工作记忆缺损是精神分裂症认知功能障碍的核心症状之一。我们在前临床研究中发现突触可塑性下降是引起工作记忆缺损的细胞机制，我们的临床研究结果表明ANK3基因是影响精神分裂症工作记忆缺损的重要易感基因。因此，本课题提出ANK3基因可能通过影响突触可塑性调控精神分裂症工作记忆缺损。为了验证此假设，首先，本课题将通过12周奥氮平治疗首发精神分裂症患者的随访研究，探索奥氮平治疗精神分裂症患者工作记忆缺损过程中ANK3基因的变化情况，在分子水平上明确ANK3基因与疗效的关系。其次，本课题将在已建立的精神分裂症动物模型药理学研究范式基础上，探讨ANK3基因在海马、前额叶突触可塑性中的作用；以及ANK3基因是否通过调控AMPA受体表达，影响突触可塑性变化。本研究不仅帮助我们在现有研究基础上更好地理解ANK3基因在精神分裂症工作记忆缺损病理过程中的作用，而且将为研发新型抗精神病药物提供新的理论依据和实践经验。

Working memory defict is one of the core cognitive symptoms in schizophrenia. Our previous preclinical study showed that decreased synaptic plasticity is the celluar mechanism of working memory deficit. Our clinical work showed that ANK3 is an important susceptiblity gene in working memory deficit. Therefore, we hypothesized that ANK3 may play a regulatory role in working memory deficit via influncing synaptic plasticity. In order to verify the hypothesis, we first aim to conduct a longitudinal study to investigate the changes of working memory performance and ANK3 expression and clarify the relationship between ANK3 gene and therapeutic effect at the molecular level. Second, we aim to investigate the role of ANK3 in synaptic plasticity of prefrontal cortex, and investigate whether ANK3 influence synaptic plasticity via regulating AMPA receptors, based on the schizophrenia-like animal model. This study will help us understand the pathogenic mechanism of ANK3 gene in schizophrenic cognitive impairment and provide theory evidence and practical experience for the development of new antipsychotics.