Poster #108 THE INFLUENCE OF DISC1 SER704CYS POLYMORPHISM ON THE CORTICAL THICKNESS OF SALIENCE NETWORK (INSULA AND ANTERIOR CINGULATE) IN PSYCHOSIS

Abstract

s of the 3rd Biennial Schizophrenia International Research Conference / Schizophrenia Research 136, Supplement 1 (2012) S1–S375 S319 Poster #107 EVIDENCE OF AN ASSOCIATION BETWEEN DYSBINDIN GENE AND AGE AT ONSET IN SCHIZOPHRENIA Kyuyoung Lee1, Eunjeong Joo1, Yongsik Kim2 1Department of Neuropsychiatry, Eulji University School of Medicine, Eulji General Hospital, Seoul, Korea; 2Department of Psychiatry & Behavioral Science and Institute of Human Behavioral Medicine, Seoul National University College of Medicine, Seoul, Korea Background: The dysbindin gene (DTNBP1) is located in chromosome 6p22.3, one of the regions of positive linkage for schizophrenia. In particular, dysbindin protein has been found to play a role in the glutatmate neural transmission in the brain. A strong genetic association between DTNBP1 and schizophrenia has been replicated through many recent studies. However, we have not replicated positive association between DTNBP1 and schizophrenia in our Korean sample. Because schizophrenia has been regarded as a disease with a quite heterogeneous origin and evolvement, it is useful to categorize patients with schizophrenia into relatively homogeneous subsets based on clinical characteristics including age at onset (AAO). Therefore, we investigated the association between DTNBP1 and AAOof schizophrenia. Methods: We assessed age at first occurrence of positive psychotic symptomsof 197 patients with schizophrenia. Four SNPs, SNPA, P1763, P1320 and P1655 of DTNBP1 were genotyped. Results: In SNPA, the patients with AT (N=10) showed significant earlier AAO than those with AA (N=187) (p<0.0001). The patients with heterozygote for SNP P1763 (TG, N=40) or P1320 (CT, N=41) also showed significant earlier AAO than those with homozygote (P<0.0001, P<0.0001, respectively). However, in SNP P1655, there was no significant difference of AAO between genotypes. Discussion: In conclusion, although we were unable to support an association between DTNBP1 and schizophrenia, DTNBP1 might play a role in disease-modifying. However, considering the several limitations of this study, further research involving different polymorphisms in DTNBP1and various clinical subsets with sufficient numbers will be required to evaluate the contribution of DTNBP1 to schizophrenia. Poster #108 THE INFLUENCE OF DISC1 SER704CYS POLYMORPHISM ON THE CORTICAL THICKNESS OF SALIENCE NETWORK (INSULA AND ANTERIOR CINGULATE) IN PSYCHOSIS Lena Palaniyappan1, Vijender Balain1, Molly Simmonite1, Liam Carrol2, Peter McGuffin2, Katherine Aitchison2, Peter F. Liddle1 1Division of Psychiatry, University of Nottingham, Nottingham, England, United Kingdom; 2MRC SGDP, Institute of Psychiatry, Kings College, London, England, United Kingdom Background: Psychosis is characterized by significant reduction of grey matter in anterior cingulate cortex (ACC) and the insula. An emerging literature has demonstrated an association between the Disrupted-inSchizophrenia 1 (DISC1) gene and the development of cortical grey matter. Allelic variation at rs821616 (Ser704cys) has been associated with both structural and functional changes in psychosis. Our objective was to examine the relationship between grey matter reduction salience network sites (ACC/Insula) and Ser704cys variation in psychosis. Methods: High-resolution anatomical scans were obtained from 45 subjects (23 with psychosis and 22 healthy individuals with 10 cysteine carriers in each group). We employed cortical surface based analysis using Freesurfer (v5.0) to measure cortical thickness and surface area. Various cortical regions were parcellated using Destrieux atlas, and the regions constituting the insula (short and long gyri) and anterior cingulate were included for further analysis. Results: We detected a significant omnibus interaction effect between diagnostic status and genotype for cortical thickness (F(1,38)=5.071, p=0.03). Among cysteine non-carriers, a highly pronounced diagnostic difference was noted in the adjusted mean thickness (patients = 3.014mm, controls = 3.254mm, t=3.54, p=0.002). Such a diagnostic difference was not noted in cysteine carriers (patients = 3.122mm, controls = 3.139mm, t=0.23, p=0.83). Among patients, a significant difference was also noted between the two genetic groups in terms of levels of functioning measured using Social and Occupational Functioning Scale (total SOFAS score: cys non-carriers = 47.54; carriers = 59.10, F=6.07, p=0.02) and symptom burden measured using Signs and Symptoms in Psychotic Illness scale (total SSPI score: cys non-carriers = 13.46; carriers = 8.10, F=2.71, p=0.11). The polymorphism was not associated with effects on the cortical surface area of ACC/Insula. Discussion: Our findings suggest that morphometric changes associated with psychosis are influenced by the polymorphic variation in DISC1, which plays a cardinal role in regulating neuronal migration. The pathoplastic effect of DISC1 in psychosis is likely to be mediated by the structure of grey matter in the Salience Network. Poster #109 HISTORICAL STUDY OF INFLUENCE OF NON-GENETIC FACTORS ON TWIN CONCORDANCE FOR SCHIZOPHRENIA