Cognitive Phenotype Neural Circuitry in Vivo In Mood Disorders and Suicidal Behavior

摘要--项目4 我们如何应对负面事件，调节我们对它们的反应，以及后来如何记住它们--发挥着重要作用 在情绪和/或焦虑症(如抑郁症)中起核心作用，并可能导致个人参与自我 破坏性行为，包括自杀。因此，研究的一个关键问题是什么是心理学和 神经机制产生我们对厌恶事件的初始反应，将该事件编码到记忆中，然后 使我们能够规范我们对它的反应。在本供资期间，我们通过以下方式开始处理这些问题 研究MDD、自杀风险和反应的产生和调节之间的关系 正常的消极和积极的刺激。在这次更新中，有三个因素指导我们继续关注负面 情绪反应和调节，以及对记忆的新关注。首先，在当前的资助期内，我们 研究发现，对厌恶刺激的反应与收集的临床相关变量关系最密切 PS 1、3和5。第二，捕捉可能与以下内容相关的自我相关的负面反应 自杀风险，我们开发了一种新的情绪调节任务，包括回忆不愉快 自传式记忆和飞行员数据发现，它对MDD和对照组的差异很敏感 杏仁核和海马体的功能。第三，众所周知，慢性压力会影响PFC的结构完整性 和海马区通过HPA轴的激活和神经炎症，而尸检的P1数据已经确定了这一点 自杀死者的变化。鉴于这些数据，在这个提案中，我们重点研究MDD和自杀是如何 在以下背景下，风险与PFC、杏仁核和海马体系统有关：(目标1)回忆和 调节对厌恶的自传体记忆的反应，(目标2)产生持久的负面情绪 可能会延续到随后的中性体验和颜色记忆的状态，以及理解 在项目3和项目5下收集的临床和生物变量的个体差异如何与数据相关 在目标1和目标2下收集。

SUMMARY – PROJECT 4 How we respond to negative events, regulate our responses to them, and later remember them – plays a central role in mood and/or anxiety disorders, such as depression, and can lead individuals to engage in self- destructive behaviors, including suicide. As such, a critical question for research is what psychological and neural mechanisms generate our initial response to an aversive event, encode that event into memory, and enable us to regulate our response to it. In the current funding period, we began addressing these issues by examining the relationship between MDD, suicide risk, and the generation and regulation of responses to normatively negative and positive stimuli. In this renewal, three factors guide our continued focus on negative emotional reactivity and regulation as well as a new focus on memory. First, in the current funding period we found that responses to aversive stimuli were most strongly related to clinically relevant variables collected in Ps 1, 3 and 5. Second, to capture idosyncratically self-relevant negative responses that may be relevant to suicide risk, we developed a novel variant of our emotion regulation task that involved recollecting unpleasant autobiographical memories and in pilot data found that it was sensitive to MDD vs. control differences in amygdala and hippocampal function. Third, chronic stress is known to impact structural integrity of the PFC and hippocampus via HPA axis activation and neuroinflammation, and postmortem P1 data has identified such changes in suicide decedents. Given these data, in this proposal we focus on studying how MDD and suicide risk are related to PFC, amygdala and hippocampal systems, in the context of: (Aim 1) recollecting and regulating responses to aversive autobiographical memories, (Aim 2) generating enduring negative emotional states that may carry over to subsequent neutral experiences and color memory for them, and understanding how individual differences in clinical and biological variables collected under Projects 3 and 5 relate to data collected under Aims 1 and 2.