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

情绪障碍和自杀行为中的体内认知表型神经回路

基本信息

批准号：
8605256
负责人：
KEVIN N OCHSNER
金额：
$ 13.13万
依托单位：
NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-07-19 至 2018-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8605256
关键词：
Address Adult Adult Children Affect Aggressive behavior Amygdaloid structure Animals Anterior Autopsy Autoreceptors Binding Biological Markers Brain Brain region Characteristics Childhood Clinical Cognitive Corpus striatum structure Data Depressed mood Disease Disease susceptibility Disinhibition Dorsal Down-Regulation Emotional Emotions Family Functional Imaging Functional disorder Generations Image Impairment Individual Individual Differences Instruction Link Major Depressive Disorder Mental Depression Mental disorders Methods Midbrain structure Modeling Mood Disorders Neurobiology Onset of illness Opioid Outcome Pattern Performance Phenotype Positioning Attribute Positron-Emission Tomography Prefrontal Cortex Prevalence Preventive Intervention Recording of previous events Recruitment Activity Recurrence Regulation Relative (related person)Reporting Research Personnel Risk Risk Factors Sampling Serotonin Stress Suicide Suicide attempt System Techniques Testing Up-Regulation Work base biological adaptation to stress clinical Diagnosis cognitive control cognitive neuroscience comparison group depressive symptoms emotion regulation experience healthy volunteer high risk in vivo indexing interest monoamine mood regulation neural circuit neuromechanism neurotransmission offspring positive emotional state relating to nervous system research clinical testing response serotonin transporter suicidal suicidal behavior suicidal risk suicide attempter trait

项目摘要

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.

在过去的十年中，描述和治疗精神疾病的一种重要方法一直是认知神经科学技术来理解临床功能障碍的神经机制。例如，相对于健康的志愿者，患有严重抑郁症的人（MDD）可能显示出与认知控制有关的脑系统的过度激活（例如背和腹外侧前额叶皮层，DIPFC和VIPFC）以及与触发情绪有关的系统的过度激活响应（例如杏仁核）。特别有趣的是这种模式可能与之相关的程度只是为了MDD，但要自杀与抑郁发作有关的风险。虽然迄今为止的功能很少成像数据已经解决了这个问题，孔戴中心实验室的宠物和验尸工作已显示该腹外侧PFC和前扣带回功能障碍以及较低的5-羟色胺转运蛋白结合杏仁核和腹/轨道PFC可能会导致自杀或非致命自杀企图的风险。这提案旨在阐明这些链接，以一种新兴的情感认知控制模型为基础健康的成年人检查情绪调节特定认知策略的神经底座 - 称为重新评估 - 在试图自杀（MDD -ATTS）的重度抑郁症的人中从未尝试过自杀（MDD-NON-ATTS），健康志愿者（HVS）和目前不抑郁的成人 MDD-ATTS的后代可能有自杀风险较高（HRS）。在目标1-3中，我们将比较神经 MDD-ATTS，MDD-Nonatts和HVS的重新评估性能的相关性个人一般，尤其是自杀的人（目标1）会产生更强大的负面情绪或在下调它们的情况下遇到更大的麻烦，（目标2）产生较弱的积极情绪或有在目标1和2下显示与监管相关活动的模式更大的麻烦（探索目的3）与5-HT功能的异常有关（请参阅P3），儿童逆境，压力响应性和/或侵略性（请参阅CEC）。在探索性目标4中，我们询问HRS是否显示反应 AIM 1-3的模式类似于ATT，从而暗示着对自杀的素质。