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

情绪障碍和自杀行为中的体内认知表型神经回路

• 批准号: 10408796
• 负责人: KEVIN N OCHSNER
• 金额: $ 11.82万
• 依托单位: NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-19 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10408796
• 关键词: Address; Affective; Aggressive behavior; Amygdaloid structure; Anterior; Anxiety Disorders; Autopsy; Aversive Stimulus; Behavioral; Binding; Biological; Borderline Personality Disorder; Brain; Chronic stress; Clinical; Cognitive; Color; Data; Depression and Suicide; Disease; Down-Regulation; Emotional; Emotions; Episodic memory; Event; Exposure to; Feeling suicidal; Functional disorder; Funding; Future; Generations; Hippocampus (Brain); Hydrocortisone; Image; Impulsivity; Individual; Individual Differences; Lateral; Lead; Measures; Memory; Mental Depression; Modeling; Monoamine Oxidase A; Mood Disorders; Neurobiology; Patient Self-Report; Pattern; Phenotype; Play; Positron-Emission Tomography; Reaction; Regulation; Reporting; Research; Risk; Role; Sampling; Self Destructive Behavior; Stimulus; Stress; Suicide; Suicide attempt; System; Testing; Trier Social Stress Test; Variant; Work; biological adaptation to stress; brain dysfunction; clinically relevant; cognitive control; emotion regulation; experience; hypothalamic-pituitary-adrenal axis; in vivo; negative affect; negative emotional state; negative mood; neural circuit; neuroinflammation; neuromechanism; novel; psychologic; recruit; relating to nervous system; response; social stressor; stress reactivity; stressor; suicidal behavior; suicidal risk; suicide attempter; suicide model; trait

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.

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，然后记住它们-- 在情绪和/或焦虑症，如抑郁症中起中心作用，并可导致个体参与自我- 破坏性行为，包括自杀。因此，研究的一个关键问题是， 神经机制产生我们对厌恶事件的最初反应，将该事件编码到记忆中， 使我们能够规范我们对它的反应。在当前的资助期内，我们开始通过以下方式解决这些问题： 研究MDD、自杀风险与对抑郁症的反应的产生和调节之间的关系。 负性和正性的刺激。在这次更新中，有三个因素指导我们继续关注负面影响， 情绪反应和调节以及对记忆的新关注。首先，在当前的供资期内， 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，为了捕捉可能与以下内容相关的同形自相关的负面反应， 为了降低自杀风险，我们开发了一种新的情绪调节任务， 自传体记忆和试点数据发现，它是敏感的MDD与控制差异， 杏仁核和海马功能。第三，已知慢性压力会影响PFC的结构完整性 和海马通过HPA轴激活和神经炎症，和死后P1数据已经确定， 自杀者的变化。鉴于这些数据，在本提案中，我们重点研究MDD和自杀 风险与PFC，杏仁核和海马系统有关，在以下背景下：（目的1）回忆和 调节对令人厌恶的自传体记忆的反应，（目的2）产生持久的负面情绪 这些状态可能会延续到随后的中性体验和颜色记忆， 项目3和项目5中收集的临床和生物学变量的个体差异与数据的关系 在目标1和2下收集。