Psychobiology of Suicidal Behavior in Borderline Personality Disorder

描述（由申请人提供）：边缘型人格障碍（BPD）自杀行为的心理生物学研究是第一项针对BPD患者自杀行为的临床、心理社会和生物学风险因素的前瞻性研究。这项工作的首要目标是确定危险因素和临床亚型预测医学上严重的自杀行为。BPD是一种高度流行的精神疾病，在高达2%的人口中发现，并且是唯一的精神疾病，部分定义为反复自杀企图。BPD的自杀完成率为3%-10%，是自杀研究的临床相关模型。这项研究遵循自杀行为的压力素质模型，该模型预测当人际危机和抑郁等急性压力源与冲动或情感不稳定等人格特征相互作用时，自杀风险会增加。这些人格特征是由特殊的大脑网络介导的，并有助于在压力下自杀的生物素质。在摄入时，受试者参与与自杀行为相关的风险因素的多维评估。然后在3个月、6个月和每年进行系统随访，以确定短期（12个月）、中期（2-4年）和长期（6+-10+年）随访间隔内自杀行为的前瞻性预测因素。目前，入组了245例BPD受试者，追踪率为92%。在2年的随访中，25%的受试者再次尝试自杀。使用轨迹分析，高致死性BPD亚型已被定义为增加其反复尝试的致命性。最近完成的一项对90名受试者的6年随访分析发现，在所有时间间隔内，心理社会功能不良是自杀行为最一致的预测因素。该提案将增加100例额外的BPD受试者和5年随访，以增加我们在所有时间间隔（特别是长期时间间隔）分析的统计功效，因为许多受试者将进入自杀风险最高的年龄。增加了额外的评估来表征生活质量、诊断稳定性和核心维度特征，因为这些变量会影响心理社会和自杀结局。本研究还使用fMRI方案调查了自杀行为的神经生物学素质，特别针对对应激反应至关重要的调节功能的神经基础（例如，反应抑制、冲突解决和自传体记忆）。一个特定的神经网络被提出作为自杀行为的中介。功能磁共振成像协议将测试在负情感刺激过程中，该神经网络中关键结构的功能连接。初步研究表明，负性情感刺激对这些重要的调节功能的认知加工产生干扰。情感干扰会增加自杀行为的风险。纵向研究的结果可立即用于指导自杀风险评估和治疗策略;而fMRI子研究可提供识别自杀风险最高的患者的生物标志物，以及跟踪治疗进展的非侵入性方法。

DESCRIPTION (provided by applicant): Psychobiology of Suicidal Behavior in Borderline Personality Disorder (BPD) is the first prospective study of clinical, psychosocial and biological risk factors for suicidal behavior in patients with BPD. The overarching goal of this work is to identify risk factors and clinical subtypes predictive of medically serious suicidal behavior. BPD is a highly prevalent psychiatric disorder, found in up to 2% of the population, and is the only psychiatric disorder defined, in part, by recurrent suicide attempts. With a suicide completion rate of 3%-10%, BPD is a clinically relevant model for the study of suicide. This study follows the stress-diathesis model of suicidal behavior, which predicts an increase in risk of suicide when acute stressors, such as interpersonal crises and depression, interact with personality traits such as impulsivity or affective instability. These personality traits are mediated by speciic brain networks and contribute a biologic diathesis to suicide under stress. At intake, subjects participate in a multidimensional assessment of risk factors associated with suicidal behavior. Systematic follow-ups are then conducted at 3 months, 6 months, and annually to define prospective predictors of suicidal behavior in short term (12 month), intermediate (2-4 years) and long term (6+-10+ years) follow-up intervals. Currently, 245 BPD subjects are enrolled, with a 92% trace rate. By 2 year follow-up, 25% of subjects re-attempted suicide. Using trajectory analysis, a High Lethality BPD subtype has been defined by the increasing lethality of their recurrent attempts. A recently completed 6 year follow-up analysis of 90 subjects identified poor psychosocial function as the most consistent predictor of suicidal behavior across all time intervals. This proposal will add 100 additional BPD subjects and 5 years of follow-up to increase statistical power of our analyses in all intervals, especially the long-term interval, whe many subjects will enter the age of highest risk for suicide. Additional assessments have been added for characterizing quality of life, stability of diagnosis and core dimensional traits, as these variables impact both psychosocial and suicidal outcomes. This study also investigates the neurobiologic diathesis to suicidal behavior using fMRI protocols, specifically targeting the neural basis of regulatory functions critical in responding to stress (e.g., response inhibition, conflict resolution, & autobiographic memory). A specific neural network is proposed as a mediator of suicidal behavior. fMRI protocols will test the functional connectivity of key structures in this neural network during negative affective stimulation. Preliminary studies indicate that negative affective stimulation produces interference with cognitive processing in these important regulatory functions. Affective interference increases the risk of suicidal behavior. The results of the longitudinal studies are immediately applicable to guide suicide risk assessment and treatment strategies; while the fMRI substudy may provide a biomarker identifying patients at highest risk for suicide, and a non-invasive method for following the progress of treatment.