基于影像遗传的精神分裂症抗精神病药物疗效的预测研究

精神分裂症(SCZ)是常见重性精神疾病，抗精神病药物(APD)治疗为主，但疗效存在个体差异，显著影响治疗依从性及预后。申请人课题组前期开发的纹状体功能异常的个体化影像诊疗标记，全基因组水平发现的APD非多巴胺受体拮抗作用疗效新靶点，共同提示个体化的影像、遗传特征可能与APD疗效异质性关联。本项目拟基于前期工作基础，建立SCZ单一种类、不同受体作用机制常用APD治疗规范化临床研究队列，整合前期积累的SCZ药物治疗样本资源，建立并维护SCZ影像遗传多维度指标数据库；开展个体化影像遗传特征提取的方法学探索，研究多模态数据融合的机器学习方法；构建并优化基于影像遗传的SCZ抗精神病药物疗效的个体化评估预测模型，并基于空间相关探寻APD疗效预测影像遗传标记的生物机制。预期结果可作为SCZ个体化治疗药物选择的依据，有望促进症状早期控制、增加治疗依从性、改善疾病预后，为APD疗效机制提供客观的科学依据。

Schizophrenia is a common severe mental disease. Antipsychotic drugs are effective treatments but are ineffective for some patients, which is associated with nonadherence in patients and significantly affects prognosis. In our previous studies, a new neuroimaging biomarker based on the functional striatal abnormalities (FSA) has been established the utility in predicting antipsychotic treatment response in schizophrenia, and genes related to synaptic function, neurotransmitter receptors, and schizophrenia risk have been identified associated with response to antipsychotics. The FSA neuroimaging biomarker and the new targets of the antipsychotic drugs for the non-dopamine receptor antagonistic effect suggest that the individualized imaging genetic characteristics may be related to the heterogeneity of response to antipsychotics. Based on the previous work, the research work to be carried out in this project includes: 1) establish a standardized clinical study cohort of schizophrenia with monotherapy of antipsychotics for different receptor mechanisms, and establish and maintain a multi-dimensional imaging genetic database of schizophrenia; 2) carry out the methodological exploration of individualized neuroimaging and genetic features extraction and study the machine learning method of multi-mode data fusion; 3) develop an optimized individualized evaluation and prediction model of response to antipsychotic drugs based on neuroimaging and genetic features, and explore the biological mechanism of the identified imaging genetic index based on spatial correlation analysis. The expected results will provide support for the clinical decision of individualized antipsychotic drugs for patients with schizophrenia and suggest the evidence for the mechanism underlying the antipsychotics response, which will contribute to the early controlling of symptoms, increasing treatment adherence and improving the prognosis of schizophrenia.