静息态皮层-纹状体功能连接在抗精神病药物治疗应答中的作用研究

项目名称： 静息态皮层-纹状体功能连接在抗精神病药物治疗应答中的作用研究

项目编号： No.81501158

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 李鹏

作者单位： 北京大学

项目金额： 19万元

中文摘要： 精神分裂症是一种常见精神疾病，致残率极高。目前，抗精神病药物是治疗精神分裂症的主要方法，但不同药物的临床反应存在很大差异，约有1/4的患者产生不同程度的药物抵抗，关键原因在于通过临床症状改善程度来评估药物治疗应答存在明显的滞后性，并不能在药物使用早期阶段判断药物疗效。因此亟需探索治疗早期阶段脑网络表征的改变，找寻预测抗精神病药物治疗应答的生物学标记。我们的前期研究发现，精神分裂症患者存在广泛的皮层-纹状体环路连接异常，而有效的抗精神病治疗可以改变皮层-纹状体的功能连接模式，但药物治疗早期皮层-纹状体环路是否发生改变以及该变化是否能够预测抗精神病药物治疗应答尚不清楚。因此，本课题拟通过神经影像学、分子遗传学和神经药理学等技术方法探索静息态皮层-纹状体功能连接在抗精神病药物治疗应答中的作用，发现可用于判断治疗应答的生物学标记，以期实现合理选择药物、减少药物抵抗以及改善预后的最终目的。

中文关键词： 精神分裂症；脑网络；抗精神病药物；基因多态性；生物标记

英文摘要： Schizophrenia is a severe, disabling, and highly heritable psychiatric disorder of unknown etiology. Clinically, antipsychotic drugs are standard therapy, but the clinical response is variable and currently unpredictable. Each year, one fourth of all patients are switched to a different antipsychotic in an effort to better manage their illness. The crucial reason is that an adequate medication trial requires at least 4 weeks of treatment at a therapeutic dose before lack of clinical response can be confirmed. Therefore, there is a clear clinical need for a biomarker to assist with the determination of drug effectiveness early in the course of treatment, or before medication is initiated. Our previous studies have showed that schizophrenia was characterized in part by abnormalities in the neural activity and functional connectivity within the cortico-striatal system. Additionally, we also found the antipsychotic effects of electroconvulsive therapy might result from the modulation of cortico-striatal activity. However, if the modulation of connectivity patterns in early course of treatment could be an indicator for good treatment remains unknown. In the present project, we will combine functional magnetic resonance imaging (fMRI), molecular genetics, and neuropharmacology to elucidate the role of resting-state cortico-striatal connectivity in the response to antipsychotic medication in schizophrenia. Our aim is to find a potential biomarker to predict the outcome of antipsychotic medication.

英文关键词： schizophrenia;brain network;antipsychotics;gene polymorphism;clinical response