Stress, Inflammation, Aggression and Emotion Regulation in Suicidal Behavior

摘要--项目5 Conte中心项目5调查自杀行为的压力-素质模型。具体来说，我们检查了 使用Trier社会压力测试(TSST)的压力反应和日常生活的生态瞬时评估 应激源(EMA)，并研究了童年逆境(CA)和冲动性攻击在抑郁症自杀中的作用 尝试者、抑郁的不尝试者和健康的志愿者。我们发现，虽然攻击性在 在尝试者中，应激反应性只有在具有高反应性/冲动性攻击的尝试者中才会增强。我们 还观察到，这些高度应激反应、冲动的群体表现出一系列特征：一种模式 与CA病史相关的频繁的短暂的、高度可变的自杀意念(SI)，并在反应中增加 对日常压力源，以及较差的情绪调节。相比之下，我们发现高度计划的自杀 自杀未遂与家族自杀史和持续性SI有关。因此，我们观察到不同组的 在从非常冲动到高度冲动的连续体的两端与自杀结果相关的特征 有计划和故意的自杀行为。在此应用程序中，我们通过进一步探索 自杀企图冲动/计划的神经生物学和认知基础。具体来说，我们将 检查执行功能和情绪调节策略(在TSST和EMA期间的体内)和 确定它们与自杀行为、SI变异性和应激反应的关系。第二个有希望的人 我们工作的延伸是研究相关的应激反应机制，特别是炎症，这是 与CA和攻击性的自杀危险因素相关。我们已经证明了细胞因子激活的犬尿氨酸 途径在尝试者中上调，抗炎多不饱和脂肪酸水平较低 (多不饱和脂肪酸)二十二碳六烯酸可以预测自杀企图，我们有高风险的IL-6升高的试点数据 与以前的文献一致。对行为和生理途径的更清晰的描述 自杀行为将通过根据风险确定更个性化的方法来改进预防 侧写。

SUMMARY – PROJECT 5 Conte Center Project 5 investigates the stress-diathesis model of suicidal behavior. Specifically, we examined stress response using the Trier Social Stress Test (TSST) and Ecological Momentary Assessment of daily stressors (EMA), and studied the role of childhood adversity (CA) and impulsive aggression in depressed suicide attempters, depressed nonattempters and healthy volunteers. We found that while aggression was higher in attempters, stress responsivity was heightened only in attempters with high reactive/impulsive aggression. We also observed that this highly stress responsive, impulsive group displayed a cluster of characteristics: a pattern of frequent brief, highly variable suicidal ideation (SI) that correlated to a history of CA and increased in response to daily stressors, together with poorer emotion regulation. In contrast, we found that high planning of suicide attempts was related to family history of suicide and persistent SI. Thus, we observe different sets of characteristics associated with suicidal outcomes at opposite ends of a continuum from very impulsive to highly planned and deliberate suicidal behaviors. In this application, we expand our work by further exploring the neurobiological and cognitive underpinnings of impulsivity/planning of suicide attempts. Specifically, we will examine executive functioning and emotion regulation strategies (in vivo during the TSST and EMA) and determine their relationships with suicidal behavior, SI variability and stress response. A second promising extension of our work is to study related stress response mechanisms, particularly inflammation, which is associated with suicide risk factors of CA and aggression. We have shown that the cytokine-activated kynurenine pathway is upregulated in attempters, and that lower levels of the anti-inflammatory polyunsaturated fatty acid (PUFA) docosahexaenoic acid predict suicide attempts, and we have pilot data on elevated IL-6 in high risk attempters, consistent with previous literature. A clearer delineation of the behavioral and physiological pathways to suicidal behavior will improve prevention by identifying a more personalized approach depending on the risk profile.