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Motor performance in schizophrenia: Treatment effects and predictive validity
SATURDAZ MAY 20
tionships between duration and side effects of neuroleptic treatment and NSS. These findings suggest that neuroleptic treatment may only play a partial role in the development of NSS in patients with schizophrenia and NSS may be one of the biological markers of this disorder. To confirm the fmdings of this study, data on a prospective follow-up design of neuroleptic-naive patients after neuroleptic treatment will be presented.
249. AUTONOMIC REACTIVITY IN MANIC AND SCHIZOPHRENIC PATIENTS
D.B. Schnur, S. Smith, V. Marte, S. Mukherjee, H.A. Sackiem, A. Bernstein, & A. Smith Mt. Sinai School o f Medicine, N e w York, N Y 10029 We present findings from ongoing work aimed at examining differences in autonomic responsivity between schizophrenic and manic patients presented with attentionally valent stimuli. Neutral and attentionally significant tones were used to determine reactivity of the skin conductance response (SCR) and the fmger pulse amplitude response (FPAR) systems. Thirty-five schizophrenic and 24 manic patients were compared to 29 normals weekly for 4 weeks. In the first and last sessions, subjects were presented with a series of innocuous tones followed by an attentional task requiring a foot pedal response to tones of a given pitch. No stimuli were given during the second and third sessions. For FPAR, the schizophrenic and manic patients had significantly lower response frequencies to the attentional task than the control sample during both testing sessions (Kruskal-Wallis H _> 9.9; p _< 0.007), but patient groups were similar to each other. FPAR frequency to task significant stimuli were highly correlated across sessions (Spearman rho - 0.7; p = 0.0001). There were no between-group differences in SCR frequency to the attentional task or in SCR or FPAR frequency to the neutral tones. Responsivity to task relevant tones was always significantly greater than to neutral tones in both SCR and FPAR (Wilcoxon Z _> 5.2; p = 0.0001). Autonomic reactivity appears reduced in schizophrenic and manic patients when compared to controls, but there do not appear to be differences between patient groups. This relationship is temporally stable but only evident in FPAR when task-relevant tones are being used.
250. EXONIC AND INTRONIC POLYMORPHISMS IN THE DOPAMINE D3 GENE M.A. Crocq I, A. Mayerova 2, F. Duval l, A. Buguet -~, S. Bisser 4, & J.P. Macher I ~Centre Hospitalier, 6 8 2 5 0 R o u f f a c h , France; 2University of Freiburg, 79106 G e r m a n y ; 3CRSSA, 38702 La Tronche, France; 4University of L i m o g e s , France The dopamine D3 receptor is a major target fi)r antipsychotic drugs and forms one subfamily with the D2 and D& A few studies have shown a weak association between schizophrenia and homozygosity at a Bal l polymorphic site in the first exon of the D3 gene; however, this has not been replicated by others, and further studies are necessary. Using PCR we genotyped two di-allelic polymorphisms of the dopamine D3 gene, namely, the known Bal I site in the first exon and a recently localized Msp I site in the fourth intron, in Caucasians from France (n = 101) and Africans from the Republic of Congo (n = 56). At both loci, the predominant allele was different in Caucasians (Bal I allele 1: 0.67; Msp I allele 1: 0.52) and Africans (Bal 1 allele 1: 0.12; Msp I allele 1: 0.24). Within the African group, allelic frequencies did not differ between healthy subjects
BIOL PSYCHIATRY 1995:37:593-683
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and 25 patients with trypanosomiasis (sleeping sickness). Our results show that Bal I allelic frequencies in the D3 gene display ethnic variations, even though schizophrenia is present in all human cultures. This suggests that, if the Bal I locus is associated with schizophrenia, it might not be causative per se but instead be a marker which is linked to another causative mutation in some populations.
251. INCREASED IL-1 AND IL-3 LR IN SCHIZOPHRENIA P. Sirota 1,3, K. Schild 1,-~, A. Elizur 1,3, M. Djaldetti 2,3, & P. Fishman 2,3 nAbarbanel Mental Health Center, Bat Y a m , Israel; 2Golda Medical Center, Petach T i k v a h , Israel; 3Sackler Faculty o f Medicine, Tel Aviv University, Israel The interleukins play an important role in the development and maintenance of the immune system. Decreased cell-mediated immunity measures were found in schizophrenic patients. The purpose of the present study was to investigate the spontaneous production of interleukin 1 (IL3) and interleukin-3-1ike activity (IL-3-LA) by human mononuelear cells from schizophrenic patients compared to healthy individuals. IL-1 was significantly increased in schizophrenic patients as compared to controls. IL3-LA was slightly elevated in schizophrenic patients as compared to controls. These findings support the hypothesis of an autoimmune dysfunction in some schizophrenic patients.
252. MOTOR PERFORMANCE IN SCHIZOPHRENIA: TREATMENT EFFECTS AND PREDICTIVE VALIDITY J.A. Bates, R.M. Bilder, G. Reiter, A. Koreen, S.H. Geisler, B. Sheitman, M. Chakos, J. Alvir, & J.A. Lieberman Hillside H o s p i t a l - R e s e a r c h , Glen O a k s , N Y 11004 Recent studies have indicated that neuropsychological (NP) measures can be useful predictors of outcome in schizophrenia. Baseline motor performance appears as the most consistent predictive measure across studies; however, most studies so far have examined only baseline performance. The current study focused on motor tasks and their predictive value for determining outcome in schizophrenia. The study examined baseline measures and changes in performance over the first 8 weeks of neuroleptic treatment, to assess the relative contributions to the prediction of outcome. The literature also suggests that neuroleptics may have lateralized effects on motor functioning, and this study provides a unique opportunity to assess this question. The findings corroborate results of other studies in that baseline motor performance predicted outcome (R 2 = 0.21 ). There were significant decrements in motor performance over the first 8 weeks of neuroleptic treatment. There was a trend for treatment-related decrements in motor performance, but these change scores did not add significantly to predictive power based cm pretreatment scores alone. Finally, there were significant lateralized changes in motor performance. Tasks of fine motor coordination (peg placing) showed greater decline in left-sided performance, while simpler tasks of motor speed (finger tapping) showed greater decline in right-sided performance.
tionships between duration and side effects of neuroleptic treatment and NSS. These findings suggest that neuroleptic treatment may only play a partial role in the development of NSS in patients with schizophrenia and NSS may be one of the biological markers of this disorder. To confirm the fmdings of this study, data on a prospective follow-up design of neuroleptic-naive patients after neuroleptic treatment will be presented.
249. AUTONOMIC REACTIVITY IN MANIC AND SCHIZOPHRENIC PATIENTS
D.B. Schnur, S. Smith, V. Marte, S. Mukherjee, H.A. Sackiem, A. Bernstein, & A. Smith Mt. Sinai School o f Medicine, N e w York, N Y 10029 We present findings from ongoing work aimed at examining differences in autonomic responsivity between schizophrenic and manic patients presented with attentionally valent stimuli. Neutral and attentionally significant tones were used to determine reactivity of the skin conductance response (SCR) and the fmger pulse amplitude response (FPAR) systems. Thirty-five schizophrenic and 24 manic patients were compared to 29 normals weekly for 4 weeks. In the first and last sessions, subjects were presented with a series of innocuous tones followed by an attentional task requiring a foot pedal response to tones of a given pitch. No stimuli were given during the second and third sessions. For FPAR, the schizophrenic and manic patients had significantly lower response frequencies to the attentional task than the control sample during both testing sessions (Kruskal-Wallis H _> 9.9; p _< 0.007), but patient groups were similar to each other. FPAR frequency to task significant stimuli were highly correlated across sessions (Spearman rho - 0.7; p = 0.0001). There were no between-group differences in SCR frequency to the attentional task or in SCR or FPAR frequency to the neutral tones. Responsivity to task relevant tones was always significantly greater than to neutral tones in both SCR and FPAR (Wilcoxon Z _> 5.2; p = 0.0001). Autonomic reactivity appears reduced in schizophrenic and manic patients when compared to controls, but there do not appear to be differences between patient groups. This relationship is temporally stable but only evident in FPAR when task-relevant tones are being used.
250. EXONIC AND INTRONIC POLYMORPHISMS IN THE DOPAMINE D3 GENE M.A. Crocq I, A. Mayerova 2, F. Duval l, A. Buguet -~, S. Bisser 4, & J.P. Macher I ~Centre Hospitalier, 6 8 2 5 0 R o u f f a c h , France; 2University of Freiburg, 79106 G e r m a n y ; 3CRSSA, 38702 La Tronche, France; 4University of L i m o g e s , France The dopamine D3 receptor is a major target fi)r antipsychotic drugs and forms one subfamily with the D2 and D& A few studies have shown a weak association between schizophrenia and homozygosity at a Bal l polymorphic site in the first exon of the D3 gene; however, this has not been replicated by others, and further studies are necessary. Using PCR we genotyped two di-allelic polymorphisms of the dopamine D3 gene, namely, the known Bal I site in the first exon and a recently localized Msp I site in the fourth intron, in Caucasians from France (n = 101) and Africans from the Republic of Congo (n = 56). At both loci, the predominant allele was different in Caucasians (Bal I allele 1: 0.67; Msp I allele 1: 0.52) and Africans (Bal 1 allele 1: 0.12; Msp I allele 1: 0.24). Within the African group, allelic frequencies did not differ between healthy subjects
BIOL PSYCHIATRY 1995:37:593-683
663
and 25 patients with trypanosomiasis (sleeping sickness). Our results show that Bal I allelic frequencies in the D3 gene display ethnic variations, even though schizophrenia is present in all human cultures. This suggests that, if the Bal I locus is associated with schizophrenia, it might not be causative per se but instead be a marker which is linked to another causative mutation in some populations.
251. INCREASED IL-1 AND IL-3 LR IN SCHIZOPHRENIA P. Sirota 1,3, K. Schild 1,-~, A. Elizur 1,3, M. Djaldetti 2,3, & P. Fishman 2,3 nAbarbanel Mental Health Center, Bat Y a m , Israel; 2Golda Medical Center, Petach T i k v a h , Israel; 3Sackler Faculty o f Medicine, Tel Aviv University, Israel The interleukins play an important role in the development and maintenance of the immune system. Decreased cell-mediated immunity measures were found in schizophrenic patients. The purpose of the present study was to investigate the spontaneous production of interleukin 1 (IL3) and interleukin-3-1ike activity (IL-3-LA) by human mononuelear cells from schizophrenic patients compared to healthy individuals. IL-1 was significantly increased in schizophrenic patients as compared to controls. IL3-LA was slightly elevated in schizophrenic patients as compared to controls. These findings support the hypothesis of an autoimmune dysfunction in some schizophrenic patients.
252. MOTOR PERFORMANCE IN SCHIZOPHRENIA: TREATMENT EFFECTS AND PREDICTIVE VALIDITY J.A. Bates, R.M. Bilder, G. Reiter, A. Koreen, S.H. Geisler, B. Sheitman, M. Chakos, J. Alvir, & J.A. Lieberman Hillside H o s p i t a l - R e s e a r c h , Glen O a k s , N Y 11004 Recent studies have indicated that neuropsychological (NP) measures can be useful predictors of outcome in schizophrenia. Baseline motor performance appears as the most consistent predictive measure across studies; however, most studies so far have examined only baseline performance. The current study focused on motor tasks and their predictive value for determining outcome in schizophrenia. The study examined baseline measures and changes in performance over the first 8 weeks of neuroleptic treatment, to assess the relative contributions to the prediction of outcome. The literature also suggests that neuroleptics may have lateralized effects on motor functioning, and this study provides a unique opportunity to assess this question. The findings corroborate results of other studies in that baseline motor performance predicted outcome (R 2 = 0.21 ). There were significant decrements in motor performance over the first 8 weeks of neuroleptic treatment. There was a trend for treatment-related decrements in motor performance, but these change scores did not add significantly to predictive power based cm pretreatment scores alone. Finally, there were significant lateralized changes in motor performance. Tasks of fine motor coordination (peg placing) showed greater decline in left-sided performance, while simpler tasks of motor speed (finger tapping) showed greater decline in right-sided performance.