Neuroimaging Major Depression and Nicotine Dependence on Axes of Valuation

说明(申请人提供)：严重抑郁障碍和物质依赖分别是导致美国和世界人口死亡和残疾的最重要原因之一(世卫组织，2008年；疾控中心，2005年)。虽然严重的抑郁和成瘾传统上被作为不同的现象进行研究，但有趣的证据表明，常见神经行为情感和动机系统中的截然不同的损害可能是这些障碍的病因，并导致抑郁症中物质依赖的高发。功能神经成像的最新进展，加上新的分析方法，以及新出现的数据表明，可能需要重新概念化这些条件。具体地说，物质依赖(包括尼古丁依赖)和严重抑郁的关键方面可能会在通常用于量化“动机行为”或“估值”的轴线的两端进行量化。在这样做的过程中，可能会阐明重度抑郁症与物质依赖高并存的病理生理学基础，并导致改善对这些疾病的诊断和治疗，因为它们是单独和共同发生的。因此，这个项目的广泛目标是识别和提炼一个共同的神经行为空间，在这个空间内，抑郁症和尼古丁依赖的估值异常可能被理解。我们认为，最近在动机行为的四个领域的功能神经成像数据为这项工作提供了初步的方向；这些领域是：(I)影响/线索反应；(Ii)奖赏/损失引导的概率学习；以及(Iii)对反事实信号的反应。我们相信，这些数据将促进以下领域的进展：a)澄清尼古丁依赖和抑郁的动机行为的共同和独特的神经病理学，以及b)提供导致尼古丁依赖和抑郁共存的高患病率的神经行为异常的初步数据。 公共卫生相关性：吸烟和严重抑郁障碍分别是导致美国和全世界人口死亡和残疾的最重要原因(世卫组织，2008年；疾控中心，2005年)。我们相信，这些数据将有助于在以下领域取得进展：a)澄清尼古丁依赖和抑郁的共同和独特的动机行为的神经病理，以及b)提供导致尼古丁依赖和抑郁共存的高患病率和特别是衰弱效应的神经行为异常的初步数据。尼古丁依赖和严重抑郁症造成的人力和财政成本促使人们试图确定可用于理解这些疾病的病理生理学的量化神经行为指标。

DESCRIPTION (provided by applicant): Major depressive disorder and substance dependence, respectively, rank among the most significant causes of mortality and disability in the American and worldwide populations (WHO, 2008; CDC, 2005). While major depression and addiction have traditionally been studied as distinct phenomena, intriguing evidence suggests that diametrical impairments in common neurobehavioral affect and motivation systems may underlie the disorders' etiologies and contribute to the high prevalence of substance dependence in depression. Recent advances in functional neuroimaging, coupled with novel analytic methods, and emerging data suggest that a re-conceptualization of the conditions may be warranted. Specifically, key aspects of substance dependence (including nicotine dependence) and major depression may be quantified on extreme ends of axes commonly used to quantify "motivated behavior" or "valuation". In doing so, the pathophysiology underlying the high co- morbidity of major depression with substance dependence may be elucidated and lead to improved diagnostics and therapies for the conditions as they occur separately and together. Thus, the broad goal of this project is to identify and refine a common neurobehavioral space within which anomalies of valuation in depression and nicotine dependence may be understood. We suggest that recent functional neuroimaging data in four domains of motivated behavior provide an initial direction for this work; these areas are: (i) affect/cue reactivity; (ii) reward/loss-guided probabilistic learning; and (iii) responses to counterfactual signals. We believe that these data will facilitate advances in the following areas: a) clarifying the common and distinct neuropathology of motivated behavior in nicotine dependence and depression, and b) providing initial data on neurobehavioral anomalies that contribute to the high prevalence of co-occurring nicotine dependence and depression. PUBLIC HEALTH RELEVANCE: Cigarette smoking and major depressive disorder, respectively, rank among the most significant causes of mortality and disability in the American and worldwide populations (WHO, 2008; CDC, 2005). We believe that these data will facilitate advances in the following areas: a) clarifying the common and distinct neuropathology of motivated behavior in nicotine dependence and depression, and b) providing initial data on neurobehavioral anomalies that contribute to the high prevalence and particularly debilitating effects of co-occurring nicotine dependence and depression. The human and fiscal cost of nicotine dependence and major depression motivates the attempt to identify quantitative neurobehavioral measures that may be used to understand the pathophysiology of the conditions.