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Molecular-biology of seasonal affective disorder (SAD)
Poster session IT
lOIS
BIOL. PSYClllATRY 1997;42: IS-297S
139-631 Psychiatric morbidity In first-degree relatives of
139-661
A. RuIz, R. Blanco, J. Santander, A. San Martin. Department of Psychiatry BIld Mental Health & Cell. Bioi. and Genetics, School of Medicine, University of Chile, Chile
J.I. Lao, K. Beyer, XA Alvarez, R. Cacabelos. EuroEspes Biomedical Research Center, 15166 Bergondo-La Coruna, Spain
schizophrenic probands
It haS been suggested that genetic factors In schizophrenia have a wide
range of phenotypic expression. The objective of this study was to compare !he risks for psychiatric disorders in first-degree relatives of schizophrenic probands (FDRS) with those of the general population (GP) of Santiago, Chile. Forty-four schizophrenic probands were selected at random, according to the OSM-III-R criteria. All the FORS (247) were interviewed using the CompOSite Intemational Diagnostic Interview and the OSM-III-R check-list. psychiatric morbidity was observed in 56.3% of FORS and In 33.7% d GP, being the difference statistically significant (p < 0.05). Affective d'lSOrders had the highest frequencies, both in FORS and GP (28.3% and 16.29 respectively), the risk was signilicantiy higher in FORS (p < 0.05). Alcoholism and drug abuse disorders had similar risk in FORS (12.9%) and GP (110/0). Morbidity risk (MR) for schizophrenia (3.64%) and Ichizoid-schizotypal personality disorders (2.83%) were significantly higher In FORS than in GP (1.02% and 1.1 % respectively) (p < O.OS), suggesting • biological relationship. The higher MR for affective disorders in FORS must be analysed with caution, considering that some authors postulate that schizophrenia and affective disorders belong to the same continuum.
139-641 An analysis of 0135699 marker alleles for
schizophrenia and schlzoaffective disorders
V.G. Kaleda 1, G.M. Ivanova 2, M.G. Aksenova 2, E.A. Braga 2 , I.V. Ovchinnikov'. ' Mental Health Research Center RAMS, 115522 Moscow. Russia. 2 National Research Center "GNJI Genetika", 113545 Moscow. Russia Similarity and difference of genetic factors underlying main endogenous mental disorders are unknown. Suggestive evidence for linkage between Ichizophrenla and markers on chromosome 13q14.1-q32 were reported (Un et aI.• 1995). PCR-based analysis of the GATG microsatellite marker 0135699 (13q14) for schizophrenic and schizoaffective patients was per• formed to resolve this Issue. Our cohort included OSM-IV schizophrenic (38 persons) and 19 schlzoaffective (persons) patients and 142 healthy controls withoUt psychic pathology. In all groups there was unusual frequency of allele ":r' (216 bp): 0.026, 0.316 and 0.141. Genotype "3"/'3" showed the statisti• cally significant Increase in the group of schizoaffective patients according to xl and g-statistics. The observed frequency of this genotype was 0.158 for lIChlZoaffect/Ve patients, 0.014 for healthy controls and 0.0 for schizophrenic patients. Additional study 01 patients with endogenous psychosis Including bipolar affective disorder will be conducted. Partly supported by Chromo• .erne 13 Group f the Russian Human Genome Project and the Russian Foundation of Basic Research (grant No 95-()4-12170).
139-65] Activation of eRE & SRE In rat brain after electroconvulsive shock
U.G. Kang. S.W. Kim, V.H. Joe, S.H. Jeon " J.B. Park', V.S. Kim. Department of psychiatry, Seoul National University. College of Medicine, Seoul. Korea. 1 Department of Biochemistry. Seoul National University. College of Medicine. Seoul. Korea In order to elucidate the mechanism of Induction of c-fos after electroconvul• live shock (ECS) In rat brain, we have investigated protein binding to CRE and SRE of e-fos S'-flanking sequence after ECS. Methods: Male SoD rats were treated with ECS and hippocampal and cerebellar nuclear extracts were prepared. Mobility shift assay, northern hybridization, immunoblot for ser-133 phosphorylated CREB, kinase assay for SRF fusion protein were performed. Results: e-fos was induced by ECS both in hippocampus and in cere• bellum. Increased protein binding to CRE preceded the induction of e-fos in hippocamPUS but not in cerebellum. CREB phosphorylation was increased only In hippocampus. Increased protein binding to SRE and formation 01 temarY complex (TC) were observed in cerebellum but not in hippocampus. The phoSphorylating activity of nuclear extract to SRF fusion protein was Increased only In the cerebellum. Conclusion: CRE plays major role In hippocampus and SRE plays major role In cerebellum when c-fos Induced after ECS.
Analysis of a polymorphic tetranucleotlde repeat In the TH gene In Spanish psychiatric patients
Results of family, twin and adoption studies carried out by different re• searchers have demonstrated that genetics Is a major etiological factor to be considered In psychiatry. In this regard, several studies have tried to reveal the candidate gene or genes at different points of the genome related to psychiatric disorders. In the case of schizophrenia, mutations In the dopamine transporter gene, or 01-oS dopamine receptor genes have been analysed without successful conclusions. A positive linkage between a polymorphic VNTR region of the human tyrosine hydroxylase (TH) gene and some schizophrenic patients has been recently described. In the present study, we analysed the genotypic frequency of five allelic fragments obtained by polymerase chain reaction (PCR) of the tetranu• cleotide (TCAT) repeat sequence In the first intron of the human TH gene In 4 groups of psychiatric patients [N .. 60, age-range: 42 :I: 12 years (Schizophrenia, N = 20; Anxiety, N .. 20; Depression, N '" 20; Oystimla, N .. 20)), and 1 group of unrelated healthy controls [N .. 64, age-range: 50 :I: 10 years). We conclude that polymorphic VNTR of intron 1 of the TH gene may be linked to a group of schizophrenics in the Spanish population.
139-671
Molecular-biology of seasonal affective disorder (SAD)
E. Lenzinger' , A. Neumeister' , N. Praschak-Rieder', M. Willeit' , T. FOreder 3, K. Fuchs 2, E. Gerhard 2, Th. Stompel, w. Sieghart 2, K. Hornik 3 , S. Kasper', H.N. Aschauer'. ' Department of General Psychiatry. University Hospital for Psychiatry. Austria. 2 Department of Biochemistry, University Hospital for Psychiatry. Austria, 31nstltute for Statistics and Probability Theory. Technical University Vienna, Austria The aim of our study was to Investigate If genotypes of various dppamlne receptor genes, serotonin receptor genes and the serotonin transporter gene are associated with SAD. Furthermore we tested the hypotheses that behavioural effects of short term tryptophan (TRP) depletion can be predicted by the genotypes of the above mentioned receptor genes in SAD patients. Methods: 20 drug free outpatients who fulfilled the criteria for SAD by OSM IV criteria participated In this study. Behavioural effects were measured by HAMO scales beginning 24 hours before and 24 hours after TRP depletion. DNA was extracted from blood samples and PCR were carried out for OR02. OR03, 5HTR2a and HTT. Healthy Controls were matched according to sex and age. Calculations were done by using T-tests. ReSUlts: Preliminary results Indicate the possibility that the SHTR2a receptor gene might be involved In the occurrence of SAD. Allele 1 was found more often In SAD patients than In normal controls (p .. O.OS7). No difference in allelic distribution could be seen for the other markers.
139-681
Genetic polymorphlsms of drug metabolism (Cyp 206) and tardive dyskinesIa In schizophrenia
Shird O. Schindler, Thomas Kapitany, Kurt Meszaros. Elisabeth Lenzlnger, Christian Barnas, Karoline Fuchs, Wemer Sieghart, Harald N. Aschauer, Siegfried Kasper. Department of General Psychiatry. University Hospital, Vienna. Austria Methods: In the present study the occurrence of tardive dyskinesia (TO) in chronic schizophrenic patients was investigated In relation to Cyp 206 alleles. The metabolism 01 Important neuroleptic drugs is influenced by polymorphisms of the Cyp 206 gene which encodes the cytochrome P450 enzyme debrlsoquinelspartein-hydroxylase. Fourty five patients meeting the OSM III-R diagnosis for schizophrenia, chronic course, 29S.xa (a 2 or 4) were recruited. All patients were investigated for showing tardive dyskinesia using the CGI and TORS scale. For genotyping leucocyte DNA of the patients was studied for the occurrence of the most frequent Cyp 206 mutations type A and type B by allele specific PCR-amplification. Results: The Cyp 206 genotype distribution in the patient group did not differ from frequencies In healthy caucasian populations (one patient homozygous type B (2.2%), 14 patients heterozygous type B (31.1%),30 patients homozygous for the normal allele "wild type" (66.7%), no mutation type A). Tardive dyskinesia was found In 23 patients (51.1%). An Influence of the Cyp 206 genotype on the occurrence of TO did only show a trend for significance (p 0.063, mUltiple regression analysis) when a higher
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lOIS
BIOL. PSYClllATRY 1997;42: IS-297S
139-631 Psychiatric morbidity In first-degree relatives of
139-661
A. RuIz, R. Blanco, J. Santander, A. San Martin. Department of Psychiatry BIld Mental Health & Cell. Bioi. and Genetics, School of Medicine, University of Chile, Chile
J.I. Lao, K. Beyer, XA Alvarez, R. Cacabelos. EuroEspes Biomedical Research Center, 15166 Bergondo-La Coruna, Spain
schizophrenic probands
It haS been suggested that genetic factors In schizophrenia have a wide
range of phenotypic expression. The objective of this study was to compare !he risks for psychiatric disorders in first-degree relatives of schizophrenic probands (FDRS) with those of the general population (GP) of Santiago, Chile. Forty-four schizophrenic probands were selected at random, according to the OSM-III-R criteria. All the FORS (247) were interviewed using the CompOSite Intemational Diagnostic Interview and the OSM-III-R check-list. psychiatric morbidity was observed in 56.3% of FORS and In 33.7% d GP, being the difference statistically significant (p < 0.05). Affective d'lSOrders had the highest frequencies, both in FORS and GP (28.3% and 16.29 respectively), the risk was signilicantiy higher in FORS (p < 0.05). Alcoholism and drug abuse disorders had similar risk in FORS (12.9%) and GP (110/0). Morbidity risk (MR) for schizophrenia (3.64%) and Ichizoid-schizotypal personality disorders (2.83%) were significantly higher In FORS than in GP (1.02% and 1.1 % respectively) (p < O.OS), suggesting • biological relationship. The higher MR for affective disorders in FORS must be analysed with caution, considering that some authors postulate that schizophrenia and affective disorders belong to the same continuum.
139-641 An analysis of 0135699 marker alleles for
schizophrenia and schlzoaffective disorders
V.G. Kaleda 1, G.M. Ivanova 2, M.G. Aksenova 2, E.A. Braga 2 , I.V. Ovchinnikov'. ' Mental Health Research Center RAMS, 115522 Moscow. Russia. 2 National Research Center "GNJI Genetika", 113545 Moscow. Russia Similarity and difference of genetic factors underlying main endogenous mental disorders are unknown. Suggestive evidence for linkage between Ichizophrenla and markers on chromosome 13q14.1-q32 were reported (Un et aI.• 1995). PCR-based analysis of the GATG microsatellite marker 0135699 (13q14) for schizophrenic and schizoaffective patients was per• formed to resolve this Issue. Our cohort included OSM-IV schizophrenic (38 persons) and 19 schlzoaffective (persons) patients and 142 healthy controls withoUt psychic pathology. In all groups there was unusual frequency of allele ":r' (216 bp): 0.026, 0.316 and 0.141. Genotype "3"/'3" showed the statisti• cally significant Increase in the group of schizoaffective patients according to xl and g-statistics. The observed frequency of this genotype was 0.158 for lIChlZoaffect/Ve patients, 0.014 for healthy controls and 0.0 for schizophrenic patients. Additional study 01 patients with endogenous psychosis Including bipolar affective disorder will be conducted. Partly supported by Chromo• .erne 13 Group f the Russian Human Genome Project and the Russian Foundation of Basic Research (grant No 95-()4-12170).
139-65] Activation of eRE & SRE In rat brain after electroconvulsive shock
U.G. Kang. S.W. Kim, V.H. Joe, S.H. Jeon " J.B. Park', V.S. Kim. Department of psychiatry, Seoul National University. College of Medicine, Seoul. Korea. 1 Department of Biochemistry. Seoul National University. College of Medicine. Seoul. Korea In order to elucidate the mechanism of Induction of c-fos after electroconvul• live shock (ECS) In rat brain, we have investigated protein binding to CRE and SRE of e-fos S'-flanking sequence after ECS. Methods: Male SoD rats were treated with ECS and hippocampal and cerebellar nuclear extracts were prepared. Mobility shift assay, northern hybridization, immunoblot for ser-133 phosphorylated CREB, kinase assay for SRF fusion protein were performed. Results: e-fos was induced by ECS both in hippocampus and in cere• bellum. Increased protein binding to CRE preceded the induction of e-fos in hippocamPUS but not in cerebellum. CREB phosphorylation was increased only In hippocampus. Increased protein binding to SRE and formation 01 temarY complex (TC) were observed in cerebellum but not in hippocampus. The phoSphorylating activity of nuclear extract to SRF fusion protein was Increased only In the cerebellum. Conclusion: CRE plays major role In hippocampus and SRE plays major role In cerebellum when c-fos Induced after ECS.
Analysis of a polymorphic tetranucleotlde repeat In the TH gene In Spanish psychiatric patients
Results of family, twin and adoption studies carried out by different re• searchers have demonstrated that genetics Is a major etiological factor to be considered In psychiatry. In this regard, several studies have tried to reveal the candidate gene or genes at different points of the genome related to psychiatric disorders. In the case of schizophrenia, mutations In the dopamine transporter gene, or 01-oS dopamine receptor genes have been analysed without successful conclusions. A positive linkage between a polymorphic VNTR region of the human tyrosine hydroxylase (TH) gene and some schizophrenic patients has been recently described. In the present study, we analysed the genotypic frequency of five allelic fragments obtained by polymerase chain reaction (PCR) of the tetranu• cleotide (TCAT) repeat sequence In the first intron of the human TH gene In 4 groups of psychiatric patients [N .. 60, age-range: 42 :I: 12 years (Schizophrenia, N = 20; Anxiety, N .. 20; Depression, N '" 20; Oystimla, N .. 20)), and 1 group of unrelated healthy controls [N .. 64, age-range: 50 :I: 10 years). We conclude that polymorphic VNTR of intron 1 of the TH gene may be linked to a group of schizophrenics in the Spanish population.
139-671
Molecular-biology of seasonal affective disorder (SAD)
E. Lenzinger' , A. Neumeister' , N. Praschak-Rieder', M. Willeit' , T. FOreder 3, K. Fuchs 2, E. Gerhard 2, Th. Stompel, w. Sieghart 2, K. Hornik 3 , S. Kasper', H.N. Aschauer'. ' Department of General Psychiatry. University Hospital for Psychiatry. Austria. 2 Department of Biochemistry, University Hospital for Psychiatry. Austria, 31nstltute for Statistics and Probability Theory. Technical University Vienna, Austria The aim of our study was to Investigate If genotypes of various dppamlne receptor genes, serotonin receptor genes and the serotonin transporter gene are associated with SAD. Furthermore we tested the hypotheses that behavioural effects of short term tryptophan (TRP) depletion can be predicted by the genotypes of the above mentioned receptor genes in SAD patients. Methods: 20 drug free outpatients who fulfilled the criteria for SAD by OSM IV criteria participated In this study. Behavioural effects were measured by HAMO scales beginning 24 hours before and 24 hours after TRP depletion. DNA was extracted from blood samples and PCR were carried out for OR02. OR03, 5HTR2a and HTT. Healthy Controls were matched according to sex and age. Calculations were done by using T-tests. ReSUlts: Preliminary results Indicate the possibility that the SHTR2a receptor gene might be involved In the occurrence of SAD. Allele 1 was found more often In SAD patients than In normal controls (p .. O.OS7). No difference in allelic distribution could be seen for the other markers.
139-681
Genetic polymorphlsms of drug metabolism (Cyp 206) and tardive dyskinesIa In schizophrenia
Shird O. Schindler, Thomas Kapitany, Kurt Meszaros. Elisabeth Lenzlnger, Christian Barnas, Karoline Fuchs, Wemer Sieghart, Harald N. Aschauer, Siegfried Kasper. Department of General Psychiatry. University Hospital, Vienna. Austria Methods: In the present study the occurrence of tardive dyskinesia (TO) in chronic schizophrenic patients was investigated In relation to Cyp 206 alleles. The metabolism 01 Important neuroleptic drugs is influenced by polymorphisms of the Cyp 206 gene which encodes the cytochrome P450 enzyme debrlsoquinelspartein-hydroxylase. Fourty five patients meeting the OSM III-R diagnosis for schizophrenia, chronic course, 29S.xa (a 2 or 4) were recruited. All patients were investigated for showing tardive dyskinesia using the CGI and TORS scale. For genotyping leucocyte DNA of the patients was studied for the occurrence of the most frequent Cyp 206 mutations type A and type B by allele specific PCR-amplification. Results: The Cyp 206 genotype distribution in the patient group did not differ from frequencies In healthy caucasian populations (one patient homozygous type B (2.2%), 14 patients heterozygous type B (31.1%),30 patients homozygous for the normal allele "wild type" (66.7%), no mutation type A). Tardive dyskinesia was found In 23 patients (51.1%). An Influence of the Cyp 206 genotype on the occurrence of TO did only show a trend for significance (p 0.063, mUltiple regression analysis) when a higher
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