Neuroimaging Major Depression and Nicotine Dependence on Axes of Valuation

描述（由申请人提供）：在美国和世界范围内，重度抑郁症和物质依赖分别是导致死亡和残疾的最重要原因（WHO, 2008； CDC, 2005）。虽然重度抑郁症和成瘾一直被视为不同的现象，但有趣的证据表明，常见神经行为影响和动机系统的明显损伤可能是疾病病因的基础，并有助于抑郁症中物质依赖的高患病率。功能神经影像学的最新进展，加上新的分析方法和新出现的数据表明，可能需要对这些条件进行重新概念化。具体而言，物质依赖（包括尼古丁依赖）和重度抑郁症的关键方面可以在通常用于量化“动机行为”或“评估”的坐标轴的极端末端进行量化。这样，重性抑郁症与物质依赖的高发病率的病理生理学可能会被阐明，并导致改善诊断和治疗条件，因为它们分别发生和一起发生。因此，这个项目的广泛目标是确定和完善一个共同的神经行为空间，在这个空间中，抑郁和尼古丁依赖的估值异常可能被理解。我们认为，最近在四个动机行为领域的功能神经影像学数据为这项工作提供了一个初步的方向；这些领域是：(i)影响/提示反应性；（ii）奖励/损失导向概率学习；（三）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)阐明尼古丁依赖和抑郁中动机行为的共同和独特的神经病理学；b)提供导致尼古丁依赖和抑郁同时发生的高患病率的神经行为异常的初步数据。

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.