Neuroimaging Major Depression and Nicotine Dependence on Axes of Valuation

描述（由申请人提供）：重度抑郁症和物质依赖分别是美国和全球人群死亡和残疾的最重要原因（WHO，2008; CDC，2005）。虽然重性抑郁症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，常见的神经行为影响和动机系统的直接损伤可能是这些疾病的病因学基础，并导致抑郁症中物质依赖的高患病率。功能性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，重新概念化的条件可能是必要的。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“评价”的轴的极端上进行量化。在这样做时，可以阐明重性抑郁症与物质依赖的高共发病率的病理生理学，并导致对单独和一起发生的病症的改进的诊断和治疗。因此，该项目的广泛目标是确定和完善一个共同的神经行为空间，在这个空间内，可以理解抑郁症和尼古丁依赖的异常估值。我们认为，最近在动机行为的四个领域的功能神经影像学数据提供了一个初步的方向，这些领域是：（i）影响/线索反应;（ii）奖励/损失引导的概率学习;（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）阐明尼古丁依赖和抑郁症中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症并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：吸烟和重度抑郁症分别是美国和全球人群死亡和残疾的最重要原因（WHO，2008; CDC，2005）。我们认为，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症中动机行为的共同和独特的神经病理学，以及B）提供有关神经行为异常的初始数据，这些异常导致尼古丁依赖和抑郁症的高患病率，特别是使人衰弱的影响。尼古丁依赖和重度抑郁症的人力和财政成本促使人们尝试确定可用于了解这些疾病的病理生理学的定量神经行为指标。

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.