首发未服药精神分裂症患者治疗前后脑影像及DNA甲基化与基因表达研究

精神分裂症累及约1%人群并致其残疾，且具体病因及病理机制至今未明。通过他人和本课题组对早发、晚发及慢性分裂症的脑影像研究可观察到某些脑结构和功能的改变，这种改变多由某些基因表达异常所引起的蛋白质和酶的功能缺陷所致。抗精神病药的作用机制一方面是阻断神经递质受体，影响某些信号通路，更重要的可能是影响基因表达，而DNA甲基化是调节基因表达的最主要途径之一。但药物影响哪些基因位点的甲基化进而影响基因表达和相关酶、蛋白质的功能，引起脑结构和功能改变并最终改善精神病性症状，尚不明了。我们试图通过观察单一抗精神病药治疗前后全基因组甲基化的改变（我们在小样本试验时已观察到这种改变）和相应基因的表达变化，以及治疗前后脑结构和脑功能的改变，首次全面系统了解抗精神病药治疗的基因组甲基化效应；发现相关的药物效应基因；了解药物对脑结构和功能的影响。也将使我们更深入地理解抗精神病药作用机制以及分裂症本身的病理机制。

Schizophrenia is a chronic, disabling mental disorder found in about 1% of the general population. However, the detailed etiology and pathologic mechanism of schizophrenia is still largely unknown. In our previous MRI studies in early-onset, late-onset, and chronic schizophrenia, we observed structural and/or functional impairments in several brain regions. We therefore hypothesized that structural and/or functional changes in the brain of schizophrenic patients may be induced by aberrant genes expression Antipsychotic drugs may exert their roles through blocking dopamine and/or serotonin receptors in the brain. More importantly, antipsychotic drugs may influence DNA methylation and gene expression. In our small preliminary study, we have already found noticeable differences in the methylation status of several genes after antipsychotic treatments. In this study, we proposed to explore the effect of short term antipsychotic drug use on DNA methylation, gene expression, structural and functional alterations in the brain, and finally identifying treatment related genes. This study will examine the effect of antipsychotic drugs on global DNA methylation in genomic DNA. This will help us to understand the mechanism involved in antipsychotic treatments and pathogenesis of schizophrenia.