儿童期创伤与抑郁症发生的易感性和保护性神经网络机制研究

Major depressive disorder is one of the most common mental disorders with high rates of recurrence and disability. Despite the prevalence of depression and its considerable impact, knowledge about its pathophysiology is rudimentary. Moreover, the heterogeneous nature of depression lends substantially to the inconsistence of the published findings. Hence, it is imperative for researchers to explore the neurobiological bases for subtypes of depression. Childhood trauma is the strongest risk factors for developing major depression, and it is suggested that childhood trauma associated depression represents a clinically and biologically distinct subtype. Yet the neural underpinnings associated with childhood maltreatment in major depressive disorder remain poorly understood. Accordingly, we seek to investigate the characteristic structural and functional network changes that underlying the association between childhood trauma and major depressive disorder by using multi-model magnetic resonance imaging and a novel and solid imaging analysis technique-graph theory based approach. Importantly, we aim to study the modes of neural network that mediate the susceptibility and resiliency to major depressive disorder following childhood trauma. This would provide an understanding of how the brain mediates healthy recovery from childhood trauma, which would inform new insight to the diagnosis, prevention and therapy of childhood trauma-related depression and also provide viable neural processing targets for the individual treatment of depression.

抑郁症是最常见的精神障碍，其疾病负担在全世界致残疾病中位居第一。抑郁症的病因目前尚不清楚，其异质性是抑郁症病理机制研究中的瓶颈问题。而对具有特定表型特征和生物学特征的抑郁症亚型进行研究则能有效地减少其异质性，增加研究结果的稳定性和可靠性。儿童期创伤是抑郁症最主要的危险因素，儿童期创伤相关抑郁症具有独特的临床表型和神经生物学特征，是抑郁症的重要亚型，但儿童期创伤与抑郁症发生的病理机制尚不清楚。本研究在前期研究基础上，拟通过多模态磁共振成像技术从系统水平上来构建脑结构和功能网络，并采用基于图论的分析方法进行对脑网络定量分析，探讨儿童期创伤与抑郁症发生的脑网络机制，特别是个体对儿童期创伤差异性反应的神经网络机制，即经历儿童期创伤与抑郁症发生的易感性脑网络改变和保护性脑网络改变，并分析这些脑网络特征与儿童期创伤相关抑郁症临床特征的关系，从而探讨抑郁症的发生机制，寻找抑郁症的神经生物学标记。