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疾病，是全球年轻人残疾调整寿命年的第八大原因。多巴胺2受体阻滞剂-唯一可用于治疗精神分裂症的药物类别-在大约70%的患者中减少精神病，但它们不能实质性地改善认知和动机缺陷。广泛的临床前和临床证据指出NMDA受体作为替代治疗靶点，但尚不清楚优先位于兴奋性或抑制性细胞上的受体亚型是否更功能失调。我们将使用脑磁图（MEG）数据的动态因果模型来研究相互作用的兴奋性和抑制性细胞（dys）功能如何有助于精神分裂症的精神病症状以及认知和动机障碍。希望这将有助于为药物治疗选择提供信息，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.