mortem studies (Am J Psychiatry 1999;156:72–78). Since in this study regions of interest were used, 5-HT 2A R changes may have been missed in some brain areas. Therefore, data were analyzed further using Statistical Parametric Mapping (SPM), which compares all voxels of the brain. We also used this method to examine the relationship between 5-HT 2A R binding potential (BP) and 5 PANSS-derived factors: negative, positive, activation, dysphoric and autistic preoccupation (Psychopathol- ogy 1997;30:263–274). Twelve antipsychotic-free schizophrenic patients (10M, 2F; age 30  6 y) and 24 age-matched controls (10M, 14F; age 29  6 y) were scanned. The 5-HT 2A R BP was estimated for each voxel by the ratio to the cerebellum between 65 and 90 min after [ 18 F]setoperone bolus injection. The resulting parametric 5-HT 2A R BP images were spatially normalized using a ligand specific template (NeuroImage 1999;9:545– 553). Analyses of covariance were done by SPM96 with age as covariate of no interest and applying no global normalization. Corrected p values 0.05 at cluster or voxel level were considered significant. The patients and controls were compared using a 1-subject-2-conditions paradigm. Correlations between 5-HT 2A R BP and the 5 factors were tested for patients only using a 1-subject-1-covariate-of-interest paradigm. No significant differences were detected between patients and controls and no significant correlations were observed between 5-HT 2A R BP and any of the 5 factors. Thus, SPM analysis confirmed the lack of substantial 5-HT 2A R BP differences between schizophrenic patients and controls. 162. EXPLORING ORBITOFRONTAL DYSFUNCTION IN SCHIZOPHRENIA: A NEUROPSYCHOLOGICAL ASSAY B.D. Shurman, K.H. Nuechterlein UCLA Department of Psychiatry and Biobehavioral Sciences, Los Angeles, CA 90095-6968 Research on the role of frontal lobe dysfunction in schizophrenia has predominantly focused on the dorsolateral prefrontal cortex. We are now using a decision-making task developed by Bechara and colleagues to examine whether another area of the prefrontal cortex, the orbitofrontal region, is disrupted in schizophrenia. The task involves selecting cards from four decks that provide different chances of reward and penalty. Normal subjects learn to select preferentially from the “winning” decks (those that provide the most advantageous reward/penalty ratio over time), but subjects with orbitofrontal damage do not. Neurological damage to other areas of the brain, including the dorsolateral prefrontal cortex, does not lead to abnormal performance on this task. We conducted a study comparing the performance of 40 subjects with DSM-IV schizophrenia and 10 normal subjects on this decision-making task. Schizophrenic subjects received clinical ratings using the BPRS, SANS, and SAPS and performed the decision-making task, a computerized version of the Wisconsin Card Sorting Test (WCST), and a Delayed Matching to Sample task (DMTS). The WCST and DMTS tasks were used as indices of dorsolateral prefrontal dysfunction. Our results indicate that schizophrenic subjects make significantly more disadvanta- geous decisions (choosing cards from disadvantageous decks) than do normal subjects. Negative symptoms are correlated with a pattern of disadvantageous decisions on this task. Performance on the WCST and DMTS did not correlate with performance on the decision making task. Our results support the possibility of orbitofrontal dysfunction in schizophrenia and suggest a link to negative symptoms. 163. THIRD VENTRICLE ENLARGEMENT AND DEVELOPMENTAL DELAY IN FIRST EPISODE SCHIZOPHRENIA D. Fannon, L. Tennakoon, V. Doku, S. O’Ceallaigh, X. Chitnis, A. Sumich, T. Sharma Section of Cognitive Psychopharmacology, Department of Psychiatry, De Crespigny Park, Denmark Hill, London SE5 8AF Enlargement of the lateral ventricles provides the most consistent evidence of structural brain abnormality in schizophrenia. The third ventricle has been studied to a lesser extent. The causes, effects, timing and course of ventricular pathology remain unclear. Establishing the processes underlying ventricular enlargement in schizophrenia will contribute to unraveling it’s aetiology. Detailed information on childhood development was collected from the mothers of 21 patients experiencing their first episode of schizophrenia, schizoaffective disorder or schizo- phreniform psychosis. T1-weighted images were obtained in 1.5 mm contiguous sections for the whole brain in the axial plane. Volumes were calculated for ventricular CSF, whole brain, prefrontal, premotor, senso- rimotor, occipitoparietal regions including grey matter. There was a significant correlation between third ventricle volume and developmental score (r = 0.709, p  0.0001). 7 patients with developmental delay had significantly larger third and lateral ventricles than the 14 without. The groups were comparable for age, gender, height, handedness, education and socio-economic status. There were no other differences in whole brain volume adjusted measures between the groups. Patients with first episode schizophrenia with a history of developmental delay have larger ventricles. The presence of developmental delay may discriminate between ventricular pathology and other structural abnormality in schizo- phrenia. These findings are in keeping with a developmental model of schizophrenia. Financial support: Psychmed Ltd and Grosvenor House Group Estates. 164. ATTENUATED FRONTAL ACTIVATION DURING MENTAL ROTATION IN SCHIZOPHRENIA S. Swain, T.A. Russell, C.M. Andrew, W. Soni, R.G. Morris, E.T. Bullmore, S.C.R. Williams, T. Sharma Section of Cognitive Psychopharmacology, Department of Psychiatry, De Crespigny Park, Denmark Hill, London SE5 8AF Patients with schizophrenia are impaired on tasks of occulomotor and haptic delay as well as visuo-spatial working memory, suggestive of frontal cortex abnormalities. Mental rotation tasks combine elements of visuo-spatial processing and working memory which requires the involvement of the central executive, localized to the frontal cortex. We used fMRI to investi- gate a mental rotation task in 5 dextral schizophrenic patients and 7 controls matched on age, IQ and handedness. We hypothesised that patients would have a deficit in mental rotation which will manifest as abnormalities in the BOLD signal in the frontal cortex. Schizophrenic subjects have intact basic spatial processing, therefore we predicted that occipital areas will be equally active in both groups while frontal regions of activation will be reduced or absent in the schizophrenic group. No significant differences were found between the two groups on accuracy or reaction time. Control subjects showed activation in bilateral visual cortical areas and frontal cortices. As predicted schizophrenic patients elicited activation in occipital areas but no activation in frontal Thursday Abstracts 49S BIOL PSYCHIATRY 2000;47:1S–173S