Neural Correlates of Loss Aversion in Major Depression

描述(申请人提供)：这项资助申请的目的是使我能够成为一名独立的临床研究人员，拥有将功能磁共振成像(FMRI)和神经经济学技术应用于情绪和焦虑症患者的专业知识。这项为期三年的拨款申请建立在2007年年中我从埃默里获得的为期两年(K12/KL2)的内部奖励之上。积极的指导、授课和拟议项目的完成构成了培训的组成部分。这项拟议的研究的目标是确定严重抑郁障碍(MDD)患者对丧失敏感性的神经学相关性。这一目标将通过将神经经济学框架应用于MDD的研究来实现。特别是，“损失厌恶”这一神经经济学概念将在抑郁症患者和对照组受试者之间进行比较。这项研究有两个具体目的：(1)测量和比较抑郁症患者和健康对照组的损失厌恶；(2)探索损失厌恶与大脑奖励系统结构内神经活动模式之间的关联。这项横断面研究将采用一项赌博任务，证明在健康对照组做出关于潜在收益或损失的决定时，他们的大脑区域会被不同地激活。30对匹配的中度到重度抑郁症患者和健康对照组将被纳入，在年龄、性别和年收入方面进行匹配。用他们通过完成测试程序赚到的钱，参与者将选择是否接受一系列可能会带来收益或损失的赌博。这些决定将在3Tesla功能磁共振扫描仪中进行的与事件相关的试验设计中做出。这项研究的假设是，与对照组相比，抑郁症患者对损失的敏感度较低，即损失厌恶程度降低，这些选择将与奖励系统回路(如腹侧纹状体和眼眶额叶皮质)内神经活动从静止状态的较小变化相关联。如果得到证实，这些假设可能会让我们了解抑郁症患者如何做出违背他们最大利益的选择，并将他们置于进一步的经济或人际损失的风险中，甚至可能是自我导向的伤害。与公共健康相关：患有严重抑郁症的人经常对自己的生活做出有害的选择。了解抑郁症患者如何做出这样的选择的生物学基础可能有助于临床医生预防这种有害决定可能造成的伤害，例如失去工作、失去关系，甚至失去对自己生活的关注。

DESCRIPTION (provided by applicant): The purpose of this grant application is to enable me to become an independent clinical researcher, with expertise in applying the techniques of functional magnetic resonance imaging (fMRI) and neuroeconomics to patients with mood and anxiety disorders. This three year grant request builds on a 2-year (K12/KL2) internal award I received from Emory in mid-2007. Active mentoring, didactic coursework, and the completion of the proposed project constitute the training components. The goal of the proposed study is to identify the neurological correlates of sensitivity to loss in major depressive disorder (MDD). This goal will be achieved by applying a neuroeconomics framework to the study of MDD. In particular, the neuroeconomics concept of "loss aversion" will be compared between depressed and control subjects. The study has two specific aims: (1) to measure and compare loss aversion among depressed patients and healthy controls; (2) to explore the association between loss aversion and patterns of neural activity within the structures of the reward system of the brain. This cross-sectional study will employ a gambling task demonstrated to differentially activate brain regions in healthy controls as they make decisions about potential gains or losses. Thirty matched pairs of moderate to severely depressed patients and healthy control subjects will be enrolled, matched on age, gender and annual income. Using money they have earned through completing testing procedures, participants will choose whether or not to accept a series of gambles that offer a potential gain or loss. These decisions will be made within an event-related trial design administered in a 3 Tesla fMRI scanner. Hypotheses for the study are that, compared with controls, depressed patients will demonstrate lower sensitivity to losses, i.e. reduced levels of loss aversion, and that these choices will correlate with smaller changes from resting state in neural activity within reward system circuitry, such as the ventral striatum and orbital frontal cortex. If proven, these hypotheses may inform our understanding of how depressed patients make choices against their best interests, and put themeselves at risk for further financial or interpersonal losses, and possibly self-directed harm. PUBLIC HEALTH RELEVANCE: People suffering from major depression often make choices about their lives that are detrimental to themselves. Understanding the biological basis of how depressed people make such choices may help clinicians prevent the harm that can arise from such detrimental decisions, such as loss of jobs, relationships, or even loss of concern for one's own life.