Imaging Genetic Predictors of Psychotherapy Outcomes in Unipolar Depression

描述（由申请人提供）：虽然有许多有效的干预措施可用于重度抑郁症（MDD），但治疗反应存在显著的异质性。提高治疗反应率的一个障碍是缺乏生物标志物来预测谁将对给定的治疗有反应。此外，缺乏对抑郁症状和治疗反应的遗传介质的了解。在试图形成基因与抑郁表型之间的联系时，大脑活动是基因与行为之间的关键中介。在重度抑郁症中，多巴胺（DA）系统特别有趣，因为它们是奖励反应（或其缺乏，快感缺乏）的基础。本研究将研究重度抑郁症患者对奖励的神经反应、调节DA系统功能输出的候选基因的等位变异以及对心理治疗的反应之间的关系。成像遗传学在基础和临床认知神经科学中是一种卓有成效的方法，但尚未应用于理解重度抑郁症心理治疗反应的异质性。参与者将在奖励预期和反馈任务（货币激励延迟）中进行功能神经成像，并在开始短暂行为激活治疗抑郁症（BATD）心理治疗之前对候选多巴胺基因（COMT， DAT1等）进行基因分型。候选DA多态性将作为额纹状体奖励网络激活和心理治疗反应的预测因子进行研究。额纹状体奖赏网络激活将进一步作为DA多态性对治疗反应影响的中介。该方法是研究项目的重要一步，其最终目标是生成和验证成像遗传模型，该模型可能最终预测对重度抑郁症药物和心理治疗抗抑郁药物治疗的反应。

DESCRIPTION (provided by applicant): Though there are many effective interventions for Major Depressive Disorder (MDD) available, there is significant heterogeneity in treatment response. One obstacle to improved treatment response rates is the lack of biomarkers to predict who will respond to a given treatment. Further, there is a lack of understanding of genetic mediators of both depressive symptoms and treatment response. In the attempt to form links from genes to depressive phenotype, brain activity is a key intermediate between genes and behavior. In MDD, dopamine (DA) systems are of particular interest, as they underlie reward responsivity (or its lack, anhedonia). This proposal will examine relations between neural response to rewards in MDD, allelic variations of candidate genes regulating functional output of DA systems, and response to psychotherapy. Imaging-genetics has been a fruitful approach in basic and clinical cognitive neuroscience but has not yet been applied to understand heterogeneity of psychotherapy response in MDD. Participants will undergo functional neuroimaging during a reward anticipation and feedback task (Monetary Incentive Delay) and will be genotyped for candidate dopamine genes (COMT, DAT1, and others) before initiating a course of Brief Behavioral Activation Treatment for Depression (BATD) psychotherapy. Candidate DA polymorphisms will be examined as predictors of both fronto-striatal reward network activation as well as psychotherapy treatment response. Fronto-striatal reward network activation will be examined further as a mediator of DA polymorphism effects on treatment response. This approach is an important step in a program of research with the ultimate goal of generating and validating imaging genetic models that may ultimately predict response to both pharmacological and psychotherapeutic antidepressant treatments in MDD.