Using computational modelling to investigate excitatory and inhibitory cell dysfunction in schizophrenia

精神分裂症是一种严重的精神障碍，是全世界年轻人残疾调整寿命的第八大原因。多巴胺2受体阻滞剂是治疗精神分裂症的唯一药物类别，可减少约70%患者的精神病，但它们未能显著改善认知和动机缺陷。广泛的临床前和临床证据表明，NMDA受体是一种替代的治疗靶点，但目前尚不清楚优先位于兴奋性细胞或抑制性细胞上的受体亚型是否更具功能障碍。我们将使用脑磁图(MEG)数据的动态因果建模来研究相互作用的兴奋和抑制细胞(Dys)功能如何导致精神分裂症的精神病症状以及认知和动机障碍。希望这将有助于指导谷氨酸能治疗的选择，并指导未来的药物开发。

Schizophrenia is a severe psychiatric disorder and the eighth highest cause of disability-adjusted life years in young adults worldwide. Dopamine 2 receptor blockers - the only drug class available for the treatment of schizophrenia - decrease psychosis in around 70% patients, but they fail to substantially improve cognitive and motivational deficits. Extensive pre-clinical and clinical evidence points to NMDA receptors as an alternative therapeutic target, but it is unclear whether receptor subtypes located preferentially on excitatory or inhibitory cells are more dysfunctional. We will use dynamic causal modeling of magnetoencephalography (MEG) data to investigate how interacting excitatory and inhibitory cell (dys)function contributes to psychotic symptoms as well as cognitive and motivational impairments in schizophrenia. It is hoped that this will help inform glutamatergic treatment selection and guide future drug development.