Introduction: Significant evidences from functional studies have shown that DISC1 gene has a role in the pathogenesis of schizophrenia, although the basis of the genetic defect has yet to be established. There has been a shift of emphasis from DISC1 gene variations to other types of genetic defects namely copy number and epigenetic, both of which have not been well investigated. Thus, the aim of this study is to examine the DNA methylation status of DISC1 gene in patients with schizophrenia. Methods: In this study, 239 subjects were included, 117 schizophrenia patients and 122 healthy controls. Genomic DNA was derived from peripheral blood and bisulfite converted. The DNA methylation level was quantitatively measured by Methylight Taqman analysis. Sociodemographic and the clinical parameters were noted. The severity of the clinical symptoms was assessed using Positive and Negative Syndrome Scale (PANSS). Results: The mean age and gender distribution between the study groups were similar. There was no significant difference in the methylation level of DISC1 between the patients and control group. When patients were compared by age, duration of illness, age at diagnosis, body mass index, smoking status, PANSS score and types of antipsychotic treatment, the DNA methylation level of DISC1, did not show any significant difference (p>0.05). Conclusions: This study found no significant difference in methylation level of DISC1 gene between schizophrenia patients and healthy control. Therefore, it is suggested that aberrant DNA methylation of DISC1 most probably does not contribute to the pathogenesis of schizophrenia.

Introduction: The dopamine hypothesis has earlier dominated the theories for the development of schizophrenia based on the early pharmacologic evidence. The antipsychotic drugs, among others, is thought to interfere with the function of the dopamine D2 receptor (DRD2) resulting in clinical improvement. Accumulating evidence suggest the role of epigenetic mechanisms in the pathophysiology of schizophrenia. Despite this, specific evidence linking the DRD2 DNA methylation with schizophrenia is insufficient mainly due to the poor accessibility and limited brain samples. Of late, new data has suggested the global impact of DNA methylation in the development of schizophrenia, thus methylation in the peripheral blood could infer changes in the brain. The aim of this study was to assess the DRD2 DNA methylation in the peripheral blood of schizophrenia. Materials and method: The case control study consisted of 138 schizophrenia patients and 132 healthy controls. The genomic DNA from the peripheral blood was bisulfite converted. The DRD2 DNA methylation level was quantitatively measured by using the MethyLight Taqman® assay and normalized with the ALU reference control to give the percentage methylation ratio. The demographic data was calculated using descriptive statistics while parametric variables were compared using independent samples t-test or analysis of covariance. Results: There was a significant hypomethylation of DRD2 in schizophrenia compared to the control group (p=0.001). The hypomethylation was also significant in males (p=0.007) and females (p=0.036) patients. Conclusion: This study supports the possible role of DNA methylation of DRD2 gene could contribute to the pathogenesis of schizophrenia.

Introduction: The dopamine hypothesis of schizophrenia is based on the fact that hyperdopaminergic state is involved in causing psychosis and antipsychotic drugs block the dopamine receptor. COMT regulates the homeostatic levels of neurotransmitter dopamine in the synapses and plays a role in the neurocognitive function. The dysregulation of dopamine in the prefrontal cortex influences the cognitive function and the severity of the psychotic symptoms in schizophrenia. During epigenetic event, methylated COMT gene may cause reduction in its expression and contribute to the clinical presentation of schizophrenia. Therefore, the aim of this study was to assess the feasibility of using COMT DNA methylation for the prediction of specific psychotic presentation of schizophrenia. Materials and method: In this study, 138 schizophrenia patients were recruited from the Psychiatry Clinic, Hospital Tengku Ampuan Afzan, Kuantan Pahang. Genomic DNA from peripheral blood was subjected to the Methylight Taqman® analysis for quantitative measurement of the COMT DNA methylation. The psychopathological symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). Results: The regression analysis showed that the Positive and Excited subdomains of PANSS were significant predictors of COMT hypomethylation (β= -0.288, p= -0.031; β= - 0.288, p= -0.031). The Excited subdomain of PANSS was negatively correlated with COMT DNA methylation (r 2 = -0.380, p= 0.000) as well as the Depressed subdomain (r 2 = -0.288, p= 0.001). Conclusion: The relationship between DNA methylation of COMT with the positive, excited and depressed symptoms might indicate the epigenetic role of COMT gene in the manifestation of schizophrenia.