Imaging Genetic Predictors of Psychotherapy Outcomes in Unipolar Depression

单相抑郁症心理治疗结果的影像遗传预测因子

• 批准号: 8456070
• 负责人: GABRIEL S DICHTER
• 金额: $ 21.96万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-06 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8456070
• 关键词: Adult; Alleles; Anhedonia; Animals; Antidepressive Agents; Area; Behavior; Behavioral; Biological; Biological Markers; Brain; Candidate Disease Gene; Catabolism; Catechol O-Methyltransferase; Characteristics; Clinical; Corpus striatum structure; Depressed mood; Disease; Dopamine; Feedback; Functional disorder; Genes; Genetic; Genetic Models; Genetic Polymorphism; Genotype; Goals; Heterogeneity; Heterozygote; Homozygote; Human; Image; Incentives; Individual; Intervention; Link; Longevity; Major Depressive Disorder; Mediator of activation protein; Mental Depression; Mental disorders; Methyltransferase Gene; Modeling; National Institute of Mental Health; Outcome; Output; Participant; Patients; Phase; Phenotype; Prefrontal Cortex; Psychotherapy; Public Health; Recovery; Relative (related person); Research; Rewards; Risk; Risk Factors; Role; Strategic Planning; System; Unipolar Depression; Variant; burden of illness; cognitive neuroscience; depressive symptoms; disability; dopamine system; effective intervention; improved; improved functioning; interest; meetings; methionylmethionine; mortality; neuroimaging; programs; relating to nervous system; response; reward processing; treatment response; valylvaline

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.

描述（由申请人提供）：尽管可用的主要抑郁症（MDD）有许多有效的干预措施，但治疗反应有明显的异质性。改善治疗反应率的一个障碍是缺乏生物标志物来预测谁将对特定的治疗做出反应。此外，缺乏对抑郁症状和治疗反应的遗传介体的了解。在尝试形成从基因到抑郁表型的链接的尝试，大脑活动是基因和行为之间的关键中间。在MDD中，多巴胺（DA）系统特别令人感兴趣，因为它们是奖励反应性的基础（或缺乏奖励，Anhedonia）。该提案将研究MDD中神经对奖励的反应，这是调节DA系统功能输出的候选基因的等位基因变化，以及对心理治疗的反应。成像基因学一直是基本和临床认知神经科学的富有成果的方法，但尚未应用于MDD中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）期间进行功能性神经影像学，并在启动短暂行为激活治疗抑郁症（BATD）心理治疗的过程之前，将对候选多巴胺基因（COMT，DAT1等）进行基因分型。候选DA多态性将被检查为额 - 纹状体奖励网络激活以及心理治疗治疗反应的预测指标。额叶奖励网络激活将进一步研究，作为对治疗反应的DA多态性影响的介体。这种方法是研究计划中的重要一步，其最终目的是生成和验证成像遗传模型，这些遗传模型可能最终可以预测MDD中对药理和心理治疗抗抑郁治疗的反应。