons immunoreactive for the dopamine transporter (DAT) or tyrosine hydroxylase (TH) in the prefrontal and entorhinal cortices of schizophrenic patients (Akil et al 1999, Akil et al in press). We hypothesized that these changes reflect alterations in the gene expression of DAT and TH in mesencephalic DA neurons. We used in situ hybridization to compare the levels of DAT and TH mRNA in postmortem tissue specimens from the midbrains of schizophrenic subjects (n ⫽ 12) and normal controls (n ⫽ 12). The groups were matched in a pairwise fashion on the basis of age, race, sex, and postmortem interval. Cytoarchitectonic criteria and TH immunocytochemistry were used to identify 5 dopaminergic cell groups in each subject: the substantia nigra pars lateralis (SNPL), the dorsal and ventral tiers of the pars compacta (DTSN and VTSN respectively), the paranigral nucleus (PN) and the ventral tegmental area (VTA). Quantitative analyses revealed a marked decrease in DAT mRNA levels in a subset of schizophrenic subjects relative to matched controls. Overall group means of DAT mRNA levels were decreased in the schizophrenic group in all nuclei examined. However, this decrease reached statistical significance only in the SNPL (49%, p ⫽ 0.04). Preliminary analysis of TH mRNA expression revealed a pattern of reduction in schizophrenic subjects similar to that found with DAT mRNA. These finding implicate mesencephalic dopaminergic neurons as potential sites of dysfunction in schizophrenia.
149. VERBAL AND PHYSICAL AGGRESSION IN POOR OUTCOME, GERIATRIC SCHIZOPHRENIA C.R. Bowie (1,2), P.J. Moriarty (1), P.D. Harvey (3), M. Parrella (2), L. White (2), K.L. Davis (3) (1) Department of Psychology, Hofstra University; (2) Pilgrim Psychiatric Center; (3) Department of Psychiatry, Mt. Sinai School of Medicine Aggression is prevalent in both schizophrenia and dementing conditions. Elderly persons with schizophrenia display an above average level of verbal and physical aggression. This study examined the role of cognitive functioning, adaptive functioning, and symptomatology in predicting aggression in geriatric schizophrenic patients. Subjects resided in either a state institution or a nursing home. They were assessed with a comprehensive neuropsychological assessment battery, and rated with the Positive and Negative Syndrome Scale, Social Adaptive Functions Scale, and Overt Aggression Scale. Subjects who resided in a nursing home were older, more cognitively impaired, and more functionally impaired than their institutionalized counterparts. The prevalence of aggressiveness in the past week in this geriatric sample of schizophrenic patients (37%) was similar to previous studies examining aggressiveness in acutely hospitalized younger patients. Negative symptom severity was predictive of physical aggression in the hospitalized group (F(1, 54) ⫽ 8.83, p ⫽ .004, R2 ⫽ .141). In the nursing home group, positive symptom severity was predictive of verbal aggression (F(1, 110) ⫽ 11.02, p ⫽ .001, R2 ⫽ .091) and self-care ability was predictive of physical
150. TALAIRACH ALTAS-BASED VOLUMETRIC ANALYSIS OF THE BRAIN IN SCHIZOPHRENIA C. Johnson (1), V. Cardenas-Nicolson (2,4), Y. Eliaz (1), L. Chosiad (1), R.F. Deicken (1,2,3) (1) Mental Health Service, and (2) Magnetic Resonance Unit, San Francisco Department of Veteran Affairs Medical Center and the Department of (3) Psychiatry, University of California, San Francisco Recent studies have suggested that volumetric abnormalities in schizophrenic brains may be multi-regional. In this study, Talairach atlas-based volumetric analysis was used to measure structurally homogeneous regions of interest in schizophrenic brains. Specifically, 7 different regions were chosen and specified as: 1.) Dorsolateral (Brodmann areas 9,10,46), 2.) Orbitofrontal (Brodmann areas 10,11,47), Inferior Frontal (Brodmann areas 44,45), 4.) Anterior Cingulate Cortex (Brodmann area 24), 5.) Retrosplenial cortex (Brodmann areas 29,30), 6.) Entorhinal Cortex or Parahippocampal Gyrus (Brodmann area 28), and 7.) Superior Temporal Gyrus (Brodmann area 22). We hypothesized that schizophrenics would have significantly smaller volumes in these cortical regions when compared with healthy controls. Fifteen patients (mean age 38.4, 12M/3F) meeting DSM-IV criteria for schizophrenia were compared to 14 control subjects (mean age 34, 12M/2F). Grey and white matter volumes for each region of interest were obtained using in-house software. T-test analysis showed a significant decrease in the cortical grey matter volumes of schizophrenics in the anterior cingulate (p ⫽ .006), dorsolateral (p ⫽ .042), inferior frontal (p ⫽ .019), orbitofrontal (p ⫽ .047), and retrosplenial (p ⫽ .041) regions. There was a reduction trend observed in the superior temporal region (p ⫽ .088), but no significant reduction of the cortical grey matter volume in the entorhinal region. The white matter volumes were also assessed, but there were no significant differences between patients and controls. These findings suggest that there is a reduction of the grey matter volume in several cortical regions in schizophrenic brains, but that this deficit is not distributed uniformly throughout the cortex. Therefore, these findings also suggest the importance of looking at discrete regions of the cortex that are structurally homogeneous.
151. RIGHT ANTERIOR CINGULATE METABOLIC ABNORMALITY IN CHRONIC PARANOID SCHIZOPHRENIA T.E. Nordahl, C. Carter, L. Kraft, J. Baldo, S. Salamat, R. Salo, N. Kusubov UC Davis/Napa State Research Center, 2100 Napa-Vallejo Highway, Napa, Calif. 94557 and Lawrence Berkeley National Laboratory, MS 55-121, 1 Cyclotron Rd., Berkeley, Calif. 94720 This study involves a PET-FDG study of 10 unmedicated outpatients with paranoid schizophrenia and 10 normal controls who were studied during performance of a 20 minute trial-by-trial computerized Stroop task during the uptake of the radio-tracer, FDG. The anterior cingulate
148. ALTERED GENE EXPRESSION OF DOPAMINERGIC MARKERS IN THE MIDBRAIN OF SCHIZOPHRENIC PATIENTS C. Keczkemethy, M. Akil, S.M. Colvin, T.M. Hyde, J.E. Kleinman
BIOL PSYCHIATRY 2000;47:1S–173S
45S
aggression (F(1, 110) ⫽ 4.10, p ⫽ .045, R2 ⫽ .036). Even with a wide range of clinical indicators, aggressive behavior in schizophrenia remains very difficult to predict. Although clinically rated impulse control deficit was more common in the hospitalized patients, the two groups did not differ on rate of overt aggression. Thus, non-aggressive episodes of impulsive behavior may be qualitatively different from aggressiveness, yet still a barrier to discharge.
Clinical Brain Disorders Branch, National Institute of Mental Health/ IRP, NIH, Bethesda, MD, 20892 Dopamine has long been implicated in the pathophysiology of schizophrenia. Recent postmortem studies demonstrate a reduction in the density of axons immunoreactive for the dopamine transporter (DAT) or tyrosine hydroxylase (TH) in the prefrontal and entorhinal cortices of schizophrenic patients (Akil et al 1999, Akil et al in press). We hypothesized that these changes reflect alterations in the gene expression of DAT and TH in mesencephalic DA neurons. We used in situ hybridization to compare the levels of DAT and TH mRNA in postmortem tissue specimens from the midbrains of schizophrenic subjects (n ⫽ 12) and normal controls (n ⫽ 12). The groups were matched in a pairwise fashion on the basis of age, race, sex, and postmortem interval. Cytoarchitectonic criteria and TH immunocytochemistry were used to identify 5 dopaminergic cell groups in each subject: the substantia nigra pars lateralis (SNPL), the dorsal and ventral tiers of the pars compacta (DTSN and VTSN respectively), the paranigral nucleus (PN) and the ventral tegmental area (VTA). Quantitative analyses revealed a marked decrease in DAT mRNA levels in a subset of schizophrenic subjects relative to matched controls. Overall group means of DAT mRNA levels were decreased in the schizophrenic group in all nuclei examined. However, this decrease reached statistical significance only in the SNPL (49%, p ⫽ 0.04). Preliminary analysis of TH mRNA expression revealed a pattern of reduction in schizophrenic subjects similar to that found with DAT mRNA. These finding implicate mesencephalic dopaminergic neurons as potential sites of dysfunction in schizophrenia.
149. VERBAL AND PHYSICAL AGGRESSION IN POOR OUTCOME, GERIATRIC SCHIZOPHRENIA C.R. Bowie (1,2), P.J. Moriarty (1), P.D. Harvey (3), M. Parrella (2), L. White (2), K.L. Davis (3) (1) Department of Psychology, Hofstra University; (2) Pilgrim Psychiatric Center; (3) Department of Psychiatry, Mt. Sinai School of Medicine Aggression is prevalent in both schizophrenia and dementing conditions. Elderly persons with schizophrenia display an above average level of verbal and physical aggression. This study examined the role of cognitive functioning, adaptive functioning, and symptomatology in predicting aggression in geriatric schizophrenic patients. Subjects resided in either a state institution or a nursing home. They were assessed with a comprehensive neuropsychological assessment battery, and rated with the Positive and Negative Syndrome Scale, Social Adaptive Functions Scale, and Overt Aggression Scale. Subjects who resided in a nursing home were older, more cognitively impaired, and more functionally impaired than their institutionalized counterparts. The prevalence of aggressiveness in the past week in this geriatric sample of schizophrenic patients (37%) was similar to previous studies examining aggressiveness in acutely hospitalized younger patients. Negative symptom severity was predictive of physical aggression in the hospitalized group (F(1, 54) ⫽ 8.83, p ⫽ .004, R2 ⫽ .141). In the nursing home group, positive symptom severity was predictive of verbal aggression (F(1, 110) ⫽ 11.02, p ⫽ .001, R2 ⫽ .091) and self-care ability was predictive of physical
150. TALAIRACH ALTAS-BASED VOLUMETRIC ANALYSIS OF THE BRAIN IN SCHIZOPHRENIA C. Johnson (1), V. Cardenas-Nicolson (2,4), Y. Eliaz (1), L. Chosiad (1), R.F. Deicken (1,2,3) (1) Mental Health Service, and (2) Magnetic Resonance Unit, San Francisco Department of Veteran Affairs Medical Center and the Department of (3) Psychiatry, University of California, San Francisco Recent studies have suggested that volumetric abnormalities in schizophrenic brains may be multi-regional. In this study, Talairach atlas-based volumetric analysis was used to measure structurally homogeneous regions of interest in schizophrenic brains. Specifically, 7 different regions were chosen and specified as: 1.) Dorsolateral (Brodmann areas 9,10,46), 2.) Orbitofrontal (Brodmann areas 10,11,47), Inferior Frontal (Brodmann areas 44,45), 4.) Anterior Cingulate Cortex (Brodmann area 24), 5.) Retrosplenial cortex (Brodmann areas 29,30), 6.) Entorhinal Cortex or Parahippocampal Gyrus (Brodmann area 28), and 7.) Superior Temporal Gyrus (Brodmann area 22). We hypothesized that schizophrenics would have significantly smaller volumes in these cortical regions when compared with healthy controls. Fifteen patients (mean age 38.4, 12M/3F) meeting DSM-IV criteria for schizophrenia were compared to 14 control subjects (mean age 34, 12M/2F). Grey and white matter volumes for each region of interest were obtained using in-house software. T-test analysis showed a significant decrease in the cortical grey matter volumes of schizophrenics in the anterior cingulate (p ⫽ .006), dorsolateral (p ⫽ .042), inferior frontal (p ⫽ .019), orbitofrontal (p ⫽ .047), and retrosplenial (p ⫽ .041) regions. There was a reduction trend observed in the superior temporal region (p ⫽ .088), but no significant reduction of the cortical grey matter volume in the entorhinal region. The white matter volumes were also assessed, but there were no significant differences between patients and controls. These findings suggest that there is a reduction of the grey matter volume in several cortical regions in schizophrenic brains, but that this deficit is not distributed uniformly throughout the cortex. Therefore, these findings also suggest the importance of looking at discrete regions of the cortex that are structurally homogeneous.
151. RIGHT ANTERIOR CINGULATE METABOLIC ABNORMALITY IN CHRONIC PARANOID SCHIZOPHRENIA T.E. Nordahl, C. Carter, L. Kraft, J. Baldo, S. Salamat, R. Salo, N. Kusubov UC Davis/Napa State Research Center, 2100 Napa-Vallejo Highway, Napa, Calif. 94557 and Lawrence Berkeley National Laboratory, MS 55-121, 1 Cyclotron Rd., Berkeley, Calif. 94720 This study involves a PET-FDG study of 10 unmedicated outpatients with paranoid schizophrenia and 10 normal controls who were studied during performance of a 20 minute trial-by-trial computerized Stroop task during the uptake of the radio-tracer, FDG. The anterior cingulate