抑郁障碍早期治疗反应的神经标记及其性别效应

Depression is one of the most prevalent mental disorders, with higher rates in women. Also, the current pharmacological treatments are limited by low response rates during the first treatment attempt. Therefore there is an urgent need to determine early markers for treatment response and gender effects. Based on the marked affective-cognitive dysfunctions in depression, the current project therefore aims to determine early neural markers for subsequent treatment response and potential gender differences using a prospective randomized-controlled treatment response fMRI design in patients with major depression. 80 first-episode major depressive disorder (MDD) patients (40 males) will undergo psychopathological characterization, emotional prosody and fMRI tasks assessing face recognition before (baseline), after 2-weeks (early treatment markers) and 12-weeks (treatment response evaluation) of treatment with Escitalopram. Another 80 healthy controls (40 males) will complete the baseline assessment to determine neural markers associated with symptom and behavioral markers for the disorder. To determine early treatment markers, data from 2 weeks following treatment will be examined by comparing responders and non-responders determined by the follow up at 12-weeks of treatment. To determine steady predictors, neural changes at 2-weeks will be correlated with behavioral improvement at 2-weeks as well as 12-weeks. Both analyses will additionally explore gender differences in the disorder as well as treatment response markers. Determining prospective treatment success markers and gender differences following two weeks will promote determining early treatment response and may considerably reduce the time for successful treatment. Moreover, within a personalized medicine approach, the gender differences may promote selection of the most promising treatment strategies for men and women. The findings thus may have a profound influence on behavioral science, neuroscience, psychopathology, as well as the clinical application research.

抑郁障碍是最普遍的精神疾病之一。由于女性患病率显著高于男性，且首次药物治疗尝试响应率低，因此确定早期治疗反应的相关标记及其性别效应尤为迫切。本项目根据其情绪认知功能失调的特点，通过心理实验法和fMRI脑成像技术，招募80名首发抑郁障碍患者（40男），分别在未治疗时（基线）和使用抗抑郁药物艾司西酞普兰治疗2周（确定早期反应）及12周时（评估后期反应），完成问卷填写和情绪面孔识别与评定任务。同时，80名匹配的健康被试将完成基线测试，来确定患者与症状和行为显著相关的异常的神经标记及其性别效应。再基于此结果比较治疗2周前后的神经改变，及其与治疗12周后行为改善的相关性，确定可以识别和预测治疗效果的神经标记及其性别效应。本项目的研究结果，有望为缩短治疗时长，以及针对性地诊断和治疗男性和女性患者提供帮助，具有丰富行为科学、神经科学、精神病理学等理论研究，以及临床应用研究的双重意义。

抑郁障碍是最普遍的精神疾病之一，女性患病率显著高于男性，且首次药物治疗尝试响应率低。本项目根据抑郁障碍患者情绪认知功能失调的显著特点，采用心理学实验法和功能磁共振成像技术，考察抑郁障碍早期治疗反应的神经标记及其性别效应。首先，本项目修改完善后的融合情绪面孔加工范式能有效观察到神经行为变化，为后续系列研究的开展做好了铺垫。基于此研究范式，项目考察了首发抑郁障碍患者SSRI药物治疗前后的变化，并得到了初步结果：在症状上，患者的抑郁自评量表等得分在治疗后有明显下降；在行为上，患者的融合情绪面孔识别，尤其是在将面孔识别为中性和悲伤情绪的比例上，与未治疗时相比，治疗后有显著改变；在神经上，抑郁障碍患者未治疗时对融合情绪面孔的神经反应更强，治疗后对未融合情绪面孔的神经反应更强，其中额下回的神经反应降低或许可以作为反映治疗效果的神经标记。同时，项目考察了融合情绪面孔加工时的性别差异，结果显示，女性将面孔识别为悲伤的比例显著高于男性，而边缘系统和默认网络相关脑区对情绪面孔的神经反应也存在显著的性别差异。此外，项目研究结果还发现，与健康对照组相比，抑郁障碍患者在情绪认知加工时表现为负性情绪加工偏向和正性情绪缺失；患者脑干的功能连接和前额叶的内在连通性也存在显著异常；大脑边缘系统的神经反应及其功能连接与抑郁水平显著相关。因此，从理论上，该项目对已有的抑郁障碍研究进行了实证补充，丰富了行为科学、神经科学、精神病理学等理论体系；从应用上，为抑郁障碍的诊断与治疗提供了一定的理论依据。