PSYCHOBIOLOGY OF SUICIDAL BEHAVIOR IN BORDERLINE PERSONALITY DISORDER

这一竞争性的更新建议扩展和丰富了我们对自杀行为的纵向调查， 边缘型人格障碍（BPD），特别关注医学上严重的自杀行为。我们的工作取得 日期点的核心作用，社会情绪素质自杀的BPD。在这组患者中， 在过去15年多的BPD（以及其他自杀相关研究）中，我们发现（i） 消极情感和攻击性强有力地预测自杀行为，（ii）社会情绪影响破坏 额叶边缘系统的大脑活动，使BPD的认知控制，以及（iii）自杀行为与 社会和非社会决策中的行为和神经计算改变。拟议 研究建立在临床理论和实验数据的基础上， 过度敏感，经常扭曲社交线索，形成他人的极端观点，并错误归因 恶意感知到的拒绝、遗弃或背叛会引发攻击性和负面情绪。 可能导致自杀危机的反应。为了进一步解释这种升级的机制，我们 我将测试一个概念模型，该模型从巴甫洛夫的角度看待对社会压力的适应不良反应。 干扰目标导向的决策过程。因此，我们将测试总体假设，在一个 人际背景下，情感上强有力的线索掩盖了患者对战略目标的表述， 扭曲了他们行为的预期价值。这项工作连接了三个分析单元： 在我们的高风险队列中，高致命性自杀企图是我们先前研究的重点（目标1;介于- 社会情绪素质在日常生活中对自杀行为的行为和情感特征 通过经验采样捕获（目标2;人内）;和适应不良的社会神经基础 通过增强学习计算模型增强的功能性MRI评估决策 (Aim（3）人。持续研究该BPD队列的一个关键优势， 自杀行为的高风险是，许多参与者现在正进入中年，当冲动的自杀行为 自杀率降低，但严重自杀行为的风险增加。这也是一个过渡时期， 目标2和3的纵向研究在工作中引入了重大创新，并引入了新的研究者 在自杀风险（Dombrovski，Szanto）、BPD和经验抽样（Hallquist，Pilkonis， Wright）、成像和计算建模（Dombrovski，Hallquist）以及定量方法（Hallquist， Wright）。拟议的研究解决了自杀优先研究议程的第一个问题 预防，为什么人们会自杀？预测误差的神经计算结构（在社会 目标3中评估的期望值直接反映了研究领域标准的框架 （RDoC），以及我们的概念和分析工作，以桥接分析单元。这项工作将开辟新的途径 发现行为、情感和神经标记，阐明接近自杀行为的过程。

This competitive renewal proposal extends and enriches our longitudinal investigation of suicidal behavior in borderline personality disorder (BPD), focusing specifically on medically serious suicidal acts. Our work to date points to the central role of a socio-emotional diathesis to suicide in BPD. In this cohort of patients with BPD ascertained over the previous 15+ years (and other related studies of suicide), we have found that (i) negative affectivity and aggression robustly predict suicidal behavior, (ii) that socio-emotional influences disrupt fronto-limbic brain activity subserving cognitive control in BPD, and (iii) that suicidal behavior is associated with behavioral and neurocomputational alterations in social and non-social decision-making. The proposed research builds on clinical theory and experimental data that characterize BPD patients as interpersonally hypersensitive, often distorting social cues, forming extreme opinions of others, and misattributing malevolence. Perceived rejection, abandonment, or betrayal trigger aggression and negative emotional responses that can lead to a suicidal crisis. To explicate further the mechanisms underlying this escalation, we will test a conceptual model that views maladaptive responses to social stressors in terms of Pavlovian interference with goal-directed decision processes. We will thus test the overarching hypothesis that, in an interpersonal context, emotionally potent cues overshadow patients’ representations of strategic goals and distort the expected value of their actions. This work bridges three units of analysis: prospective predictors of high-lethality suicide attempts in our high-risk cohort, the focus of much of our prior research (Aim 1; between- persons); behavioral and affective signatures of the socio-emotional diathesis to suicidal behavior in daily life captured via experience sampling (Aim 2; within-person); and neural underpinnings of maladaptive social decision-making assessed by functional MRI augmented with a reinforcement learning computational model (Aim 3; within-person). A key strength of continuing work with this BPD cohort with a longitudinally ascertained high risk of suicidal behavior is that many participants are now entering midlife, when impulsive suicidal acts become less common, but the risk of serious suicidal acts increases. This is also a time of transition for our longitudinal study with Aims 2 and 3 introducing significant innovation into the work and with new investigators contributing expertise in suicide risk (Dombrovski, Szanto), BPD and experience sampling (Hallquist, Pilkonis, Wright), imaging and computational modeling (Dombrovski, Hallquist), and quantitative methods (Hallquist, Wright). The proposed study addresses the #1 question of the Prioritized Research Agenda for Suicide Prevention, Why do people become suicidal? Neurocomputational constructs of prediction error (in a social context) and expected value assessed in Aim 3 directly reflect the framework of the Research Domain Criteria (RDoC), as do our conceptual and analytic efforts to bridge units of analysis. This work will open new avenues for discovery of behavioral, affective, and neural markers elucidating processes proximal to the suicidal act.