Neuroanatomy of Anticipation in Anxiety Disorders

焦虑症预期的神经解剖学

• 批准号: 7097385
• 负责人: Jack B Nitschke
• 金额: $ 30.02万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-20 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7097385
• 关键词: anxiety disorders; behavioral /social science research tag; bioimaging /biomedical imaging; clinical research; functional magnetic resonance imaging; human subject; major depression; mental process; neural information processing; neurophysiology; patient oriented research; psychobiology

DESCRIPTION (provided by applicant): Anxiety and mood disorders are debilitating conditions that cause tremendous personal suffering and engender a high societal and economic burden. A central feature of these disorders is excessive anticipation of potentially aversive outcomes. While anticipation is critical for successful preparation and adaptation to aversive events, dysfunction in this system can interfere markedly with social and occupational functioning. By investigating the neurobiology of this anticipatory system, neural areas associated with specific functions of anticipation, such as autonomic processing, negative affect, and behavioral withdrawal, can be identified and targeted by psychological or biological treatments. In addition, the proposed event-related functional magnetic resonance imaging (fMRI) studies capitalize on 2 key characteristics of anticipation: uncertainty about the future and an inability to control it. Building on prior research using an anticipation paradigm with 1 warning symbol that predicts aversive pictures and another predicting neutral, the first study will manipulate uncertainty (i.e., predictability of picture content) by including an ambiguous warning symbol that is followed by either aversive or neutral pictures. The second study will manipulate uncontrollability by including a condition in which a behavioral response can shorten picture duration. The influence of uncertainty and uncontrollability on key neural areas in the proposed model for aversive anticipation will be tested with healthy volunteers in the first 2 studies. For the final study, both paradigms will be used with relevant clinical populations-generalized anxiety disorder, social anxiety disorder (social phobia), and major depressive disorder-to determine how the normative circuitry identified in the first 2 studies is aberrant in anxiety and mood disorders. The primary prediction is that there is a neural signature for anxiety disorders that corresponds to a general dysfunction in anticipatory processes engaged by potential aversive outcomes, especially in situations of uncertainty and uncontrollability. In sum, the emphasis of this application on the capacity to anticipate impending danger is a novel approach to the study of affective disorders that is geared toward basic knowledge about the neurobiology of healthy defense mechanisms (e.g., anticipation that results in adaptive response) as well as understanding how dysfunction in this system occurs.

描述(由申请人提供)：焦虑和情绪障碍是导致巨大个人痛苦和产生高社会和经济负担的衰弱状况。这些障碍的一个核心特征是过度预期可能令人厌恶的结果。虽然预期是成功准备和适应厌恶事件的关键，但这一系统的功能障碍会显著干扰社会和职业功能。通过研究这种预期系统的神经生物学，与预期的特定功能相关的神经区域，如自主神经处理、负面情绪和行为撤退，可以通过心理或生物治疗来识别和靶向。此外，拟议的事件相关功能磁共振成像(FMRI)研究利用了预期的两个关键特征：对未来的不确定性和无法控制未来。在先前研究的基础上，使用预期范式，其中一个警告符号预测厌恶图片，另一个预测中性图片，第一个研究将操纵不确定性(即，图片内容的可预测性)，方法是包括一个模糊警告符号，然后是厌恶图片或中性图片。第二项研究将通过包括行为反应可以缩短画面持续时间的条件来操纵不可控性。在前两项研究中，我们将在健康志愿者身上测试厌恶预期模型中不确定性和不可控性对关键神经区域的影响。在最后一项研究中，这两种范式都将用于相关临床人群--广泛性焦虑症、社交焦虑症(社交恐惧症)和严重抑郁障碍--以确定前两项研究中确定的标准回路在焦虑和情绪障碍中是如何异常的。初步的预测是，焦虑症有一个神经标志，对应于潜在厌恶结果参与的预期过程中的一般功能障碍，特别是在不确定和不可控的情况下。总之，这一应用的重点是预测即将到来的危险的能力，这是一种研究情感障碍的新方法，旨在了解健康防御机制的神经生物学基础知识(例如，导致适应性反应的预期)以及了解这个系统中的功能障碍是如何发生的。