Neural Correlates of Loss Aversion in Major Depression

描述（由申请人提供）：本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，具有将功能性磁共振成像（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。这三年的赠款申请建立在我在2007年年中从埃默里大学获得的2年（K12/KL 2）内部奖励的基础上。积极的辅导、教学课程和完成拟议项目构成培训的组成部分。这项研究的目的是确定重性抑郁症（MDD）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，神经经济学的概念“损失厌恶”将在抑郁症和控制受试者之间进行比较。该研究有两个具体目标：（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，证明在健康对照组中，当他们对潜在的收益或损失做出决定时，会有差异地激活大脑区域。将入组30对匹配的中度至重度抑郁患者和健康对照受试者，年龄、性别和年收入匹配。使用他们通过完成测试程序赚来的钱，参与者将选择是否接受一系列提供潜在收益或损失的赌博。这些决定将在3特斯拉fMRI扫描仪中进行的事件相关试验设计中做出。该研究的假设是，与对照组相比，抑郁症患者对损失的敏感性较低，即损失厌恶水平降低，并且这些选择将与奖励系统回路（如腹侧纹状体和眶额叶皮层）内神经活动的静息状态变化较小相关。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自己最大利益的选择，并将自己置于进一步的经济或人际关系损失的风险中，甚至可能是自我导向的伤害。公共卫生相关性：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种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引起的伤害，例如失去工作，关系，甚至失去对自己生命的关注。

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.