- Email: [email protected]
108) POLYMORPHISM AND SCHIZOPHRENIA
Abstracts / Schizophrenia Research 102/1–3, Supplement 2 (2008) 1–279
408 – SEROTONIN TRANSPORTER POLYMORPHISMS AND EARLY RESPONSE TO ANTIPSYCHOTIC TREATMENT IN FIRST-EPISODE OF PSYCHOSIS Javier Vazquez-Bourgon 1 , Maria J Arranz 2 , Ignacio Mata 1 , Jose M Pelayo-Teran 1 , Rocio Perez-Iglesias 1 , Laura Medina-Gonzalez 2 , Eugenio Carrasco-Marin 3 , Jose L Vazquez-Barquero 1 , Benedicto Crespo-Facorro 1 1 University Hospital Marques de Valdecilla. Psychiatry, Santander; 2 Institute of Psychiatry, London; 3 University Hospital Marques de Valdecilla. Immunology, Santander, Spain [email protected] Introduction: There is substantial evidence suggesting that individual variability in antipsychotic treatment response among patients with schizophrenia could be related to genetic variations in neurotransmitter, including serotonin, related genes. Variations in several serotonin transporter (5-HTT) gene polymorphisms have been found to be associated with antipsychotic response among chronic patients with schizophrenia, although their implication in early response among first-episode patients remains unclear. In this study we aimed to address this issue by examining the possible association between variations in three polymorphisms (a VNTR in intron 2, a 44bp insertion/ deletion in the promoter region, and the functional polymorphism rs25531) and early (6 weeks) response to antipsychotic treatment in a sample of 151 patients experiencing their first episode of a non-affective psychosis. No clear association was found between the 5-HTT-VNTR and rs25531 variants and treatment response. However, marginal associations (p<0.05) were observed between 5-HTT-LPR variants and early treatment response among first-episode patients with psychosis, suggesting a minor contribution to antipsychotic drug response of genetic alterations in this gene. References [1] Arranz MJ, Bolonna AA, Munro J, Curtis CJ, Collier DA and Kerwin RW. 2000. The serotonin transporter and Clozapine response. Molecular Psychiatry 5:124-130. [2] Mata I, Arranz MJ, Patiño A, Lai T, Beperet M, Sierrasesumaga L, Clark D, Perez-Nievas F, Richa rds L, Ortuño F, Sham P, Kerwin RW. 2004. Serotonergic polymorphisms and psychotic disorders in populations from North Spain. Am J Med Genet B Neuropsychiatr Genet 126(1):88-94. [3] Tsai SJ, Hong CJ, Yu Y W-T, Lin CH, Songa HL,Lai HC, Yang KH. 2000. Associ ation study of a functional serotonin transporter gene polymorphism with schizophrenia, psychopathology and clozapine response. Schizophrenia Research 44:177-181. [4] Wang L, Yu L, He G, Zhang J, Zhang AP, Du J, Tang RQ, Zhao XZ, Ma J, Xuan JK, Xiao Y, GuN F, Feng GY, Xu MQ, Xing QH, He L. 2007. Response of risperidone treatment may be associated with polymorphisms of HTT gene in Chinese schizophrenia patients. Neuroscience Letters 414:1–4.
409 – ON THE GENETICS OF SCHIZOPHRENIA: USING MATHEMATICAL MODELS TO LEARN FROM EPIDEMIOLOGICAL DATA Carsten Wiuf Bioinformatics Research Center, University of Aarhus, Aarhus C, Denmark [email protected] Introduction: Little is known about the genetics underlying schizophrenia, the number of genes and the interplay between the genes. We aim to get insight into the genetics of schizophrenia by investigating a range of mathematical models and their fit to empirical data. Methods: The models are evaluated by calculating a likelihood-based score of how well they fit observed prevalences from pooled epidemiological studies of families where at least one member suffers from schizophrenia. The models vary with respect to the number of genes, allele frequencies and environmental influence. Results: We show that the data is best explained by models containing
193
few genes in epistasis and that models containing recessive genes generally fit the data better than other models. Another striking feature that transpires from our analysis is that the number of individuals in the general population predisposed to schizophrenia is between 5% and 7% in the best fit model. Conclusions: Compared to a prevalence of 1%, the high frequency of predisposed (5-7%) indicates that the environment has a strong influence on the development of schizophrenia; approximately one in six predisposed develops the disease. Most association studies concentrate on establishing single-gene effects only and do not look for epistatic effects. We have demonstrated that the best fitting models are in fact epistatic models and in consequence it may be difficult to detect susceptibility genes when only looking for single-gene effects.
410 – GENETIC ASSOCIATION BETWEEN THE GAMMA-AMINOBUTYRIC ACID TYPE A RECEPTOR GAMMA2 SUBUNIT GENE AND SCHIZOPHRENIA Clement Zai, Arun Tiwari, Vincenzo De Luca, Greg W.H. Wong, James L. Kennedy Neurogenetics, Centre for Addiciton and Mental Health, Toronto, ON, Canada [email protected] Introduction: Gamma-aminobutyric acid (GABA) is produced in areas of the brain implicated in schizophrenia. The GABAergic system has functional relationships with the glutamatergic and dopaminergic systems. Several genes coding for GABAA subunits, including GABRG2 encoding the γ2 subunit, are clustered at 5q31-q35, a chromosomal region associated with schizophrenia in genome scan studies. Further, GABRG2 interacts directly with the dopamine D5 receptor, making GABRG2 a candidate gene for schizophrenia genetic studies. Methods: We tested five polymorphisms spanning GA BRG2 for association with schizophrenia and also suicidal behaviour. The sample consisted of 109 small nuclear families and 229 schizophrenia cases paired with 229 healthy controls. Results: rs183294 in the 5’ region of GABRG2 was found associated with schizophrenia in both samples with Cover-represented in schizophrenia cases and over-transmitted in schizophrenia families (combined p=3x10-3). Conclusions: Taken together, the results of the present study suggest GABRG2 may be involved in schizophrenia susceptibility, but further studies are required. We are currently genotyping additional polymorphisms spanning GABRG2. We will also be investigating the genetic interaction between GABRG2 and DRD5 in schizophrenia. References [1] Liu, F., Wan, Q., Pristupa, Z.B., Yu, X-M., Wang, Y.T., Niznik, H.B., 2000. Direct protein-protein coupling enables cross-talk between dopamine D5 and g-aminobutyric acid A receptors. Nature. 403 274-280. [2] Sklar, P., Pato, M.T., Kirby, A., Petryshe n, T.L., Medeiros, H., Carvalho, C., Macedo, A., Dourado, A., Coelho, I., Valente, J., Soares, M.J., Ferreira, C.P., Lei, M., Verner, A., Hudson, T.J., Morley, C.P., Kennedy, J.L., Azevedo, M.H., Lander, E., Daly, M.J., Pato, C.N., 2004. Genome-wide scan in Portuguese Island families identifies 5q31-q35 as a susceptibility locus for schizophrenia and psychosis. Mol. Psychiatry. 9 (2) 213-218.
411 – COMT VAL/MET (158/108) POLYMORPHISM AND SCHIZOPHRENIA Ferid Fathalli Research Center Douglas Hospital, Montreal, France [email protected] Introduction: The COMT gene is of particular interest in schizophrenia since corticostriatal dopamine dysregulation is believed to be an important contributor to the pathogenesis of schizophrenia.
194
Abstracts / Schizophrenia Research 102/1–3, Supplement 2 (2008) 1–279
Methods: A case-control study was performed with a sample of 292 schizophrenic patients and 158 control subjects assessed for the COMT Val/Met (158/108) variant. In addition, we carried out a family-based association study with 174 nuclear Caucasian families including 570 persons (133 European ancestry families with 417 individuals and 41 Tunisian –Arab Mediterranean-families including 153 individuals). For the case-control study, we compared allelic and genotype distribution between patients and controls. For the family based study, we used the transmission disequilibrium test (TDT) as implemented in the Fbat program. Results: No differences between patients and control subjects regarding genotype (χ2 = 0.49; df = 2; p=0.78) and allelic frequencies (χ2 = 0.07; df = 1; p = 0.78) were observed. However, in patients with European ancestry, later age at onset (> 25 years) was associated with heterozygosity in males. No difference in genotype and allelic frequencies was found between patients separated according to the quality of the irresponse to conventional neuroleptic. In the family study there was a preferential transmission of the Val allele (high activity) in Tunisian (additive model: Z = 2.2, p = 0.02; dominant model: Z = 3.5, p = 0.0003) but not in European families. Conclus ion: The COMT Val/Met (158/108) polymorphism may play a role in increasing the risk for schizophrenia in some populations. It also could play a role in modulating disease characteristics such as age at onset. Conclusions: Although a positive association between COMT Val/Met polymorphism and the schizophrenia was found in the Tunisian families using a family-based association design, further work is need to validate the role of this polymorphism in this population. The associations between COMT genotypes and age at onset in males may hold some promise since it has been reported by others. Hence, the effect of the COMT Val/met genotype on age at onset of psychotic symptoms in schizophrenia (and possibly other psychotic disorders) merits further investigations.
412 – STUDY OF THE IMPACT OF BIRTH WEIGHT IN ADULT IQ AND NEUROLOGICAL SOFT SIGNS BASED ON HEALTHY TWINS FROM THE BARCELONA UB-TWIN SAMPLE Silvia Alemany 1 , Nadia Vilahur 1 , Mari Aguilera 1 , Ximena Goldberg 1 , Mar Fatjó-Vilas 1 , Araceli Rosa 2 , Lourdes Fañanás 1 1 Universitat de Barcelona, Barcelona, Spain; 2 Universitat Pompeu Fabra, Barcelona, Spain [email protected] Introduction: Prenatal suffering markers such as low birthweight have been related to long-term consequences in both Intelligence Quotient (IQ) and schizophrenia. In the same way, Neurological Soft Signs (NSS) and neurocognitive impairment, seem to appear more frequently in these patients (McGrath and Murray, 2003). The relative importance of the genetic and environmental factors involved in these associations are however, poorly understood. Twin designs allow us to explore that. Methods: NSS (NES; Buchanan and Heinrichs, 1989), estimated IQ (WAIS; Wechsler, 1999) and birthweight were assessed in a preliminary subgroup of 12 MZ (from the Barcelona Twin Sample) and 9 DZ healthy adult twins. Associations between birthweight and i) IQ a nd ii) NSS, were conducted in the whole group using randomly one member of each pair. Additionally, intrapair differences were explored in the DZ and MZ twin groups in order to test whether this association was genetically mediated. Association was performed using correlational analyses. Results: In the whole group, birthweight was associated with IQ (r=0.56, P=0.007) but not with NSS. The importance of environmental and/or genetical factors mediating this association were not detectable in our preliminary analyses in the MZ and in the DZ twin groups. Conclusions: The observed association between birthweight and IQ in our sample is consistent with previous results. Future analysis in a larger sample will allow us to further examine the genetical and environmental contributions to these phenotypes of interest in psychosis.
Acknowledgements: Predoctoral Grant ISCIII (FI07/00272). Supported by EUTwinsS Project (RD-06/0011/0007). References [1] Boomsa, D.I.; van Beijsterveld, C.E.M.; Reitfeld, M. J.H.; Bartels, M.; Van Baal, G.C.M. (2001). Genetics mediate relation of birth weight to childhood IQ. British Medical Journal, 323, 1426-1427. [2] Buchanan, R.W., & Heinrichs, D.W. (1989). The Neurol ogical Evaluation Scale (NES): a structured instrument for the assessment of neurological signs in schizophrenia. Psychiatry Res, 27(3), 335-350. [3] Compton, M.T., Bollini, A.M., McKenzie Mack, L., Kryda, A.D., Rutland, J., Weiss, P.S., Bercu, Z., Ester berg, M.L.,& Walker, E.F. (2007). Neurological soft signs and minor physical anomalies in patients with schizophrenia and related disorders, their first-degree biological relatives, and non-psychiatric controls. Schizophr Res, 94(1-3), 64-73. [4] McGrath, J.J. and Murray, R.M. (2003). Risk factors for schizophrenia: from conception to birth. In S.R. a. W. Hirsch, D. (Ed.), Schizophrenia. Berlin, Germany.: Blackwell Publishing. [5] Newcombe, R., Milne, B.J., Caspi, A., Poulton, R., & Moffitt, T.E. (2007).Bi rthweight predicts IQ: fact or artefact? Twin Res Hum Genet, 10(4), 581-586. [6] Wechsler, D. (1999). Escala de Inteligencia de Wechsler para adultos - III: TEA Ediciones, Madrid.
413 – ASSOCIATION BETWEEN DYSBINDIN (DTNBP1) GENE AND PROACTIVE INTERFERENCE IN VERBAL MEMORY IN SCHIZOPHRENIA AND HEALTHY SUBJECTS M. Alfimova 1 , Mikhail Monakhov 2 , Vera Golimbet 1 , A. Muratova 1 , T. Shemyakina 1 , Svetlana Borozdina 1 , D. Dmitriev 1 , Vadim Karpov 2 1 Mental Health Research Center, Russian Academy of, Moscow; 2 EIMB, Moscow, Russia [email protected] Introduction: Variations in the DTNBP1 gene are thought to be associated with schizophrenia and cognition. Given reports of reductions in DTNBP1 gene expression in the dorsolateral prefrontal cortex and hippocampal formation in schizophrenia, regions crucial for executive functions and memory, relationships between the DTNBP1 gene and these cognitive domains are of particular interest. Methods: The effect SNPs in the DTNBP1 gene (P1763 and P1578) on total number of words recalled, immediate memory and proactive interference, the deleterious effect of previously remembered information on current memory representations, was assessed using MA NCOVA, adjusting for age, in 185 patients with schizophrenia and 229 controls. Results: Mean memory scores differed significantly between patients, relatives, and controls (p <0.001). There was a trend for the association between the P1763 polymorphism and memory performance (p<0.08). The GG homozygotes had inferior scores on all of th e memory measures. After correction for multiple testing the significant result was found only for the proactive interference in the control group (p<0.04). The patients did not differ by genotype on memory performance even after adjusting for symptom scores. Conclusions: Our findings may be cautiously interpreted as suggesting a role of the DTNBP1 gene in the control of the effects of proactive interference mediated by prefrontal cortex. Acknowledgements: This work has been partially supported by RFBR grant 07-04-00140.
408 – SEROTONIN TRANSPORTER POLYMORPHISMS AND EARLY RESPONSE TO ANTIPSYCHOTIC TREATMENT IN FIRST-EPISODE OF PSYCHOSIS Javier Vazquez-Bourgon 1 , Maria J Arranz 2 , Ignacio Mata 1 , Jose M Pelayo-Teran 1 , Rocio Perez-Iglesias 1 , Laura Medina-Gonzalez 2 , Eugenio Carrasco-Marin 3 , Jose L Vazquez-Barquero 1 , Benedicto Crespo-Facorro 1 1 University Hospital Marques de Valdecilla. Psychiatry, Santander; 2 Institute of Psychiatry, London; 3 University Hospital Marques de Valdecilla. Immunology, Santander, Spain [email protected] Introduction: There is substantial evidence suggesting that individual variability in antipsychotic treatment response among patients with schizophrenia could be related to genetic variations in neurotransmitter, including serotonin, related genes. Variations in several serotonin transporter (5-HTT) gene polymorphisms have been found to be associated with antipsychotic response among chronic patients with schizophrenia, although their implication in early response among first-episode patients remains unclear. In this study we aimed to address this issue by examining the possible association between variations in three polymorphisms (a VNTR in intron 2, a 44bp insertion/ deletion in the promoter region, and the functional polymorphism rs25531) and early (6 weeks) response to antipsychotic treatment in a sample of 151 patients experiencing their first episode of a non-affective psychosis. No clear association was found between the 5-HTT-VNTR and rs25531 variants and treatment response. However, marginal associations (p<0.05) were observed between 5-HTT-LPR variants and early treatment response among first-episode patients with psychosis, suggesting a minor contribution to antipsychotic drug response of genetic alterations in this gene. References [1] Arranz MJ, Bolonna AA, Munro J, Curtis CJ, Collier DA and Kerwin RW. 2000. The serotonin transporter and Clozapine response. Molecular Psychiatry 5:124-130. [2] Mata I, Arranz MJ, Patiño A, Lai T, Beperet M, Sierrasesumaga L, Clark D, Perez-Nievas F, Richa rds L, Ortuño F, Sham P, Kerwin RW. 2004. Serotonergic polymorphisms and psychotic disorders in populations from North Spain. Am J Med Genet B Neuropsychiatr Genet 126(1):88-94. [3] Tsai SJ, Hong CJ, Yu Y W-T, Lin CH, Songa HL,Lai HC, Yang KH. 2000. Associ ation study of a functional serotonin transporter gene polymorphism with schizophrenia, psychopathology and clozapine response. Schizophrenia Research 44:177-181. [4] Wang L, Yu L, He G, Zhang J, Zhang AP, Du J, Tang RQ, Zhao XZ, Ma J, Xuan JK, Xiao Y, GuN F, Feng GY, Xu MQ, Xing QH, He L. 2007. Response of risperidone treatment may be associated with polymorphisms of HTT gene in Chinese schizophrenia patients. Neuroscience Letters 414:1–4.
409 – ON THE GENETICS OF SCHIZOPHRENIA: USING MATHEMATICAL MODELS TO LEARN FROM EPIDEMIOLOGICAL DATA Carsten Wiuf Bioinformatics Research Center, University of Aarhus, Aarhus C, Denmark [email protected] Introduction: Little is known about the genetics underlying schizophrenia, the number of genes and the interplay between the genes. We aim to get insight into the genetics of schizophrenia by investigating a range of mathematical models and their fit to empirical data. Methods: The models are evaluated by calculating a likelihood-based score of how well they fit observed prevalences from pooled epidemiological studies of families where at least one member suffers from schizophrenia. The models vary with respect to the number of genes, allele frequencies and environmental influence. Results: We show that the data is best explained by models containing
193
few genes in epistasis and that models containing recessive genes generally fit the data better than other models. Another striking feature that transpires from our analysis is that the number of individuals in the general population predisposed to schizophrenia is between 5% and 7% in the best fit model. Conclusions: Compared to a prevalence of 1%, the high frequency of predisposed (5-7%) indicates that the environment has a strong influence on the development of schizophrenia; approximately one in six predisposed develops the disease. Most association studies concentrate on establishing single-gene effects only and do not look for epistatic effects. We have demonstrated that the best fitting models are in fact epistatic models and in consequence it may be difficult to detect susceptibility genes when only looking for single-gene effects.
410 – GENETIC ASSOCIATION BETWEEN THE GAMMA-AMINOBUTYRIC ACID TYPE A RECEPTOR GAMMA2 SUBUNIT GENE AND SCHIZOPHRENIA Clement Zai, Arun Tiwari, Vincenzo De Luca, Greg W.H. Wong, James L. Kennedy Neurogenetics, Centre for Addiciton and Mental Health, Toronto, ON, Canada [email protected] Introduction: Gamma-aminobutyric acid (GABA) is produced in areas of the brain implicated in schizophrenia. The GABAergic system has functional relationships with the glutamatergic and dopaminergic systems. Several genes coding for GABAA subunits, including GABRG2 encoding the γ2 subunit, are clustered at 5q31-q35, a chromosomal region associated with schizophrenia in genome scan studies. Further, GABRG2 interacts directly with the dopamine D5 receptor, making GABRG2 a candidate gene for schizophrenia genetic studies. Methods: We tested five polymorphisms spanning GA BRG2 for association with schizophrenia and also suicidal behaviour. The sample consisted of 109 small nuclear families and 229 schizophrenia cases paired with 229 healthy controls. Results: rs183294 in the 5’ region of GABRG2 was found associated with schizophrenia in both samples with Cover-represented in schizophrenia cases and over-transmitted in schizophrenia families (combined p=3x10-3). Conclusions: Taken together, the results of the present study suggest GABRG2 may be involved in schizophrenia susceptibility, but further studies are required. We are currently genotyping additional polymorphisms spanning GABRG2. We will also be investigating the genetic interaction between GABRG2 and DRD5 in schizophrenia. References [1] Liu, F., Wan, Q., Pristupa, Z.B., Yu, X-M., Wang, Y.T., Niznik, H.B., 2000. Direct protein-protein coupling enables cross-talk between dopamine D5 and g-aminobutyric acid A receptors. Nature. 403 274-280. [2] Sklar, P., Pato, M.T., Kirby, A., Petryshe n, T.L., Medeiros, H., Carvalho, C., Macedo, A., Dourado, A., Coelho, I., Valente, J., Soares, M.J., Ferreira, C.P., Lei, M., Verner, A., Hudson, T.J., Morley, C.P., Kennedy, J.L., Azevedo, M.H., Lander, E., Daly, M.J., Pato, C.N., 2004. Genome-wide scan in Portuguese Island families identifies 5q31-q35 as a susceptibility locus for schizophrenia and psychosis. Mol. Psychiatry. 9 (2) 213-218.
411 – COMT VAL/MET (158/108) POLYMORPHISM AND SCHIZOPHRENIA Ferid Fathalli Research Center Douglas Hospital, Montreal, France [email protected] Introduction: The COMT gene is of particular interest in schizophrenia since corticostriatal dopamine dysregulation is believed to be an important contributor to the pathogenesis of schizophrenia.
194
Abstracts / Schizophrenia Research 102/1–3, Supplement 2 (2008) 1–279
Methods: A case-control study was performed with a sample of 292 schizophrenic patients and 158 control subjects assessed for the COMT Val/Met (158/108) variant. In addition, we carried out a family-based association study with 174 nuclear Caucasian families including 570 persons (133 European ancestry families with 417 individuals and 41 Tunisian –Arab Mediterranean-families including 153 individuals). For the case-control study, we compared allelic and genotype distribution between patients and controls. For the family based study, we used the transmission disequilibrium test (TDT) as implemented in the Fbat program. Results: No differences between patients and control subjects regarding genotype (χ2 = 0.49; df = 2; p=0.78) and allelic frequencies (χ2 = 0.07; df = 1; p = 0.78) were observed. However, in patients with European ancestry, later age at onset (> 25 years) was associated with heterozygosity in males. No difference in genotype and allelic frequencies was found between patients separated according to the quality of the irresponse to conventional neuroleptic. In the family study there was a preferential transmission of the Val allele (high activity) in Tunisian (additive model: Z = 2.2, p = 0.02; dominant model: Z = 3.5, p = 0.0003) but not in European families. Conclus ion: The COMT Val/Met (158/108) polymorphism may play a role in increasing the risk for schizophrenia in some populations. It also could play a role in modulating disease characteristics such as age at onset. Conclusions: Although a positive association between COMT Val/Met polymorphism and the schizophrenia was found in the Tunisian families using a family-based association design, further work is need to validate the role of this polymorphism in this population. The associations between COMT genotypes and age at onset in males may hold some promise since it has been reported by others. Hence, the effect of the COMT Val/met genotype on age at onset of psychotic symptoms in schizophrenia (and possibly other psychotic disorders) merits further investigations.
412 – STUDY OF THE IMPACT OF BIRTH WEIGHT IN ADULT IQ AND NEUROLOGICAL SOFT SIGNS BASED ON HEALTHY TWINS FROM THE BARCELONA UB-TWIN SAMPLE Silvia Alemany 1 , Nadia Vilahur 1 , Mari Aguilera 1 , Ximena Goldberg 1 , Mar Fatjó-Vilas 1 , Araceli Rosa 2 , Lourdes Fañanás 1 1 Universitat de Barcelona, Barcelona, Spain; 2 Universitat Pompeu Fabra, Barcelona, Spain [email protected] Introduction: Prenatal suffering markers such as low birthweight have been related to long-term consequences in both Intelligence Quotient (IQ) and schizophrenia. In the same way, Neurological Soft Signs (NSS) and neurocognitive impairment, seem to appear more frequently in these patients (McGrath and Murray, 2003). The relative importance of the genetic and environmental factors involved in these associations are however, poorly understood. Twin designs allow us to explore that. Methods: NSS (NES; Buchanan and Heinrichs, 1989), estimated IQ (WAIS; Wechsler, 1999) and birthweight were assessed in a preliminary subgroup of 12 MZ (from the Barcelona Twin Sample) and 9 DZ healthy adult twins. Associations between birthweight and i) IQ a nd ii) NSS, were conducted in the whole group using randomly one member of each pair. Additionally, intrapair differences were explored in the DZ and MZ twin groups in order to test whether this association was genetically mediated. Association was performed using correlational analyses. Results: In the whole group, birthweight was associated with IQ (r=0.56, P=0.007) but not with NSS. The importance of environmental and/or genetical factors mediating this association were not detectable in our preliminary analyses in the MZ and in the DZ twin groups. Conclusions: The observed association between birthweight and IQ in our sample is consistent with previous results. Future analysis in a larger sample will allow us to further examine the genetical and environmental contributions to these phenotypes of interest in psychosis.
Acknowledgements: Predoctoral Grant ISCIII (FI07/00272). Supported by EUTwinsS Project (RD-06/0011/0007). References [1] Boomsa, D.I.; van Beijsterveld, C.E.M.; Reitfeld, M. J.H.; Bartels, M.; Van Baal, G.C.M. (2001). Genetics mediate relation of birth weight to childhood IQ. British Medical Journal, 323, 1426-1427. [2] Buchanan, R.W., & Heinrichs, D.W. (1989). The Neurol ogical Evaluation Scale (NES): a structured instrument for the assessment of neurological signs in schizophrenia. Psychiatry Res, 27(3), 335-350. [3] Compton, M.T., Bollini, A.M., McKenzie Mack, L., Kryda, A.D., Rutland, J., Weiss, P.S., Bercu, Z., Ester berg, M.L.,& Walker, E.F. (2007). Neurological soft signs and minor physical anomalies in patients with schizophrenia and related disorders, their first-degree biological relatives, and non-psychiatric controls. Schizophr Res, 94(1-3), 64-73. [4] McGrath, J.J. and Murray, R.M. (2003). Risk factors for schizophrenia: from conception to birth. In S.R. a. W. Hirsch, D. (Ed.), Schizophrenia. Berlin, Germany.: Blackwell Publishing. [5] Newcombe, R., Milne, B.J., Caspi, A., Poulton, R., & Moffitt, T.E. (2007).Bi rthweight predicts IQ: fact or artefact? Twin Res Hum Genet, 10(4), 581-586. [6] Wechsler, D. (1999). Escala de Inteligencia de Wechsler para adultos - III: TEA Ediciones, Madrid.
413 – ASSOCIATION BETWEEN DYSBINDIN (DTNBP1) GENE AND PROACTIVE INTERFERENCE IN VERBAL MEMORY IN SCHIZOPHRENIA AND HEALTHY SUBJECTS M. Alfimova 1 , Mikhail Monakhov 2 , Vera Golimbet 1 , A. Muratova 1 , T. Shemyakina 1 , Svetlana Borozdina 1 , D. Dmitriev 1 , Vadim Karpov 2 1 Mental Health Research Center, Russian Academy of, Moscow; 2 EIMB, Moscow, Russia [email protected] Introduction: Variations in the DTNBP1 gene are thought to be associated with schizophrenia and cognition. Given reports of reductions in DTNBP1 gene expression in the dorsolateral prefrontal cortex and hippocampal formation in schizophrenia, regions crucial for executive functions and memory, relationships between the DTNBP1 gene and these cognitive domains are of particular interest. Methods: The effect SNPs in the DTNBP1 gene (P1763 and P1578) on total number of words recalled, immediate memory and proactive interference, the deleterious effect of previously remembered information on current memory representations, was assessed using MA NCOVA, adjusting for age, in 185 patients with schizophrenia and 229 controls. Results: Mean memory scores differed significantly between patients, relatives, and controls (p <0.001). There was a trend for the association between the P1763 polymorphism and memory performance (p<0.08). The GG homozygotes had inferior scores on all of th e memory measures. After correction for multiple testing the significant result was found only for the proactive interference in the control group (p<0.04). The patients did not differ by genotype on memory performance even after adjusting for symptom scores. Conclusions: Our findings may be cautiously interpreted as suggesting a role of the DTNBP1 gene in the control of the effects of proactive interference mediated by prefrontal cortex. Acknowledgements: This work has been partially supported by RFBR grant 07-04-00140.