双相情感障碍和精神分裂症脑复杂网络异常与肠道菌群失调相关性初探

Both bipolar disorder (BD) and schizophrenia (SZ) are common, harmful mental diseases. Two diseases have many similarities, such as susceptibility genes, prodromal symptoms, abnormalities of brain structure and function, and cognitive impairments. Thus, the rate of misdiagnosis between BD and SZ is relatively high. Although the pathogenesis of two diseases remains largely unknown, recent studies have shown that the disruption of “Brain-Gut-Microbiota axis” is highly related with mental diseases. Our preliminary studies found that: 1) first-episode, drug-naïve SZ (feSZ) patients show abnormalities of functional brain connectivity; 2) chronic SZ patients show severe abnormalities of structural brain connectivity compared with feSZ patients; 3) chronic patients show alterations in the composition of fecal microbiota. In this study, we plan to recruit first-diagnosis, drug-naïve BD (fdBD) and feSZ patients and collect their multi-modal MRI (including T1, DTI, rs-fMRI) data and samples of feces. Human connectome analysis will be applied to analyze topological properties of structural and functional brain networks constructed from multi-modal MRI data. Methods of metagenomics will be used to analyze the species and gene in get microbiota. This study will try to investigate: 1) the convergence and divergence of brain network dysfunction in patients with fdBD and feSZ; 2) the alterations of gut microbiota in patients with fdBD and feSZ; and 3) the correlations between neural circuits and gut microbiota. The results of this study have potential of identifying biological markers for the early warning, diagnosis, prevention, and treatment of fdBD and feSZ patients.

双相情感障碍(BD)和精神分裂症(SZ)都是常见、危害极大的重性精神疾病，两者在易感基因、前驱核心症状、脑结构和功能异常、认知功能损伤等方面有很多相似性，临床上容易造成误诊。虽然BD和SZ的发病机制还不明确，最近许多研究表明“脑-肠-微生物轴”功能的紊乱与精神疾病之间的关系密切。我们前期研究了SZ患者的神经影像和肠道菌群，发现首发未用药SZ患者已经显现出脑功能改变，而慢性SZ患者的脑结构损伤较为严重，慢性SZ患者还存在肠道菌群的紊乱。本研究以首次诊断未用药BD和首发未用药SZ患者为研究对象，基于多模态MRI图像构建脑结构及功能网络，采用人脑连接组学技术分析脑网络拓扑结构及属性，采用宏基因组学分析肠道菌群物种及基因。本项目将从系统水平上揭示BD与SZ神经环路异常的相似性及特异性，揭示两种疾病患者肠道菌群失调的特征，初步探讨脑复杂网络异常与肠道菌群失调的相关性，具有重要的临床价值和市场前景。

双相情感障碍(BD)和精神分裂症(SZ)都是常见、危害极大的重性精神疾病，基于人脑连接组学、微生物组学、机器学习等技术，研究BD和SZ神经环路异常与肠道菌群失调之间的相关性，有助于理解二种精神疾病的神经病理机制。本项目系统研究了二种精神疾病脑影像特征、脑复杂网络属性、电生理特征、肠道菌群特征、血液生化指标、神经心理测评等多生物学特征的特异性，开发了基于多生物学表征的AI辅助诊断算法，研制了神经影像大数据分析平台、心理健康多维度信息人工智能分析系统等软件。重要结果包括：①采用结构磁共振图像和静息态磁共振图像分别构建脑结构和功能网络，分析发现SZ患者在不同的病程阶段，其结构-功能连接性耦合强度存在显著差异；②SZ患者肠道菌群的Alpha多样性与顶叶、颞叶和岛叶等脑区的灰质体积、局部一致性（ReHo）呈显著线性相关；此外，Roseburia菌属在SZ患者肠道中相对丰度降低，且其相对丰度值与左侧楔叶、右侧颞叶上回和右侧颞叶中回等大脑皮层的ReHo值呈显著负相关；③基于肠道菌群、血液指标及脑电特征等多生物学表征，采用五种机器学习分类器、三种特征选择算法和四种交叉验证方法组成的集成学习框架，构建的SZ自动分类模型最优性能指标分别为准确率91.7%。本项目成果在国际上首次报道了精神分裂症脑结构及功能异常与肠道菌群紊乱之间的相关性，将有助于阐明精神分裂症的神经病理机制；基于多生物学表征构建的AI辅助诊断模型，为精神疾病诊断的生物学标记物研究提供了新思路。