Cognitive Phenotype Neural Circuitry in vivo in Mood Disorders and Suicidal Beha

在过去的十年中，描述和治疗精神疾病的一个重要方法是应用认知神经科学技术来理解临床功能障碍背后的神经机制。例如，相对于健康志愿者，重度抑郁症（MDD）患者 可能显示与认知控制有关的脑系统的低激活（例如，背侧和腹外侧 前额叶皮层，dIPFC和vIPFC）和涉及触发情绪的系统的过度激活 反应（例如杏仁核）。特别令人感兴趣的是，这种模式在多大程度上可能与非 但与抑郁发作相关的自杀风险。虽然迄今为止几乎没有功能 成像数据已经解决了这个问题，来自康特中心实验室的PET和尸检工作表明， 腹外侧PFC和前扣带回功能减退，以及血清素转运体结合降低， 杏仁核和腹侧/眶PFC可能会导致自杀或非致命性自杀企图的风险。这 一项提案试图澄清这些联系，建立在一个新兴的情绪认知控制模型的基础上， 健康的成年人来检查情绪调节的特定认知策略的神经基础-被称为 重新评估-在有自杀企图的重度抑郁症患者（MDD-Atts）中， 从未尝试过自杀（MDD-非Atts）、健康志愿者（HV）和目前无抑郁症的成年人 MDD-Att的后代可能有更高的自杀风险（HR）。在目标1 - 3中，我们将比较神经 MDD-Atts、MDD-NonAtts和HV的重新评估表现的相关性，以确定抑郁 一般来说，个体，特别是那些企图自杀的人（目标1）产生更强烈的负面影响。 （目标2）产生较弱的积极情绪，或者 更大的麻烦，或显示出目标1和2下的调节相关活动模式， （探索性目的3）与5-HT功能异常（见P3）、童年逆境、压力有关 反应性和/或侵略性（参见CEC）。在探索性目标4中，我们询问HR是否表现出反应 目标1 - 3下的模式类似于Atts，从而表明倾向于自杀的素质。

Over the past decade an important approach to describing and treating psychiatric disorders has been the application of cognitive neuroscience techniques to understanding the neural mechanisms underlying clinical dysfunction. For example, relative to healthy volunteers, individuals with major depressive disorder (MDD) may show hypoactivation of brain systems implicated in cognitive control (e.g. dorsal and ventrolateral prefrontal cortex, dIPFC and vIPFC) and hyperactivation of systems implicated in triggering emotional responses (e.g. the amygdala). Of particular interest is the extent to which such patterns may be related not just to MDD, but to suicide risk associated with depressive episodes. Although to date little functional imaging data have addressed this question, PET and postmortem work from Conte Center labs has shown that ventrolateral PFC and anterior cingulate hypofunction, as well as lower serotonin transporter binding in the amygdala and ventral/orbital PFC, may contribute to the risk of suicide or nonfatal suicide attempts. This proposal seeks to clarify these links, building on an emerging model of the cognitive control of emotion in healthy adults to examine the neural bases of a specific cognitive strategy for emotion regulation - known as reappraisal - in individuals with major depressive disorder who have attempted suicide (MDD-Atts), who have never attempted suicide (MDD-Non-Atts), healthy volunteers (HVs) and currently non-depressed adult offspring of MDD-Atts who may be at higher risk for suicide (HRs). In Aims 1-3, we will compare the neural correlates of reappraisal performance of MDD-Atts, MDD-NonAtts, and HVs to determine whether depressed individuals in general, and those who attempt suicide in particular (Aim 1) generate stronger negative emotions or have greater trouble down-regulating them, (Aim 2) generate weaker positive emotions or have greater trouble up-regulating them, or show patterns of regulation-related activity under Aims 1 and 2 that (Exploratory Aim 3) are related to abnormalities in 5-HT function (see P3), childhood adversity, stress responsiveness and/or aggression (see CEC). In Exploratory Aim 4 we ask whether HRs show response patterns under Aims 1-3 that resemble Atts, thereby suggesting a diathesis towards suicide.