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P.1.a.013 Association study of single nucleotide polymorphisms on catechol-O-methyltransferase gene in Korean patients with schizophrenia
S234
P.1.a Basic neuroscience – Genetics and genomics
P.1.a.012 Lack of association between dopamine D3 receptor Ser9Gly polymorphism and schizophrenia in Han Chinese H.S.Y. Huang1 ° , C.H.A. Chang1 , L.W.W. Lin1 , S.M.J. Shy1 , H.C.C. Huang1 , L.R.B. Lu2 . 1 National Defense Medical Center Tri-Service General Hospital, Psychiatry, Taipei, Taiwan; 2 College of Medicine National Chen Kung University, Psychiatry, Tainan, Taiwan Objectives: The dopamine D3 receptor (DRD3) is considered as potentially relevant to the pathogenesis of schizophrenia because of its localization to the limbic system of the brain and because of its possible mediating effect on the therapeutic action of antipsychotic drugs. The Ser9Gly polymorphism in dopamine D3 receptor gene was also considered an important factor in the pathogenesis of schizophrenia. Allele and genotype frequencies of this polymorphism were studied in different ethnic groups of schizophrenic patients. However, the results have been inconclusive. The aim of this study is to investigate whether the DRD3 Ser9Gly polymorphism is associated with an increased genetic risk for schizophrenia. We also characterize the influence of DRD3 on symptom severity in acutely ill schizophrenia patients. Methods: We recruited 256 schizophrenic patients and 285 normal controls matched for gender, age and ethnicity. Pretreatment psychotic symptoms were evaluated with the PANSS in 128 acutely exacerbated schizophrenic inpatients. Genotyping of Ser9Gly polymorphism was performed with a PCR-RFLP method and reconfirmed by a direct sequencing technique. HardyWeinberg equilibrium was assessed for each group, and the frequencies of genotype and allele were also compared in patients versus controls using Pearson x2 analyses. Results: The distribution for the genotype of the DRD3 Ser9Gly polymorphism for both groups was described by the Hardy–Weinberg equilibrium (P > 0.1). The frequencies of genotype and allele in the DRD3 Ser9Gly polymorphism were not significantly different between patients and healthy controls. In addition, comparisons of the clinical subgroups of schizophrenic patients and normal controls according to the genotype distributions and allele frequencies of the DRD3 Ser9Gly polymorphism showed no significant difference. Using multiple logistic regression analyses, we confirmed that the there was still no association between either schizophrenia or its clinical subgroups and the DRD3 Ser9Gly polymorphism after correction for age and gender (Table 3). In the 128 acutely exacerbated schizophrenic inpatients, the mean (±standard deviation) PANSS global, positive, negative and general symptoms scores were 95.0 (±11.8), 21.8 (±3.5), 21.0 (±4.2), and 52.3 (±7.4), respectively. There were no significant differences in age, gender, age of onset, duration of illness, or PANSS items scores among the three Ser9Gly genotype groups. Conclusions: Although the DRD3 Ser9Gly polymorphism has been postulated as an important factor in schizophrenia, there is no consistent evidence that this polymorphism increased the risk of schizophrenia. The results presented here suggest that the DRD3 Ser9Gly polymorphism does not play a major role in increasing susceptibility to schizophrenia and its clinical subgroups among Han Chinese. Still, there is a possibility that the DRD3 Ser9Gly variant may reflect genetic variation of severity of positive symptoms in acutely exacerbated schizophrenia. Further studies investigating the effect of the DRD3 Ser9Gly polymorphism in relation to longer time course of schizophrenia, including treatment response to antipsychotics, are warranted.
References [1] Jonsson EG, Flyckt L, Burgert E, Crocq MA, Forslund K, MattilaEvenden M, Rylander G, Asberg M, Nimgaonkar VL, Edman G, Bjerkenstedt L, Wiesel FA, Sedvall GC, 2003, Dopamine D3 receptor gene Ser9Gly variant and schizophrenia: association study and metaanalysis. Psychiatr Genet 13, 1−12. [2] Segman R, Neeman T, Heresco-Levy U, Finkel B, Karagichev L, Schlafman M, Dorevitch A, Yakir A, Lerner A, Shelevoy A, Lerer B, 1999, Genotypic association between the dopamine D3 receptor and tardive dyskinesia in chronic schizophrenia. Mol Psychiatry 4, 247– 253. [3] Talkowski ME, Mansour H, Chowdari KV, Wood J, Butler A, Varma PG, Prasad S, Semwal P, Bhatia T, Deshpande S, Devlin B, Thelma BK, Nimgaonkar VL, 2006, Novel, replicated associations between dopamine D3 receptor gene polymorphisms and schizophrenia in two independent samples. Biol Psychiatry 60, 570–577
P.1.a.013 Association study of single nucleotide polymorphisms on catechol-Omethyltransferase gene in Korean patients with schizophrenia K. Chulkwon ° , J.W. Kim, D.K. Lee. Dong-A University Hospital, psychiatry, Busan, South-Korea Objective: The purpose of this research is twofold. One is the association study to find out a genetic association between COMT gene and Korean schizophrenics. Catechol-O-methyltransferase (COMT) is the enzyme that plays an important role in metabolizing catecholamines including dopamine, and COMT gene has been investigated as a candidate gene for schizophrenia. Recently, a lot of association between several single nucleotide polymorphism (SNP)s on COMT gene and schizophrenia have been suggested. The other is to investigated MTHFR C677T, A1298C polymorphism whether this enzyme is related with etiology of schizophrenia. The mechanism of schizophrenia is not revealed clearly, but some studies have provided the hypothesis that MTHFR may play a role on the basis of homeostasis of CNS or it’s components. Methods: we selected four SNPs through even spacing and minor allele frequency from 90 normal controls after abstracting DNAs from 366 patients diagnosed as schizophrenia and 359 normal controls matched with age and gender. Subjects included in this study were chronic schizophrenic patients discharged from closed ward who met DSM-IV criteria for schizophrenia. Patients were excluded from this study if they were beyond the age range of 15 to 45 years, presented evidence of organic brain syndrome, had a mental retardation, had a recent history of alcohol or substance abuse, and had serious concurrent medical illness. Genetic analysis was done by using SNP stream 25K system. Allele frequencies, genotype frequencies and haplotype frequencies were compared between two groups. Moreover, subgroups were built on the basis of onset age, and allele frequencies and genotype frequencies were compared among subgroups individually. Results: In rs2020917 of female patients among four SNPs which were found, significant difference (P = 0.0224) of genotype frequencies was noted, but that of haplotype frequencies in four SNPs was not noted between patients and controls. Significant difference of allele frequencies for rs1544325 according to onset age was noted, and significant difference of allele and genotype frequencies for rs 1544325 according to onset age in female patients were also noted. In genotype difference in dominant model of rs2020917, rs1544325, rs4680, rs165599, there was no significant odds ratio between schizophrenics and normal controls. In genotype difference in recessive model of rs2020917, rs1544325,
P.1.a Basic neuroscience – Genetics and genomics rs4680, rs165599, there was no significant odds ratio between schizophrenics and normal controls. There was no significant differences between schizophrenics and normal controls in the frequency of allele for the four SNPs of the COMT gene, the frequency of genotype for the four SNPs of the COMT gene and the frequency of haplotype. Gene variation of MTHFR C677T, A1298C was analysised, but we can not find any significant differences of gene-distribution, alleles distribution, genotype and haplotype. And we also cannot find the significant differences between their alleles and onset-age in MTHFR C677T, A1298C. Conclusion: Genetic association between four SNPs on COMT gene and Korean schizophrenics was generally not to be found in this study but our finding is suggestive of genetic components for gender-specificity and onset age in Korean schizophrenics. We suggest that MTHFR C677T, MTHFR A1298C genotypes are not related to the risk factors for schizophrenia References [1] Daniels NM, Williams J, Jones LA, Cardno AG, Murhy KC, Spurlock G, Riley B, Scambler P, Asherson P, McGuffin P, Owen MJ, 1996, NO evidence for allelic association between schizophrenia and a polymorphism determining high or low catechol-O-methyltransferase activity. Am J Psychiatry 153, 268–270. [2] Karayiorgou M, Gogos JA, Galke BL, Wolyniec PS, Nestadt G, Antonarakis SE, Kazazian HH, Housman DE, Pulver AE, 1998, Identification of sequence variants and analysis of the role of the catechol-Omethyltransferase gene in schizophrenia susceptibility. Biol Psychiatry 43, 425–431. [3] Strous RD, Bark N, Woerner M, Lachman HM, 1997 Lack of association of a functional catechol-O-methyltransferase gene polymorphism in schizophrenia. Biol Psychiatry 41, 493–495.
P.1.a.014 No association of CCK promoter gene −36C>T polymorphism and panic disorder in the Korean population
S235
attack scores during the previous one month, as well as scores for anticipatory anxiety, panic distress, and agoraphobic distress, as determined by a visual analogue scale (VAS). And all the subjects were recommended to complete the measures such as STAI-S, STAI-T, BDI, SCL-90-R, ASI-R, CGI-S, PDSS, and (HAMD). Responder analyses were conducted on the basis of changes in CGI-I scores after 10 weeks of treatment. Results: The distribution of genotype is within the range of Hardy-Weinberg equilibrium in both panic group and control. Genotype and allele distribution of CCK promoter −36C>T polymorphism patients with panic disorder was not significantly different from those of the controls. In addition, after excluding panic disorder patients with major depressive disorder, we did not find out the association of CCK −36C>T with the panic disorder without comorbidities. In analysis for determine the difference of 10 week-pharmacotherapeutic response according to genotype, CGI-I scores did not significantly differ among the genotypes of CCK promoter −36C>T polymorphism. When we subdivided the patients into responders (CGI-I: 1−2) and non-responders (CGI-I: 3−7), we found no differences between the groups with regard to genotypic and allelic frequencies. Conclusion: This study suggested that the CCK promoter −36C>T polymorphism may have not a potential role for susceptibility to panic disorder in the Korean population. And the response to 10 week-pharmacotherapy is not different according to the genotype of CCK promoter −36C>T polymorphism. Thus calls for consecutive studies in order to pile up the data with larger different ethnic background. References [1] Wang Z, Valdes J, Noyes R, Zoega T, Crowe RR, 1998, Possible association of a cholecystokinin promoter polymorphism (CCK-36CT) with panic disorder. Am J Med Genet (Neuropshchiatr Genet) 81, 228– 234. [2] Kennedy JL, Bradwejn J, Koszychi D, King N, Crowe R, Vincent J, et al, 1999, Investigation of cholecystokinin system genes in panic disorder. Mol Psychiatry 4, 284–285.
W. Kim ° , J.M. Woo. Seoul Paik Hospital, Department of Psychiatry, Seoul, South-Korea Objective: Panic disorder is a common anxiety disorder with a lifetime prevalence of 1−3%, and characterized as many somatic symptoms combined with severe anxiety, including fears of going crazy or dying. There were researches about the biological basis of panic disorder, which suggested some physiological factors are closely related with panic attack or susceptibility of anxiety. Lactate infusion, m-chlorophenylpiperazine infusion, tryptophan depletion and cholecystokinin infusion is known to induce anxiety. Among these, cholecyctokinin (CCK), peptide located mainly in brain and digestive system, is reported to have interactions with dopamine and related with various physiologic properties such as anxiety, appetite, respiration, sleep. Some genetic polymorphisms of these anxiety-related physiologic agents have been reported to related with panic disorder. Recently, possible association of CCK promoter gene −36C>T was reported in Caucasian. Therefore, we aimed to test the possible association between cholecystokinin(CCK) promoter gene −36C>T polymorphism and panic disorder in Korean population. Methods: 267 patients with panic disorder and 82 healthy controls participated in this study. Genotyping was performed by polymerase chain reaction-based method. Chip-based MALDITOF (matrix assisted laser desorption ionization time of flight) mass spectrometry platform was applied in analysis. The severity of the patients’ panic disorders was assessed according to panic
P.1.a.015 Neuregulin-1 risk haplotype and eye movements in schizophrenia M. Haraldsson1 ° , U. Ettinger2 , B.B. Magnusdottir1 , T. Sigmundsson1 , E. Sigurdsson1 , H. Petursson1 . 1 LandspitaliUniversity Hospital, Psychiatry, Reykjavik, Iceland; 2 Institute of Psychiatry, Center for Neuroimaging Sciences, London, United Kingdom Aim: To investigate effects of the Neuregulin-1 (NRG-1) “atrisk” haplotype on antisaccade (AS) and smooth pursuit (SP) eye movements in schizophrenia patients and healthy controls. Background: Recent studies provide evidence for an association between variations in the NRG-1 gene and schizophrenia (Stefansson et al. 2002). NRG-1 has multiple roles in the central nervous system including neuronal migration, synapse formation and expression of the NMDA glutamate receptor. The phenotypic heterogeneity of schizophrenia complicates studies of how NRG-1 and other potential risk genotypes affect the disease phenotype. This problem may be circumvented by studying endophenotypes. Endophenotypes are biological or behavioural features which may be more closely related to underlying disease genes than the complex clinical phenotype (Braff et al. 2007). Deficits in AS and SP eye movements are promising endophenotypes in genetic studies
P.1.a Basic neuroscience – Genetics and genomics
P.1.a.012 Lack of association between dopamine D3 receptor Ser9Gly polymorphism and schizophrenia in Han Chinese H.S.Y. Huang1 ° , C.H.A. Chang1 , L.W.W. Lin1 , S.M.J. Shy1 , H.C.C. Huang1 , L.R.B. Lu2 . 1 National Defense Medical Center Tri-Service General Hospital, Psychiatry, Taipei, Taiwan; 2 College of Medicine National Chen Kung University, Psychiatry, Tainan, Taiwan Objectives: The dopamine D3 receptor (DRD3) is considered as potentially relevant to the pathogenesis of schizophrenia because of its localization to the limbic system of the brain and because of its possible mediating effect on the therapeutic action of antipsychotic drugs. The Ser9Gly polymorphism in dopamine D3 receptor gene was also considered an important factor in the pathogenesis of schizophrenia. Allele and genotype frequencies of this polymorphism were studied in different ethnic groups of schizophrenic patients. However, the results have been inconclusive. The aim of this study is to investigate whether the DRD3 Ser9Gly polymorphism is associated with an increased genetic risk for schizophrenia. We also characterize the influence of DRD3 on symptom severity in acutely ill schizophrenia patients. Methods: We recruited 256 schizophrenic patients and 285 normal controls matched for gender, age and ethnicity. Pretreatment psychotic symptoms were evaluated with the PANSS in 128 acutely exacerbated schizophrenic inpatients. Genotyping of Ser9Gly polymorphism was performed with a PCR-RFLP method and reconfirmed by a direct sequencing technique. HardyWeinberg equilibrium was assessed for each group, and the frequencies of genotype and allele were also compared in patients versus controls using Pearson x2 analyses. Results: The distribution for the genotype of the DRD3 Ser9Gly polymorphism for both groups was described by the Hardy–Weinberg equilibrium (P > 0.1). The frequencies of genotype and allele in the DRD3 Ser9Gly polymorphism were not significantly different between patients and healthy controls. In addition, comparisons of the clinical subgroups of schizophrenic patients and normal controls according to the genotype distributions and allele frequencies of the DRD3 Ser9Gly polymorphism showed no significant difference. Using multiple logistic regression analyses, we confirmed that the there was still no association between either schizophrenia or its clinical subgroups and the DRD3 Ser9Gly polymorphism after correction for age and gender (Table 3). In the 128 acutely exacerbated schizophrenic inpatients, the mean (±standard deviation) PANSS global, positive, negative and general symptoms scores were 95.0 (±11.8), 21.8 (±3.5), 21.0 (±4.2), and 52.3 (±7.4), respectively. There were no significant differences in age, gender, age of onset, duration of illness, or PANSS items scores among the three Ser9Gly genotype groups. Conclusions: Although the DRD3 Ser9Gly polymorphism has been postulated as an important factor in schizophrenia, there is no consistent evidence that this polymorphism increased the risk of schizophrenia. The results presented here suggest that the DRD3 Ser9Gly polymorphism does not play a major role in increasing susceptibility to schizophrenia and its clinical subgroups among Han Chinese. Still, there is a possibility that the DRD3 Ser9Gly variant may reflect genetic variation of severity of positive symptoms in acutely exacerbated schizophrenia. Further studies investigating the effect of the DRD3 Ser9Gly polymorphism in relation to longer time course of schizophrenia, including treatment response to antipsychotics, are warranted.
References [1] Jonsson EG, Flyckt L, Burgert E, Crocq MA, Forslund K, MattilaEvenden M, Rylander G, Asberg M, Nimgaonkar VL, Edman G, Bjerkenstedt L, Wiesel FA, Sedvall GC, 2003, Dopamine D3 receptor gene Ser9Gly variant and schizophrenia: association study and metaanalysis. Psychiatr Genet 13, 1−12. [2] Segman R, Neeman T, Heresco-Levy U, Finkel B, Karagichev L, Schlafman M, Dorevitch A, Yakir A, Lerner A, Shelevoy A, Lerer B, 1999, Genotypic association between the dopamine D3 receptor and tardive dyskinesia in chronic schizophrenia. Mol Psychiatry 4, 247– 253. [3] Talkowski ME, Mansour H, Chowdari KV, Wood J, Butler A, Varma PG, Prasad S, Semwal P, Bhatia T, Deshpande S, Devlin B, Thelma BK, Nimgaonkar VL, 2006, Novel, replicated associations between dopamine D3 receptor gene polymorphisms and schizophrenia in two independent samples. Biol Psychiatry 60, 570–577
P.1.a.013 Association study of single nucleotide polymorphisms on catechol-Omethyltransferase gene in Korean patients with schizophrenia K. Chulkwon ° , J.W. Kim, D.K. Lee. Dong-A University Hospital, psychiatry, Busan, South-Korea Objective: The purpose of this research is twofold. One is the association study to find out a genetic association between COMT gene and Korean schizophrenics. Catechol-O-methyltransferase (COMT) is the enzyme that plays an important role in metabolizing catecholamines including dopamine, and COMT gene has been investigated as a candidate gene for schizophrenia. Recently, a lot of association between several single nucleotide polymorphism (SNP)s on COMT gene and schizophrenia have been suggested. The other is to investigated MTHFR C677T, A1298C polymorphism whether this enzyme is related with etiology of schizophrenia. The mechanism of schizophrenia is not revealed clearly, but some studies have provided the hypothesis that MTHFR may play a role on the basis of homeostasis of CNS or it’s components. Methods: we selected four SNPs through even spacing and minor allele frequency from 90 normal controls after abstracting DNAs from 366 patients diagnosed as schizophrenia and 359 normal controls matched with age and gender. Subjects included in this study were chronic schizophrenic patients discharged from closed ward who met DSM-IV criteria for schizophrenia. Patients were excluded from this study if they were beyond the age range of 15 to 45 years, presented evidence of organic brain syndrome, had a mental retardation, had a recent history of alcohol or substance abuse, and had serious concurrent medical illness. Genetic analysis was done by using SNP stream 25K system. Allele frequencies, genotype frequencies and haplotype frequencies were compared between two groups. Moreover, subgroups were built on the basis of onset age, and allele frequencies and genotype frequencies were compared among subgroups individually. Results: In rs2020917 of female patients among four SNPs which were found, significant difference (P = 0.0224) of genotype frequencies was noted, but that of haplotype frequencies in four SNPs was not noted between patients and controls. Significant difference of allele frequencies for rs1544325 according to onset age was noted, and significant difference of allele and genotype frequencies for rs 1544325 according to onset age in female patients were also noted. In genotype difference in dominant model of rs2020917, rs1544325, rs4680, rs165599, there was no significant odds ratio between schizophrenics and normal controls. In genotype difference in recessive model of rs2020917, rs1544325,
P.1.a Basic neuroscience – Genetics and genomics rs4680, rs165599, there was no significant odds ratio between schizophrenics and normal controls. There was no significant differences between schizophrenics and normal controls in the frequency of allele for the four SNPs of the COMT gene, the frequency of genotype for the four SNPs of the COMT gene and the frequency of haplotype. Gene variation of MTHFR C677T, A1298C was analysised, but we can not find any significant differences of gene-distribution, alleles distribution, genotype and haplotype. And we also cannot find the significant differences between their alleles and onset-age in MTHFR C677T, A1298C. Conclusion: Genetic association between four SNPs on COMT gene and Korean schizophrenics was generally not to be found in this study but our finding is suggestive of genetic components for gender-specificity and onset age in Korean schizophrenics. We suggest that MTHFR C677T, MTHFR A1298C genotypes are not related to the risk factors for schizophrenia References [1] Daniels NM, Williams J, Jones LA, Cardno AG, Murhy KC, Spurlock G, Riley B, Scambler P, Asherson P, McGuffin P, Owen MJ, 1996, NO evidence for allelic association between schizophrenia and a polymorphism determining high or low catechol-O-methyltransferase activity. Am J Psychiatry 153, 268–270. [2] Karayiorgou M, Gogos JA, Galke BL, Wolyniec PS, Nestadt G, Antonarakis SE, Kazazian HH, Housman DE, Pulver AE, 1998, Identification of sequence variants and analysis of the role of the catechol-Omethyltransferase gene in schizophrenia susceptibility. Biol Psychiatry 43, 425–431. [3] Strous RD, Bark N, Woerner M, Lachman HM, 1997 Lack of association of a functional catechol-O-methyltransferase gene polymorphism in schizophrenia. Biol Psychiatry 41, 493–495.
P.1.a.014 No association of CCK promoter gene −36C>T polymorphism and panic disorder in the Korean population
S235
attack scores during the previous one month, as well as scores for anticipatory anxiety, panic distress, and agoraphobic distress, as determined by a visual analogue scale (VAS). And all the subjects were recommended to complete the measures such as STAI-S, STAI-T, BDI, SCL-90-R, ASI-R, CGI-S, PDSS, and (HAMD). Responder analyses were conducted on the basis of changes in CGI-I scores after 10 weeks of treatment. Results: The distribution of genotype is within the range of Hardy-Weinberg equilibrium in both panic group and control. Genotype and allele distribution of CCK promoter −36C>T polymorphism patients with panic disorder was not significantly different from those of the controls. In addition, after excluding panic disorder patients with major depressive disorder, we did not find out the association of CCK −36C>T with the panic disorder without comorbidities. In analysis for determine the difference of 10 week-pharmacotherapeutic response according to genotype, CGI-I scores did not significantly differ among the genotypes of CCK promoter −36C>T polymorphism. When we subdivided the patients into responders (CGI-I: 1−2) and non-responders (CGI-I: 3−7), we found no differences between the groups with regard to genotypic and allelic frequencies. Conclusion: This study suggested that the CCK promoter −36C>T polymorphism may have not a potential role for susceptibility to panic disorder in the Korean population. And the response to 10 week-pharmacotherapy is not different according to the genotype of CCK promoter −36C>T polymorphism. Thus calls for consecutive studies in order to pile up the data with larger different ethnic background. References [1] Wang Z, Valdes J, Noyes R, Zoega T, Crowe RR, 1998, Possible association of a cholecystokinin promoter polymorphism (CCK-36CT) with panic disorder. Am J Med Genet (Neuropshchiatr Genet) 81, 228– 234. [2] Kennedy JL, Bradwejn J, Koszychi D, King N, Crowe R, Vincent J, et al, 1999, Investigation of cholecystokinin system genes in panic disorder. Mol Psychiatry 4, 284–285.
W. Kim ° , J.M. Woo. Seoul Paik Hospital, Department of Psychiatry, Seoul, South-Korea Objective: Panic disorder is a common anxiety disorder with a lifetime prevalence of 1−3%, and characterized as many somatic symptoms combined with severe anxiety, including fears of going crazy or dying. There were researches about the biological basis of panic disorder, which suggested some physiological factors are closely related with panic attack or susceptibility of anxiety. Lactate infusion, m-chlorophenylpiperazine infusion, tryptophan depletion and cholecystokinin infusion is known to induce anxiety. Among these, cholecyctokinin (CCK), peptide located mainly in brain and digestive system, is reported to have interactions with dopamine and related with various physiologic properties such as anxiety, appetite, respiration, sleep. Some genetic polymorphisms of these anxiety-related physiologic agents have been reported to related with panic disorder. Recently, possible association of CCK promoter gene −36C>T was reported in Caucasian. Therefore, we aimed to test the possible association between cholecystokinin(CCK) promoter gene −36C>T polymorphism and panic disorder in Korean population. Methods: 267 patients with panic disorder and 82 healthy controls participated in this study. Genotyping was performed by polymerase chain reaction-based method. Chip-based MALDITOF (matrix assisted laser desorption ionization time of flight) mass spectrometry platform was applied in analysis. The severity of the patients’ panic disorders was assessed according to panic
P.1.a.015 Neuregulin-1 risk haplotype and eye movements in schizophrenia M. Haraldsson1 ° , U. Ettinger2 , B.B. Magnusdottir1 , T. Sigmundsson1 , E. Sigurdsson1 , H. Petursson1 . 1 LandspitaliUniversity Hospital, Psychiatry, Reykjavik, Iceland; 2 Institute of Psychiatry, Center for Neuroimaging Sciences, London, United Kingdom Aim: To investigate effects of the Neuregulin-1 (NRG-1) “atrisk” haplotype on antisaccade (AS) and smooth pursuit (SP) eye movements in schizophrenia patients and healthy controls. Background: Recent studies provide evidence for an association between variations in the NRG-1 gene and schizophrenia (Stefansson et al. 2002). NRG-1 has multiple roles in the central nervous system including neuronal migration, synapse formation and expression of the NMDA glutamate receptor. The phenotypic heterogeneity of schizophrenia complicates studies of how NRG-1 and other potential risk genotypes affect the disease phenotype. This problem may be circumvented by studying endophenotypes. Endophenotypes are biological or behavioural features which may be more closely related to underlying disease genes than the complex clinical phenotype (Braff et al. 2007). Deficits in AS and SP eye movements are promising endophenotypes in genetic studies