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成为一名独立的临床研究人员，具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障碍患者的专业知识。这项为期三年的资助申请建立在2007年中期我从埃默里大学获得的为期2年（K12/KL2）的内部奖励的基础上。积极的指导、说教式的课程作业和完成拟议的项目构成了培训的组成部分。本研究的目的是确定重性抑郁障碍（MDD）患者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“损失厌恶”概念将在抑郁症和对照组受试者之间进行比较。本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情绪；(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系。这项横断面研究将采用一项赌博任务，在健康对照组做出关于潜在收益或损失的决定时，被证明能不同地激活大脑区域。在年龄、性别和年收入上匹配的30对中重度抑郁症患者和健康对照者将被纳入研究。参与者将使用他们通过完成测试程序赚到的钱，选择是否接受一系列可能有收益或损失的赌博。这些决定将在一个与事件相关的试验设计中做出，该试验设计在一个3特斯拉的功能磁共振成像扫描仪中进行。该研究的假设是，与对照组相比，抑郁症患者对损失的敏感度较低，即对损失的厌恶程度较低，而且这些选择与奖赏系统回路（如腹侧纹状体和眶额皮质）内神经活动的静息状态变化较小有关。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损失风险中，甚至可能是自我伤害。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些选择的生物学基础，可能有助于临床医生预防这些有害决定所带来的伤害，比如失去工作、失去人际关系，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.