DNA methylation of membrane-bound catechol-O-methyltransferase in Malaysian schizophrenia patients.

AIM: This study examined catechol-O-methyltransferase (COMT) DNA methylation in the peripheral blood of schizophrenia patients and also in healthy controls to investigate its potential use as a peripheral biomarker of schizophrenia and its relations with the clinical variables of schizophrenia patients. METHODS: We examined the DNA methylation levels of COMT using genomic DNA from the peripheral blood of schizophrenia patients (n = 138) and healthy control participants (n = 132); all were Malaysian Malays. The extracted DNA was bisulfite converted, and the percentage methylation ratio value was calculated based on the results following a MethyLight protocol analysis. RESULTS: The percentage methylation ratio of COMT was lower in schizophrenia than it was in the healthy controls (P < 0.001) and was different between the body mass index (P = 0.003) and antipsychotic (P = 0.004) groups. The COMT DNA methylation rate was lower in patients receiving atypical antipsychotics (P = 0.004) and risperidone (P = 0.049) as compared to typical antipsychotics. The Excitement and Depressed subdomains of the Positive and Negative Syndrome Scale were inversely related (P < 0.001) and therefore predictors (Excitement: b = -11.396, t = -4.760, P < 0.001; Depressed: b = -7.789, t = -3.487, P = 0.001) of COMT DNA methylation. CONCLUSION: Our results suggested that the methylation level was affected by the severity of the clinical symptoms of schizophrenia and might also be influenced by pharmacological treatment. The epigenetic alteration of COMT in the peripheral blood could be a potential peripheral biomarker of schizophrenia.

Reelin (RELN) DNA methylation in the peripheral blood of schizophrenia.

The epigenetic changes of RELN that are involved in the development of dopaminergic neurons may fit the developmental theory of schizophrenia. However, evidence regarding the association of RELN DNA methylation with schizophrenia is far from sufficient, as studies have only been conducted on a few limited brain samples. As DNA methylation in the peripheral blood may mirror the changes taking place in the brain, the use of peripheral blood for a DNA methylation study in schizophrenia is feasible due to the scarcity of brain samples. Therefore, the aim of our study was to examine the relationship of DNA methylation levels of RELN promoters with schizophrenia using genomic DNA derived from the peripheral blood of patients with the disorder. The case control studies consisted of 110 schizophrenia participants and 122 healthy controls who had been recruited from the same district. After bisufhite conversion, the methylation levels of the DNA samples were calculated based on their differences of the Cq values assayed using the highly sensitive real-time MethyLight TaqMan® procedure. A significantly higher level of methylation of the RELN promoter was found in patients with schizophrenia compared to controls (p = 0.005) and also in males compared with females (p = 0.004). Subsequently, the RELN expression of the methylated group was 25 fold less than that of the non-methylated group. Based upon the assumption of parallel methylation changes in the brain and peripheral blood, we concluded that RELN DNA methylation might contribute to the pathogenesis of schizophrenia. However, the definite effects of methylation on RELN function during development and also in adult life still require further elaboration.

Disrupted-in-Schizophrenia-1 SNPs and Susceptibility to Schizophrenia: Evidence from Malaysia.

OBJECTIVE: Even though the role of the DICS1 gene as a risk factor for schizophrenia is still unclear, there is substantial evidence from functional and cell biology studies that supports the connection of the gene with schizophrenia. The studies associating the DISC1 gene with schizophrenia in Asian populations are limited to East-Asian populations. Our study examined several DISC1 markers of schizophrenia that were identified in the Caucasian and East-Asian populations in Malaysia and assessed the role of rs2509382, which is located at 11q14.3, the mutual translocation region of the famous DISC1 translocation [t (1; 11) (p42.1; q14.3)]. METHODS: We genotyped eleven single-neucleotide polymorphism (SNPs) within or related to DISC1 (rs821597, rs821616, rs4658971, rs1538979, rs843979, rs2812385, rs1407599, rs4658890, and rs2509382) using the PCR-RFLP methods. RESULTS: In all, there were 575 participants (225 schizophrenic patients and 350 healthy controls) of either Malay or Chinese ethnicity. The case-control analyses found two SNPs that were associated with schizophrenia [rs4658971 (p=0.030; OR=1.43 (1.35-1.99) and rs1538979-(p=0.036; OR=1.35 (1.02-1.80)] and rs2509382-susceptibility among the males schizophrenics [p=0.0082; OR=2.16 (1.22-3.81)]. This is similar to the meta-analysis findings for the Caucasian populations. CONCLUSION: The study supports the notion that the DISC1 gene is a marker of schizophrenia susceptibility and that rs2509382 in the mutual DISC1 translocation region is a susceptibility marker for schizophrenia among males in Malaysia. However, the finding of the study is limited due to possible genetic stratification and the small sample size.

Relationship of psychological symptoms, antipsychotics and social data with psychosocial function in schizophrenia patients in Malaysia.

INTRODUCTION: The present study investigated the relationship between psychological symptoms and psychosocial function and the role of relevant sociodemographic data and antipsychotic use in the prediction of psychosocial function among multiracial schizophrenia outpatients in Malaysia. METHODS: A total of 223 participants were recruited in this cross-sectional study conducted from December 2010 to April 2011. Psychological symptoms were assessed using the Positive and Negative Syndrome Scale whilst the psychosocial function was assessed using the Personal and Social Performance scale. Sociodemographic and treatment variables were gathered through interview or review of the medical records. RESULTS: All dimensions of psychosocial functions were inversely correlated with Positive and Negative Syndrome Scale sub-domains. Only the disorganization sub-domain significantly predicts all dimensions of psychosocial function. For social data, body mass index and employment status were significant predictors of all dimensions of psychosocial functions. Typical antipsychotics significantly predict social function negatively as compared to sulpiride (ß = -0.152, P = 0.028). DISCUSSION: We found that the relationship between psychological symptoms and psychosocial functions were relatively consistent with the findings from the Caucasian population. Additionally, disorganization was the only significant predictor of all dimensions of psychosocial functions. This further emphasized the importance of cognition in psychosocial function. The roles of sulpiride, body mass index and employment status as predictors of psychosocial function were also discussed.

Concurrent Validity Of The Depression And Anxiety Components In The Bahasa Malaysia Version of The Depression Anxiety and Stress Scales (DASS)

Scales 21-item (DASS-21) has been widely used ever since the establishment of its validity. To consolidate the evidence of the BM DASS-21 validity by examining its concurrent validity. Methods: The BM DASS was administered together with the Hospital Anxiety and Depressive Scale (HADS) to a total of 246 patients at International Islamic University Malaysia (IIUM) Infertility Centre. Results: The anxiety domain of BM DASS-21 had good correlation with anxiety domain in HADS (0.61) but for DASS depressive domain, it had modest correlation with its respective domain in HADS (0.49). Conclusions: The results of this study further ensconced the evidence that the BM DASS-21 had relatively satisfactory psychometric properties for clinical subjects in Malaysia.