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421. Symptoms associated with amygdaloid activity in schizophrenia
Saturday Abstracts
420. A COMPARISON OF NEUROPSYCHOLOGICAL PROFILES IN PATIENTS WITH SCHIZOPHRENIA AND BIPOLAR PSYCHOSES L.J. Seidman (1,2), W.S. Kremen (3), D. Koren (4), S.V. Faraone (1,2), J.M. Goldstein (1,2), M.T. Tsuang (1,2) (1) Harvard Institute of Psychiatric Epidemiology and Genetics; (2) Harvard Medical School, Boston, MA; (3) University of California at Davis, Sacramento, CA USA; (4) Haifa University, Haifa, Israel Evidence for generalized neuropsychological deficits in schizophrenia is substantial whereas evidence for the specificity of dysfunction is relatively sparse. To assess specificity, we compared neuropsychological function in patients with chronic schizophrenia (n ⫽ 87), patients with chronic psychotic bipolar disorder (n ⫽ 15) and normal controls (n ⫽ 94). An extensive neuropsychological battery was administered. Groups were not significantly different on age, ethnicity and expected intellectual ability (based on single word reading). Patients with schizophrenia and bipolar psychoses were also similar on age at onset, number of hospitalizations, and daily neuroleptic-equivalent dose. Using multivariate analyses of variance with sex and parental SES as covariates, schizophrenia patients were significantly worse than controls on 7 of 8 neuropsychological functions (all but verbal ability), and were significantly more impaired than bipolar patients on abstraction, perceptual-motor speed and vigilance. Bipolar patients were significantly impaired compared to controls on verbal memory. Results were not attenuated when we controlled for a measure of behavior during the testing session, or for IQ, which was significantly lower in patients with schizophrenia. Consistent with previous work, analyses indicated that the two psychiatric groups had similar profile patterns, but that patients with schizophrenia had a more severe impairment than patients with bipolar psychoses. This suggests that level, but not profile type is different between the groups. Further research is required to determine whether similar mechanisms underly the neurocognitive deficits in these disorders.
421. SYMPTOMS ASSOCIATED WITH AMYGDALOID ACTIVITY IN SCHIZOPHRENIA S.F. Taylor (1), I. Liberzon (1), R. Tandon (1), L.R. Decker (1), R.A. Koeppe (2) University of Michigan, (1) Department of Psychiatry; (2) Department of Internal Medicine/Division of Nuclear Medicine The amygdaloid complex is a group of nuclei in the anterior temporal lobe which scan the environment for salient stimuli, particularly of a threatening nature. Grace and colleagues have suggested that abnormal perceptions of threat, which characterize the positive symptoms of schizophrenia, may reflect aberrant activity in the amygdaloid complex. To test this prediction, we analyzed correlations of symptom ratings with functional neuroimaging data obtained during a water activation paradigm with [O-15]PET. We studied 14 medicated, schizophrenic subjects and 13 healthy control subjects while they viewed a blank screen; pictures with salient, non-aversive content; or aversive content. Clinical ratings of schizophrenic symptoms were conducted with the BPRS and SANS. Both groups also completed the Physical and Social Anhedonia scales. The healthy subjects activated right and left amygdaloid complexes in response to salient images, with both non-aversive and aversive content. The schizophrenic subjects exhibited significantly less activation in the amygdala, as previously reported. BPRS positive symptoms correlated with greater activity in the left amygdala, across all conditions (non-aversive condition: r ⫽ 0.71, df ⫽ 13, p ⫽ 0.04, corrected).
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Correlations with negative symptoms were not significant. However, in both groups, we noted correlations between greater physical anhedonia and lower amygdaloid activity, strongest in the right amygdala while viewing aversive pictures (r ⫽ ⫺0.59, df ⫽ 22, p ⫽ 0.03, corrected). These findings support the hypothesis that implicate aberrant activity of the amygdala in positive symptoms of schizophrenia. Associations with physical anhedonia also suggest a role for these structures in emotional experience in both groups, probably orthogonal to pathophysiology.
422. A LONGITUDINAL INVESTIGATION OF NEUROPSYCHOLOGICAL FUNCTIONING AND ITS RELATIONSHIP WITH SYMPTOMATOLOGY IN FIRSTEPISODE PSYCHOSIS T. Sharma, E.M. Riley, D. McGovern, S. Rabe-Hesketh, D.G. Fannon, V.C. Doku, S. O’Ceallaigh, W. Soni, M. Santamaria Section of Cognitive Psychopharmacology, Department of Psychiatry, De Crespigny Park, Denmark Hill, London SE5 8AF This study assessed the nature of neuropsychological functioning and its relationship to symptomatology over a period of six months. 41 patients experiencing their first episode of psychosis (according to DSM-IV criteria) completed a comprehensive battery of neuropsychological tests designed to assess executive function, verbal and non-verbal memory, working memory, attention, psychomotor speed and spatial ability at baseline, 3 months and six months. Symptom ratings, as measured by the PANSS, were collected at the same time points. Significant improvements in neuropsychological performance were observed in executive function, verbal memory and psychomotor speed. Improvements in executive function and verbal memory were found to be correlated with decreases in both positive and negative symptomatology over time. Psychomotor speed, however, was related to changes in the negative subscale only. Despite non-significant changes in working memory and spatial ability these domains were also found to be significantly correlated with improvements in negative symptomatology. Attention and non-verbal memory were not correlated with changes in the clinical state. These findings suggest that in the first six months of their illness, first-episode patients do not show any deterioration in neuropsychological functioning. It was also shown that performance in certain domains correlates with clinical state in the early phase of the illness. It would appear, however, that attention and non-verbal memory are independent of changes in symptomatology and may be seen as “trait” rather than “state” related functions. Financial support: Psychmed Ltd and Grosvenor House Group Estates.
423. 5-HT2 RECEPTOR ACTIVATION: A COMMON DENOMINATOR OF THE NMDA ANTAGONIST AND 5-HT2A AGONIST MODELS OF PSYCHOSIS? F.X. Vollenweider (1), D. Ba¨chle (1), K.L. Leenders (2), J. Missimer (2), D. Hell (1) (1) Psychiatric University Hospital, P.O. Box 88, CH-8028 Zu¨rich, Switzerland; (2) PET Center of the Paul Scherrer Institute (PSI), CH5232 Vijligen, Switzerland Both NMDA antagonists (S-ketamine) and 5-HT2A receptor agonists (psilocybin) produce symptoms in healthy humans resembling positive,
420. A COMPARISON OF NEUROPSYCHOLOGICAL PROFILES IN PATIENTS WITH SCHIZOPHRENIA AND BIPOLAR PSYCHOSES L.J. Seidman (1,2), W.S. Kremen (3), D. Koren (4), S.V. Faraone (1,2), J.M. Goldstein (1,2), M.T. Tsuang (1,2) (1) Harvard Institute of Psychiatric Epidemiology and Genetics; (2) Harvard Medical School, Boston, MA; (3) University of California at Davis, Sacramento, CA USA; (4) Haifa University, Haifa, Israel Evidence for generalized neuropsychological deficits in schizophrenia is substantial whereas evidence for the specificity of dysfunction is relatively sparse. To assess specificity, we compared neuropsychological function in patients with chronic schizophrenia (n ⫽ 87), patients with chronic psychotic bipolar disorder (n ⫽ 15) and normal controls (n ⫽ 94). An extensive neuropsychological battery was administered. Groups were not significantly different on age, ethnicity and expected intellectual ability (based on single word reading). Patients with schizophrenia and bipolar psychoses were also similar on age at onset, number of hospitalizations, and daily neuroleptic-equivalent dose. Using multivariate analyses of variance with sex and parental SES as covariates, schizophrenia patients were significantly worse than controls on 7 of 8 neuropsychological functions (all but verbal ability), and were significantly more impaired than bipolar patients on abstraction, perceptual-motor speed and vigilance. Bipolar patients were significantly impaired compared to controls on verbal memory. Results were not attenuated when we controlled for a measure of behavior during the testing session, or for IQ, which was significantly lower in patients with schizophrenia. Consistent with previous work, analyses indicated that the two psychiatric groups had similar profile patterns, but that patients with schizophrenia had a more severe impairment than patients with bipolar psychoses. This suggests that level, but not profile type is different between the groups. Further research is required to determine whether similar mechanisms underly the neurocognitive deficits in these disorders.
421. SYMPTOMS ASSOCIATED WITH AMYGDALOID ACTIVITY IN SCHIZOPHRENIA S.F. Taylor (1), I. Liberzon (1), R. Tandon (1), L.R. Decker (1), R.A. Koeppe (2) University of Michigan, (1) Department of Psychiatry; (2) Department of Internal Medicine/Division of Nuclear Medicine The amygdaloid complex is a group of nuclei in the anterior temporal lobe which scan the environment for salient stimuli, particularly of a threatening nature. Grace and colleagues have suggested that abnormal perceptions of threat, which characterize the positive symptoms of schizophrenia, may reflect aberrant activity in the amygdaloid complex. To test this prediction, we analyzed correlations of symptom ratings with functional neuroimaging data obtained during a water activation paradigm with [O-15]PET. We studied 14 medicated, schizophrenic subjects and 13 healthy control subjects while they viewed a blank screen; pictures with salient, non-aversive content; or aversive content. Clinical ratings of schizophrenic symptoms were conducted with the BPRS and SANS. Both groups also completed the Physical and Social Anhedonia scales. The healthy subjects activated right and left amygdaloid complexes in response to salient images, with both non-aversive and aversive content. The schizophrenic subjects exhibited significantly less activation in the amygdala, as previously reported. BPRS positive symptoms correlated with greater activity in the left amygdala, across all conditions (non-aversive condition: r ⫽ 0.71, df ⫽ 13, p ⫽ 0.04, corrected).
BIOL PSYCHIATRY 2000;47:1S–173S
129S
Correlations with negative symptoms were not significant. However, in both groups, we noted correlations between greater physical anhedonia and lower amygdaloid activity, strongest in the right amygdala while viewing aversive pictures (r ⫽ ⫺0.59, df ⫽ 22, p ⫽ 0.03, corrected). These findings support the hypothesis that implicate aberrant activity of the amygdala in positive symptoms of schizophrenia. Associations with physical anhedonia also suggest a role for these structures in emotional experience in both groups, probably orthogonal to pathophysiology.
422. A LONGITUDINAL INVESTIGATION OF NEUROPSYCHOLOGICAL FUNCTIONING AND ITS RELATIONSHIP WITH SYMPTOMATOLOGY IN FIRSTEPISODE PSYCHOSIS T. Sharma, E.M. Riley, D. McGovern, S. Rabe-Hesketh, D.G. Fannon, V.C. Doku, S. O’Ceallaigh, W. Soni, M. Santamaria Section of Cognitive Psychopharmacology, Department of Psychiatry, De Crespigny Park, Denmark Hill, London SE5 8AF This study assessed the nature of neuropsychological functioning and its relationship to symptomatology over a period of six months. 41 patients experiencing their first episode of psychosis (according to DSM-IV criteria) completed a comprehensive battery of neuropsychological tests designed to assess executive function, verbal and non-verbal memory, working memory, attention, psychomotor speed and spatial ability at baseline, 3 months and six months. Symptom ratings, as measured by the PANSS, were collected at the same time points. Significant improvements in neuropsychological performance were observed in executive function, verbal memory and psychomotor speed. Improvements in executive function and verbal memory were found to be correlated with decreases in both positive and negative symptomatology over time. Psychomotor speed, however, was related to changes in the negative subscale only. Despite non-significant changes in working memory and spatial ability these domains were also found to be significantly correlated with improvements in negative symptomatology. Attention and non-verbal memory were not correlated with changes in the clinical state. These findings suggest that in the first six months of their illness, first-episode patients do not show any deterioration in neuropsychological functioning. It was also shown that performance in certain domains correlates with clinical state in the early phase of the illness. It would appear, however, that attention and non-verbal memory are independent of changes in symptomatology and may be seen as “trait” rather than “state” related functions. Financial support: Psychmed Ltd and Grosvenor House Group Estates.
423. 5-HT2 RECEPTOR ACTIVATION: A COMMON DENOMINATOR OF THE NMDA ANTAGONIST AND 5-HT2A AGONIST MODELS OF PSYCHOSIS? F.X. Vollenweider (1), D. Ba¨chle (1), K.L. Leenders (2), J. Missimer (2), D. Hell (1) (1) Psychiatric University Hospital, P.O. Box 88, CH-8028 Zu¨rich, Switzerland; (2) PET Center of the Paul Scherrer Institute (PSI), CH5232 Vijligen, Switzerland Both NMDA antagonists (S-ketamine) and 5-HT2A receptor agonists (psilocybin) produce symptoms in healthy humans resembling positive,