Psychobiology of Suicidal Behavior in Borderline Personality Disorder

边缘型人格障碍（BPD）自杀行为的心理生物学研究是首个针对BPD患者自杀行为的临床、社会心理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，占人口的2%，是唯一一种被反复自杀企图所定义的精神障碍。BPD的自杀完成率为3%-10%，是研究自杀的临床相关模型。该研究遵循自杀行为的压力素质模型，该模型预测了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定的大脑网络调节的，并有助于在压力下自杀的生物学素质。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。然后系统随访3个月、6个月和每年，以确定短期（12个月）、中期（2-4年）和长期（6+-10+年）随访间隔中自杀行为的预期预测因素。目前，已有245名BPD受试者入组，追踪率为92%。经过2年的随访，25%的受试者再次试图自杀。通过轨迹分析，高致死率BPD亚型被定义为他们反复尝试的致命性增加。最近完成的一项针对90名受试者的6年随访分析发现，在所有时间间隔内，不良的心理社会功能是自杀行为最一致的预测因素。本建议将增加100名BPD受试者，并进行5年的随访，以提高我们在所有时间间隔，特别是长期时间间隔的统计分析能力，因为许多受试者将进入自杀风险最高的年龄。由于这些变量会影响心理社会和自杀结果，因此增加了对生活质量特征、诊断稳定性和核心维度特征的额外评估。本研究还利用功能磁共振成像技术研究了自杀行为的神经生物学特性，特别是针对应激反应中关键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）。提出了一种特定的神经网络作为自杀行为的中介。fMRI协议将测试在负性情感刺激下该神经网络中关键结构的功能连通性。初步研究表明，负性情感刺激在这些重要的调节功能中对认知加工产生干扰。情感干扰会增加自杀行为的风险。纵向研究的结果立即适用于指导自杀风险评估和治疗策略；而fMRI亚研究可以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. PUBLIC HEALTH RELEVANCE: This first longitudinal study of suicidal behavior in Borderline Personality Disorder identifies prospective predictors and high lethality BPD subtypes associated with suicidal behavior in short term (12 month), intermediate (2-4 year) and long term (6-10 years) follow-up. An fMRI substudy assesses the neurobiologic vulnerability to suicidal behavior through protocols measuring the effects of negative emotion on neural networks involved in responding to stress. 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.