研究指出脑发育过程中多巴胺成熟异常进而影响工作记忆，是精神分裂症发病机制之一；COMT与BDNF作为精神分裂症的风险基因，其基因多态性通过调控多巴胺浓度影响工作记忆,然而COMT与BDNF基因多态性在精神分裂症患者工作记忆损害中的神经调控机制及交互作用机制目前尚不清晰。本课题前期研究发现COMT与BDNF基因多态性在前额叶存在功能连接密度上的交互作用，并与多巴胺倒U调控模型存在关联性。因此本课题拟采用多模态MRI技术，研究COMT与BDNF基因多态性在健康人群及精神分裂症患者中对工作记忆的调控机制、调控模式及基因间的交互调控作用机制，探索基因遗传、脑结构和功能连接改变与工作记忆损害的关系，并力图阐明工作记忆的遗传-脑-行为学通路。本研究有助于建立COMT、BDNF风险基因型造成工作记忆紊乱的神经机制，为精神分裂症的早期预防及靶基因治疗提供可靠依据。

Many studies suggested that one of the important mechanisms of schizophrenia is that the abnormities dopamine maturate during brain development result in further abnormality process of working memory; COMT and BDNF , as the risk genes of schizophrenia, were founded influence working memory by dopamine regulation. Now the mechanism and interaction mechanism that how COMT and BDNF influence the working memory in both healthy people and schizophrenia patients is not clear. We have found the significant interaction on prefrontal cortex between COMT rs4680 and BDNF rs6265 on functional connectivity density in the early research, which was associated with inverted U-shaped modulation by dopamine signaling. The present study, aiming at normal subjects and schizophrenia patients, will explore the modulation mechanism and also interaction mechanism that how the COMT and BDNF polymorphism mediate working memory using MRI. This study further intends to investigate the modulatory effect of genetic polymorphisms on brain structural and functional connectivity, and their relationship with working memory, and try to give the details of gene-brain-working memory pathway.The present study can help to understand the neural mechanism of COMT and BDNF risk variants leading to working memory impairment, and provide the theoretical basis for the early prevention of schizophrenia, and also for the new target gene development and therapy.