抑郁症是临床常见的严重精神疾病，病因和发病机制不详。5-羟色胺假说是目前被广泛接受的一种抑郁症的病因假说，5-羟色胺也是大多数抗抑郁剂的主要作用靶点，但该假说难以解释抗抑郁剂延迟起效的问题。近来影像学提示抑郁症特征性脑网络损害可能与抗抑郁剂疗效有关。本研究紧扣临床最关心的早期诊断、疗效预测等核心问题，立足于5-羟色胺假说，采用学科交叉方法，综合临床评估、药物治疗、分子遗传学、多模态影像学等研究方法，率先在中国汉族人群中选择高同质性抑郁症患者及相匹配的健康对照组，在基线（0周）和治疗8周末2个时点，动态观察患者临床表型（核心症状、疗效）、脑网络特征变化规律及相互关系，进一步分析5-羟色胺通路基因对二者进行的调控过程。应用多因素统计分析方法，多角度、多层面分析各项指标之间的内在关联，寻找抑郁症早期诊断、疗效预测的影像遗传学标记物，探讨抗抑郁剂延迟起效的脑网络基础，从而完善抑郁症5-羟色胺假说。

Major depressive disorder (MDD) is considered to be the most common psychotic disorder, but its etiology is still unclear. Serotonin hypothesis of depression is widely accepted and later marked as the target for antidepressant treatment, but it failed to explain the delay onset of antidepressants. Imaging studies imply the impairment of structral and functional brain networks has a close connection with the unsatisfactoriness of present drug treatment. This project focus on the early diagnosis and treatment outcome prediction. With the cross-field combination of clinical evalutaion, pharmaceutical treatment, molecular genetics and multi-modality functional magnetic resonance imaging, we recruited first-onset MDD patients of high homogeneity and matched controls in Chinese Han population. Based on the longitudinal follow-up at baseline (0 week) and 8 weeks after treatment carefully reviewed with the full evaluation of clinical data (core symptoms and treatment outcome) and altered patterns of brain networks, we will look into the serotonin pathway genes to assess their effect on the systems above. Multivariate statistic analysis will ensure the certain interactions among these different factors and help searching markers for diagnosis and treatment outcome prediction. This research will establish the brain network base for delay onset and add our present knowledge of serotonin hypothesis.