Functional characterization of two variants in the 3'-untranslated region (UTR) of transcription factor 4 gene and their association with schizophrenia in sib-pairs from multiplex families.

Transcription factor 4 (TCF4) gene plays an important role in nervous system development and it always associated with the risk of schizophrenia. Since miRNAs regulate targetgenes by binding to 3'UTRs of target mRNAs, the functional variants located in 3'UTR of TCF4 are highly suggested to affect the gene expressions in schizophrenia. To test the hypothesis regarding the effects of the variants located in 3'UTR of TCF4, we conducted an in silico analysis to identify the functional variants and their predicted functions. In this study, we sequenced the 3'UTR of TCF4 in 13 multiplex schizophrenia families and 14 control families. We found two functional variants carried by three unrelated patients. We determined that the C allele of rs1272363 and the TC insert of rs373174214 might suppress post- transcriptional expression. Secondly, we cloned the region that flanked these two variants into a dual luciferase reporter system and compared the luciferase activities between the pmirGLO-TCF4 (control), pmirGLO-TCF4-rs373174214 and pmirGLO-TCF4-rs1273263. Both pmirGLO-TCF4-rs373174214 and pmirGLO-TCF4-rs1273263 caused lower reporter gene activities, as compared to the control. However, only the C allele of rs1272363 reduced the luciferase activity significantly (p = 0.0231). Our results suggested that rs1273263 is a potential regulator of TCF4 expression, and might be associated with schizophrenia.

Association of social support and quality of life among people with schizophrenia receiving community psychiatric service: A cross-sectional study.

OBJECTIVE: To understand the needs of patients with schizophrenia for recovery, this study examined the type and level of social support and its association with quality of life (QOL) among this group of patients in the city of Kuala Lumpur. METHOD: A cross-sectional study was conducted on 160 individuals with schizophrenia receiving community psychiatric services in Hospital Kuala Lumpur (HKL). The WHOQOL-BREF, Brief Psychiatric Rating Scale (BPRS) and Multidimensional Scale of Perceived Social Support (MSPSS) were used to assess QOL, severity of symptoms and social support, respectively. The study respondents were predominantly Malay, aged less than 40, males, single, unmarried, had lower education levels and unemployed. RESULTS: About 72% of the respondents had poor perceived social support, with support from significant others being the lowest, followed by friends and family. From multiple regression analysis, social support (total, friend and family) significantly predicted better QOL in all domains; [B=0.315 (p<0.001), B=0.670 (p<0.001), B=0.257 (p<0.031)] respectively in Physical Domain; [B=0.491 (p<0.001), B=0.735 (p<0.001), B=0.631 (p<0.001)] in Psychological Domain; [B=1.065 (p<0.001), B=0.670 (p<0.017), B=2.076 (p<0.001)] in Social Domain and; [B=0.652 (p<0.001), B=1.199 (p<0.001), B=0.678 (p<0.001)] in Environmental Domain. Being married and having shorter duration of illness, lower BPRS (total) scores, female gender and smoking, were also found to significantly predict higher QOL. CONCLUSION: Social support is an important missing component among people with schizophrenia who are already receiving formal psychiatric services in Malaysia.

Metabolic syndrome and cardiovascular risk among patients with schizophrenia receiving antipsychotics in Malaysia.

INTRODUCTION: This study aimed to determine the prevalence of metabolic syndrome and risk of coronary heart disease (CHD) in patients with schizophrenia receiving antipsychotics in Malaysia. METHODS: This cross-sectional study, conducted at multiple centres, involved 270 patients who fulfilled the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV-TR diagnostic criteria for schizophrenia, were on antipsychotic medications for at least one year, and were screened for metabolic syndrome. Patients receiving mood stabilisers were excluded. Metabolic syndrome was defined according to the National Cholesterol Education Program ATP III criteria modified for Asian waist circumference. Risk for cardiovascular disease was assessed by using Framingham function (all ten-year CHD events). RESULTS: The prevalence of metabolic syndrome was 46.7% (126/270). Among all the antipsychotics used, atypical antipsychotics (monotherapy) were most commonly used in both the metabolic and non-metabolic syndrome groups (50.8% vs. 58.3%). The ten-year risk for CHD was significantly higher in patients with metabolic syndrome. The proportion of patients with high/very high risk for CHD (Framingham ≥ 10%) was greater in patients with metabolic syndrome than in those with non-metabolic syndrome (31.5% vs. 11.0%, odds ratio 3.9, 95% confidence interval 2.0-7.6; p < 0.001). The mean body mass index was higher in patients with metabolic syndrome than in those without (29.4 ± 5.1 kg/m2 vs. 25.0 ± 5.6 kg/m2; p < 0.001). CONCLUSION: Patients with schizophrenia receiving antipsychotics in Malaysia have a very high incidence of metabolic syndrome and increased cardiovascular risk. Urgent interventions are needed to combat these problems in patients.