甲基苯丙胺所致精神病与精神分裂症鉴别诊断生物标记系统的建立与运用

This project focuses on the dispute on the judicial identification of criminal responsibility and differential diagnosis of methamphetamine-associated psychosis (MAP) and schizophrenia (SCZ). According to the evidence that methamphetamine (METH) long-term abuse leads to chronic neurotoxicity, we put forward the hypothesis that persistent MAP and paranoid SCZ are different mental disorders. The hypothesis will be verified by transcriptomics RNA-sequencing, neuroimaging, event related potentials and mental symptom scales. Meanwhile, we collect the locus of differentially expressed genes among persistent MAP and paranoid SCZ, and establish scale-free networks of genes interrelationship and screen MAP-associated module enriched with characteristics genes closely related to symptom phenotype, neurotoxicity phenotype, cognitive impairment phenotype. This project is aimed to construct a biological marker system for the differential diagnosis of persistent MAP and paranoid SCZ, test the diagnostic value of the biological marker system in the practice, explore the genetic pathogenesis of persistent MAP and paranoid SCZ, and provide a scientific basis for the forensic practice.

本项目围绕在刑事责任能力司法鉴定中甲基苯丙胺所致精神病（MAP）与精神分裂症（SCZ）鉴别诊断的争议，根据甲基苯丙胺长期滥用导致慢性神经毒性损伤的证据，提出“持久型MAP与偏执型SCZ为不同的精神疾病”的假设，采用转录组学、神经影像学、事件相关电位及精神症状量表技术进行验证，获取持久型MAP、偏执型SCZ患者的差异表达基因位点，建立基因间相互关系的无尺度网络，筛选与精神症状特征表型、神经毒性损伤特征表型、认知功能缺陷特征表型密切相关的模块特征基因，构建一套用于持久型MAP与偏执型SCZ鉴别诊断的模块特征基因生物标记系统，并在实际鉴定案例中进行初步应用和验证，探索持久型MAP与偏执型SCZ不同的遗传发病机制，为法庭相关刑事责任能力的司法鉴定提供科学依据。

本项目聚焦以甲基苯丙胺为代表的毒性损伤所致精神损伤的鉴别诊断研究，建立一套有效和可靠的鉴别诊断技术，阐明甲基苯丙胺所致精神病与偏执型精神分裂症的发病机制，制定我国毒性损伤所致精神病的鉴定技术体系，为相关的司法鉴定提供科学依据，推动中国精神损伤理论的发展与转化运用。主要对甲基苯丙胺所致精神病与偏执型精神分裂症人口统计学与精神症状特征进行比较，分析偏执型精神分裂的易感基因。探索了两者的神经影像与事件相关电位表型特征，分析甲基苯丙胺所致精神病神经毒性损伤特点。检测患者对听觉刺激信息的门控感觉功能、认知加工处理能力，确定P300与P50可作为潜在疾病特征表型的价值。完成了甲基苯丙胺成瘾记忆机制研究，以及筛选肠道微生物组的数目、种群、动态分布及代谢变化等特征，探讨作为甲基苯丙胺滥用及中毒辅助诊断指标的可行性。