Psychobiology of Suicidal Behavior in Borderline Personality Disorder

描述(由申请人提供)：临界性人格障碍(BPD)自杀行为的心理生物学是对BPD患者自杀行为的临床、心理社会和生物学危险因素的第一项前瞻性研究。这项工作的首要目标是确定预测医学上严重自杀行为的危险因素和临床亚型。BPD是一种非常普遍的精神障碍，在高达2%的人口中发现，也是唯一的精神障碍，部分由反复自杀企图定义。BPD的自杀完成率为3%-10%，是研究自杀的一个具有临床意义的模型。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应激源与冲动或情感不稳定等个性特征相互作用时，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，并与应激下自杀的生物素质有关。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的随访，以确定在短期(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，245名BPD受试者登记在册，追踪率为92%。经过2年的随访，25%的受试者再次试图自杀。利用轨迹分析，高致死性BPD亚型已被定义为其反复尝试的日益致命的亚型。最近完成的一项对90名受试者的6年随访分析发现，心理社会功能差是所有时间段内自杀行为最一致的预测因素。这项建议将增加100名BPD受试者和5年的随访，以增加我们在所有时段的统计分析能力，特别是在许多受试者将进入自杀风险最高年龄的长期时段。增加了其他评估，以表征生活质量、诊断的稳定性和核心维度特征，因为这些变量影响心理社会和自杀结果。本研究还使用功能磁共振成像方法研究自杀行为的神经生物素质，特别是针对在应激反应中至关重要的调节功能(例如，反应抑制、冲突解决和自传记忆)的神经基础。提出了一种特定的神经网络作为自杀行为的中介。FMRI协议将测试负情感刺激期间这个神经网络中关键结构的功能连接性。初步研究表明，在这些重要的调节功能中，负性情感刺激会对认知过程产生干扰。情感干预会增加自杀行为的风险。纵向研究的结果立即适用于指导自杀风险评估和治疗策略；而功能磁共振成像亚研究可能提供一个识别自杀风险最高的患者的生物标志物，以及一种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.