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

在过去的十年里，描述和治疗精神障碍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的神经机制。例如，相对于健康志愿者，患有严重抑郁障碍(MDD)的人 可能显示与认知控制有关的大脑系统活动不足(例如背侧和腹外侧部 前额叶皮质，dIPFC和vIPFC)和系统的过度激活与触发情绪有关 反应(例如杏仁核)。特别令人感兴趣的是这些模式可能在多大程度上与 只是对MDD，但对与抑郁发作相关的自杀风险。尽管到目前为止还没有什么功能性的 康特中心实验室的PET和尸检工作表明，成像数据已经解决了这个问题 腹外侧PFC和前扣带回功能低下，以及较低的5-羟色胺转运体结合 杏仁核和腹侧/眼眶PFC可能导致自杀或非致命性自杀未遂。这 Proposal试图澄清这些联系，建立在认知控制情绪的新兴模型基础上 健康成年人检查情绪调节的特定认知策略的神经基础--称为 重新评估-在有自杀未遂的严重抑郁障碍患者(MDD-ATTS)中， 从未试图自杀(MDD-非ATTS)、健康志愿者(HV)和目前未患抑郁症的成年人 MDD-Atts的后代可能有更高的自杀风险(HRs)。在目标1-3中，我们将比较神经 MDD-Atts、MDD-Non-Atts和HV的重新评估绩效的相关性以确定是否抑郁 一般个人，特别是那些企图自杀的人(目标1)会产生更强的负面影响 情绪或有更大的困难下调它们，(目标2)产生较弱的积极情绪或有 更大的麻烦--上调它们，或者在目标1和目标2下表现出与监管相关的活动模式 (探索性目标3)与5-羟色胺功能异常(见P3)、童年逆境、压力有关 反应能力和/或攻击性(见CEC)。在探索性目标4中，我们询问人力资源是否显示出响应 目标1-3下的图案类似于Atts，因此暗示有自杀的素质。

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.