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)：尽管有许多有效的干预措施可用于治疗严重抑郁障碍(MDD)，但治疗反应存在显著的异质性。提高治疗应答率的一个障碍是缺乏生物标记物来预测谁将对给定的治疗产生反应。此外，对抑郁症状和治疗反应的遗传中介缺乏了解。在试图从基因到抑郁表型之间形成联系的过程中，大脑活动是基因和行为之间的关键中介。在MDD中，多巴胺(DA)系统特别令人感兴趣，因为它们是奖赏反应(或其缺乏，快感缺失)的基础。这项建议将研究MDD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基因变异以及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已经是一个卓有成效的方法，但还没有被应用于理解MDD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)期间接受功能神经成像，并将在开始简短的抑郁症行为激活治疗(BATD)心理治疗之前接受候选多巴胺基因(COMT、DAT1和其他)的基因分型。候选DA基因的多态将被检测为额纹状体奖赏网络激活和心理治疗反应的预测因子。额纹状体奖赏网络的激活将作为DA多态对治疗反应影响的中介进行进一步研究。这种方法是一项研究计划中的重要一步，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MDD对药物和心理治疗抗抑郁药物的反应。