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Genetic and non-genetic influence on cognitive functions in schizophrenic twins
X20. Neuropeptides and neuroprotection In conclusion, damage to the brain during early development leads to long-term behavioral changes and to functional activity changes in the brain. The effect of neonatal damage depends on the primary area lesioned since only damage to the amygdala, and not to the ventral hippocampus, affects adult behavior and functional organization of the brain. These data further support this model as a neurodevelopmental model of psychopathological disorders. References
[I] Bachevalier, J. (1994) Medial temporal lobe structures and autism, a review of clinical and experimental findings. Neuropsychologia 32, 627648. [2] Lipska, B.K., Jaskiw, G.E., Weinberger, D.R., 1993, Postpuberal emergence of hyperresponsiveness to stress and to amphetamine after neonatal hippocampal damage, a potential animal model for schizophrenia. Neuropsychopharmacol. 122, 35-43. [3] Weinberger, R.R. (1987) Implications of normal bmin development for the pathogenesis of schizophrenia. Arch. Gen. Psychiatry 44: 660-669. [4] Wolterink G., Daenen, E.W.PM., Dubbeldam, 8, Gerrits, M.A.P.M., Van Rijn, R., Kruse, C.G., Van der Heijden, J., Van Ree, J.M. (2001) Early amygdala damage in the rat as model for neurodevelopmental psychopathological. Eur. Neuropsychopharmacol. 11,5l-59.
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Genetic and non-genetic influence on cognitive functions in schizophrenic twins
M. Weisbrod, C. Kammann, U. Pfbller, S. Schiesser, P. Parzer, M. Spitzer, H. Sauer. University of Heidelberg Department of Psychiatry, Vosse Strasse 4, D-69115 Heidelberg Germany At the advent of the past century Kraepelin described neuropsychological dysfunctions as core symptoms of schizophrenia. Nevertheless, neuropsychological deficits in schizophrenia received not much of scientific interest till the midsixties when Watson et al. (1968) reported that chronic schizophrenic patients show neuropsychological deficits comparable to them found in patients with proved organic brain diseases. Since then it became evident that most of schizophrenic patients suffer from at least moderate neuropsychological dysfunctions. These findings attracted even more attention when it was shown that neuropsychological status is an important predictor for long term outcome in schizophrenia. Although deficits were reported for nearly all neuropsychological domains, most consistent were the findings for attention, memory and executive functions. In contrast to Kraepelin dementia precox concept neuropsychological deficits do not deteriorate consistently. They are present before the onset of pathognomonic schizophrenic symptoms and persist during remission. Therefore, neuropsychological deficits may represent trait markers which may reflect vulnerability. Since neuropsychological deficits were also found in non-schizophrenic relatives of schizophrenic patients and in patients suffering from schizophrenia spectrum disorders, they may represent phenotypic markers of genes which are associated with schizophrenia. Nevertheless, neuropsychological deficits are also modulated by the state. Studies on monozygotic twins discordant for schizophrenia found more pronounced deficits in the schizophrenic compared to the non-schizophrenic twin. Therefore, both environmental factors and state seem to modulate neuropsychological deficits in schizophrenia. The aim of this study was to disentangle environmental and genetic influences on neuropsychological deficits which are typically found in schizophrenic patients. Therefore, mono- (mz) and dizygotic (dz) twin pairs with at least one twin suffering from
s153
schizophrenia spectrum disorder (indexpairs) were compared to healthy control twins in respect to attention, memory functions, face comparison and executive control functions. Since dz and mz twin pairs have different and defined genetic overlap the examination of dz as well as mz pairs allows to estimate the differential impact of genetic and environmental factors on the observed neuropsychological deficits. The final study group consisted of 28 index and 21 control pairs. Index pairs consisted of 20 discordant pairs (11 mz and 9 dz) and 8 concordant pairs (6 mz and 2 dz). Diagnoses were established by the Schedules for Clinical Assessment in Neuropsychiatry (SCAN; World Health Organisation 1992) based on an extensive interview. Twins were regarded as discordant if the index twin was diagnosed with schizophrenia (F20 according to ICD lo), schizoaffective disorder (F25 according to ICD 10) or schizotypal personality disorder (F21 according to ICD 10) and the co-twin revealed either no psychiatric diagnosis (n = 15) or a non-F2 diagnosis (3 x F32, 1 x F31, 1 x F40). Twins were regarded as concordant if both twins were diagnosed with schizophrenia spectrum disorder. The 21 control pairs consisted of 19 mz and 2 dz pairs and were matched to the index pairs in respect to sex, age, and verbal intelligence. Neither index nor control pairs suffered from organic brain diseases. Informed consent was obtained and the study design was approved by the local ethic committee. Neuropsychological functions were assessed with the Continuous Performing Test (CPT: attention), spatial delayed response test (SDRT: working memory), subtests of the Syndrom-Kurztest (SKT: semantic memory), Tower-of-TorontoTest (ToTT: procedural memory), Heidelberg Face Recognition Test (face recognition) and the Wisconsin Card Sorting Test (WCST: problem solving). Data were analyzed using multiple regression and logistic regression models. The obtained results suggest that SDRT and SKT provide viable vulnerability markers whereas ToTT, WCST, and CPT have a certain potential to serve as vulnerability markers. The results on semantic memory testing yields a pattern compatible with a genetic trait. In contrast the tindings on SDRT suggests the influence of environmental factors. Moreover, dizygotic and monozygotic index pairs differed in respect to the pattern of neuropsychological deficits. Similarly concordant and discordant pairs showed different patterns. Therefore, schizophrenic subgroups with different genetic load may exhibit distinct patterns of neuropsychological deficits.
S.20. Neuropeptides and neuroprotection [s.20.011Development
of neuropeptide systems: Lessons from the hypothalamoneurohypophysial system
J.P.H. Burbach. Department of Pharmacology, Rudolf Magnus Institute for Neunxciences, Universi@ Medical Center Utrecht, Utrecht, The Netherlands Neuropeptides are signaling molecules that mediate regulated communication between neurons. In this way they can transmit primary neuronal activity, for instance in pain sensation, but more often they modulate ongoing communication in subtle ways. This allows neuropeptides to fine tune neuronal activity, thereby influencing set-points in complex physiological processes. Thus, the biological significance of neuropeptides is rather in adaptive and plastic modulation of brain functions than in primary
[I] Bachevalier, J. (1994) Medial temporal lobe structures and autism, a review of clinical and experimental findings. Neuropsychologia 32, 627648. [2] Lipska, B.K., Jaskiw, G.E., Weinberger, D.R., 1993, Postpuberal emergence of hyperresponsiveness to stress and to amphetamine after neonatal hippocampal damage, a potential animal model for schizophrenia. Neuropsychopharmacol. 122, 35-43. [3] Weinberger, R.R. (1987) Implications of normal bmin development for the pathogenesis of schizophrenia. Arch. Gen. Psychiatry 44: 660-669. [4] Wolterink G., Daenen, E.W.PM., Dubbeldam, 8, Gerrits, M.A.P.M., Van Rijn, R., Kruse, C.G., Van der Heijden, J., Van Ree, J.M. (2001) Early amygdala damage in the rat as model for neurodevelopmental psychopathological. Eur. Neuropsychopharmacol. 11,5l-59.
-1
Genetic and non-genetic influence on cognitive functions in schizophrenic twins
M. Weisbrod, C. Kammann, U. Pfbller, S. Schiesser, P. Parzer, M. Spitzer, H. Sauer. University of Heidelberg Department of Psychiatry, Vosse Strasse 4, D-69115 Heidelberg Germany At the advent of the past century Kraepelin described neuropsychological dysfunctions as core symptoms of schizophrenia. Nevertheless, neuropsychological deficits in schizophrenia received not much of scientific interest till the midsixties when Watson et al. (1968) reported that chronic schizophrenic patients show neuropsychological deficits comparable to them found in patients with proved organic brain diseases. Since then it became evident that most of schizophrenic patients suffer from at least moderate neuropsychological dysfunctions. These findings attracted even more attention when it was shown that neuropsychological status is an important predictor for long term outcome in schizophrenia. Although deficits were reported for nearly all neuropsychological domains, most consistent were the findings for attention, memory and executive functions. In contrast to Kraepelin dementia precox concept neuropsychological deficits do not deteriorate consistently. They are present before the onset of pathognomonic schizophrenic symptoms and persist during remission. Therefore, neuropsychological deficits may represent trait markers which may reflect vulnerability. Since neuropsychological deficits were also found in non-schizophrenic relatives of schizophrenic patients and in patients suffering from schizophrenia spectrum disorders, they may represent phenotypic markers of genes which are associated with schizophrenia. Nevertheless, neuropsychological deficits are also modulated by the state. Studies on monozygotic twins discordant for schizophrenia found more pronounced deficits in the schizophrenic compared to the non-schizophrenic twin. Therefore, both environmental factors and state seem to modulate neuropsychological deficits in schizophrenia. The aim of this study was to disentangle environmental and genetic influences on neuropsychological deficits which are typically found in schizophrenic patients. Therefore, mono- (mz) and dizygotic (dz) twin pairs with at least one twin suffering from
s153
schizophrenia spectrum disorder (indexpairs) were compared to healthy control twins in respect to attention, memory functions, face comparison and executive control functions. Since dz and mz twin pairs have different and defined genetic overlap the examination of dz as well as mz pairs allows to estimate the differential impact of genetic and environmental factors on the observed neuropsychological deficits. The final study group consisted of 28 index and 21 control pairs. Index pairs consisted of 20 discordant pairs (11 mz and 9 dz) and 8 concordant pairs (6 mz and 2 dz). Diagnoses were established by the Schedules for Clinical Assessment in Neuropsychiatry (SCAN; World Health Organisation 1992) based on an extensive interview. Twins were regarded as discordant if the index twin was diagnosed with schizophrenia (F20 according to ICD lo), schizoaffective disorder (F25 according to ICD 10) or schizotypal personality disorder (F21 according to ICD 10) and the co-twin revealed either no psychiatric diagnosis (n = 15) or a non-F2 diagnosis (3 x F32, 1 x F31, 1 x F40). Twins were regarded as concordant if both twins were diagnosed with schizophrenia spectrum disorder. The 21 control pairs consisted of 19 mz and 2 dz pairs and were matched to the index pairs in respect to sex, age, and verbal intelligence. Neither index nor control pairs suffered from organic brain diseases. Informed consent was obtained and the study design was approved by the local ethic committee. Neuropsychological functions were assessed with the Continuous Performing Test (CPT: attention), spatial delayed response test (SDRT: working memory), subtests of the Syndrom-Kurztest (SKT: semantic memory), Tower-of-TorontoTest (ToTT: procedural memory), Heidelberg Face Recognition Test (face recognition) and the Wisconsin Card Sorting Test (WCST: problem solving). Data were analyzed using multiple regression and logistic regression models. The obtained results suggest that SDRT and SKT provide viable vulnerability markers whereas ToTT, WCST, and CPT have a certain potential to serve as vulnerability markers. The results on semantic memory testing yields a pattern compatible with a genetic trait. In contrast the tindings on SDRT suggests the influence of environmental factors. Moreover, dizygotic and monozygotic index pairs differed in respect to the pattern of neuropsychological deficits. Similarly concordant and discordant pairs showed different patterns. Therefore, schizophrenic subgroups with different genetic load may exhibit distinct patterns of neuropsychological deficits.
S.20. Neuropeptides and neuroprotection [s.20.011Development
of neuropeptide systems: Lessons from the hypothalamoneurohypophysial system
J.P.H. Burbach. Department of Pharmacology, Rudolf Magnus Institute for Neunxciences, Universi@ Medical Center Utrecht, Utrecht, The Netherlands Neuropeptides are signaling molecules that mediate regulated communication between neurons. In this way they can transmit primary neuronal activity, for instance in pain sensation, but more often they modulate ongoing communication in subtle ways. This allows neuropeptides to fine tune neuronal activity, thereby influencing set-points in complex physiological processes. Thus, the biological significance of neuropeptides is rather in adaptive and plastic modulation of brain functions than in primary