帕金森病抑郁症神经网络机制的多模态脑影像研究

Parkinson's disease (PD) is one of the most common neurodegenerative diseases in the elderly, and as high as 40% - 50% of PD patients are in depression, which was named depression in PD (dPD). Results of research suggest that both depressive symptoms and underlying neurobiological mechanisms of dPD might be different from those of the depressive disorder without PD. It could be assumed that dPD be a special "organic depression", however, the specific neural mechanism of dPD remains unclear. With magnetic resonance imaging (MRI) and drug intervention combined, PD patients without depression or patients with pure depression as control group, this project will follow up the brain structure and brain function imaging changes of dPD patients, who will accept different types of antidepressants, before and after the treatment. Based on multimodal and comprehensive brain imaging data analysis, neural network models would be constructed, and the neural pathological mechanism for dPD would be explored by: (1) whether the neural network model of dPD patients is different from those of patients with PD without depression and patients with pure depression; (2) what is the characteristic pathologic signs of neural network for dPD; (3) what are the different effects of antidepressants on the neural network in patients with dPD. This project will provide brain image index for early recognition and diagnosis of dPD, and offer new and scientific evidences for the diagnosis classification and individualized treatment of PD.

帕金森病（PD）为老年人最常见的神经退行性疾病之一，高达40%-50%的PD患者伴发抑郁，被称为帕金森病抑郁症（dPD），dPD的临床表现及神经机制不同于单纯的抑郁症，可能是一种特殊的"器质性抑郁"，但具体神经机制不明。本研究采用磁共振成像技术与药物干预相结合的方法，以药物作用机制作为切入点，以不伴抑郁的PD患者及单纯抑郁症作对照，追踪dPD患者在不同类型药物治疗前后的脑结构与脑功能影像变化，通过对多模态脑影像检测结果进行全面的比较分析，构建脑神经网络模型，从以下几方面探讨dPD的神经病理机制：（1）dPD患者是否存在不同于单纯PD及单纯抑郁的特征性神经网络模型；（2）dPD是否有特征性神经网络的病理性标志；（3）不同类型抗抑郁药对dPD患者神经网络的效应差异。该研究将为dPD的早期识别与诊断提供脑影像指标，为PD的分类诊断及个体化治疗提供新的思路和科学依据。

帕金森氏病（Parkinson’s disease, PD）是老年人中最为常见的一种复杂的、临床表现为一系列运动症状及非运动症状的中枢神经系统退行性疾病。其中，抑郁症状是 PD 最常见的非运动症状之一，PD患者抑郁症发生率明显高于普通人群，但其发生机制尚未明确，且PD患者的抑郁症状在临床上常被运动症状掩盖而未被及时诊断治疗。本课题采集多组被试的静息态、任务态、结构像磁共振（Magnetic resonance imaging, MRI）及扩散张量成像（Diffusion tensor imaging, DTI）等多模态脑影像数据，借助FSL、SPM等数据分析软件，对比了PD伴或不伴抑郁患者及健康对照之间脑结构和功能的改变，发现：(1)与PD不伴抑郁组比较，PD伴轻度抑郁组患者的双侧前额叶、部分双侧中央前回及部分左侧中央后回皮层厚度变薄，PD伴中重度抑郁组患者的右侧前额叶皮层厚度变薄；与健康对照组比较，PD伴轻度抑郁组脑皮层厚度无明显变化。(2)与PD不伴抑郁组相比，PD伴抑郁组右侧弓状束、下额枕束及扣带回白质部分各向异性（Fractional anisotropy, FA）值下降，且PD伴抑郁组弓状束FA值与抑郁程度呈负相关；(3)与PD不伴抑郁组比较，PD伴轻中度抑郁组左内侧和旁扣带回、左内侧额上回、左侧辅助运动区ReHo值减低，PD伴重度抑郁组双侧额中回、双侧扣带回、右侧运辅助动区ReHo值增⾼，右侧海马旁回、右侧⾆回ReHo值减低。这些研究结果提示PD伴抑郁的患者在特定的脑区及白质纤维束，尤其是前额叶-边缘系统，存在功能或结构的异常，这些研究结果为明确PD伴抑郁的神经病理学发生机制及早期临床诊断提供了新的依据。本课题按计划书严格实施，对所获数据进行深入分析，取得了系列研究成果，已发表了相关学术论文5篇和会议论文4篇，另有5篇论文已投稿。共有12名研究生直接参与到本课题实施中，其毕业论文将是本课题部分研究成果的体现。总的来讲，本课题已按计划基本完成，但本课题小组将继续深入挖掘数据，撰写与发表相关研究论文。