Impulsive Aggression, Neurocognition, and Suicidal Behavior in Depressed Youth

描述(申请人提供)：严重抑郁障碍(MDD)是青少年自杀行为最有效的精神危险因素，但大多数抑郁青年从未试图自杀，削弱了MDD诊断在评估未来自杀行为风险方面的积极预测价值。更深入地了解抑郁症青年自杀行为的前兆和途径，特别是如果这些知识有助于制定有效的风险评估和干预战略，将大大有助于预防青年自杀的努力。了解抑郁症青少年未来自杀企图的可测量因素对于预防青少年自杀的努力至关重要，因为：1)帮助认识到自杀风险特别高的抑郁症青少年，他们至少可能需要更密切的监督和遏制；2)确定情绪障碍本身以外的临床干预目标；以及3)有助于开发有关评估工具和风险标记物，以便更好地评估个人自杀风险，并为有自杀风险的青少年的临床干预研究提供信息。由早期研究人员(ESI)提出的R01应用程序将通过检查冲动性攻击和神经认知功能在患有MDD的青少年自杀行为的病因中的作用来解决知识的关键差距。中心假设是冲动的攻击性和执行功能和决策的缺陷将在很大程度上促进未来自杀企图的模型，并为传统的评估方法增加积极的预测价值。我们的假设是由有希望的试点工作提供的，在这些工作中，冲动攻击性和决策缺陷的测量明显区分了抑郁的青少年自杀未遂者和非自杀未遂者。这项设计包括横断面比较，以及对300名有和没有自杀未遂史的抑郁青年进行前瞻性纵向研究，从青春期早期到青春期中期，这是自杀行为风险最高的发育期。这些结果将有助于NIMH的使命，通过提高我们识别MDD青少年未来自杀行为的时间和可能的因果顺序的能力，从而为实际的临床风险评估、干预和自杀行为的预防制定目标。 公共卫生相关性：青少年自杀行为的严重后果使准确识别高危青年成为重要的临床、研究和公共卫生目标。这是首次对青少年自杀行为的发展前置因素进行的大规模前瞻性研究，以全面解决抑郁青年中的多种危险和保护因素。通过使用一种多方法、最先进的和试点测试的方法来评估冲动性攻击行为，以及信息量丰富的计算机化的执行功能和决策制定子测试，拟议的研究可能有助于澄清自杀行为病因的具体行为和神经认知途径。因此，这项工作有可能为开发实用的自杀风险评估工具、基于经验的治疗和预防性干预提供信息，以减少青少年自杀。

DESCRIPTION (provided by applicant): Major Depressive Disorder (MDD) is the most potent psychiatric risk factor for suicidal behavior in adolescents, yet most depressed youth never attempt suicide, diminishing the positive predictive value of a diagnosis of MDD in gauging the risk of future suicidal acts. Efforts to prevent youth suicide would benefit greatly from a deeper understanding of precursors and pathways to suicidal behavior in depressed youth, particularly if such knowledge informs the development of effective risk evaluation and intervention strategies. Knowledge of measurable factors that increase the risk of future suicide attempts in depressed adolescents could prove critical to efforts to prevent youth suicide by virtue of: 1) aiding in the recognition of depressed youth at especially heightened risk for suicide, who at a minimum may require closer supervision and containment; 2) identifying targets for clinical intervention beyond the mood disorder per se; and, 3) contributing to the development of assessment tools and risk markers relevant to better gauging individual suicide risk and informing clinical intervention research with youth at risk for suicide. The proposed R01 application from an early stage investigator (ESI) will address critical gaps in knowledge by examining the role of impulsive aggression and neurocognitive functioning in the etiopathogenesis of suicidal behavior in adolescents with MDD. The central hypothesis is that impulsive aggression and deficits in executive function and decision making will contribute substantially to a model of future suicide attempts and add positive predictive value to traditional assessment approaches. Our hypothesis is informed by promising pilot work in which measures of impulsive aggression and decision making deficits sharply distinguished depressed adolescent suicide attempters from non-attempters. The design includes cross-sectional comparisons as well as a prospective longitudinal study of 300 depressed youth with and without a prior history of suicide attempt, followed from early to middle adolescence, the developmental period of highest risk for suicidal behavior. These results will contribute to the mission of the NIMH by improving our capacity to identify the temporal and likely causal sequence of antecedents to future suicidal acts in youth with MDD, thus framing targets for practical clinical risk assessment, intervention, and the prevention of suicidal behavior. PUBLIC HEALTH RELEVANCE: The severe consequences of adolescent suicidal behavior make the accurate identification of youth at high risk an important clinical, research, and public health objective. This is the first large-scale prospective study of the developmental antecedents of adolescent suicidal behavior to comprehensively address multiple risk and protective factors in depressed youth. With the use of a multi-method, state-of-the-art, and pilot tested approach for assessing impulsive aggression and an informative computerized battery of subtests of executive function and decision making, the proposed research may help to clarify the specific behavioral and neurocognitive pathways contributing to the etiopathogenesis of suicidal behavior. Thus, this work has the potential to inform the development of practical suicide risk evaluation tools, empirically-based treatments, and preventive interventions to reduce adolescent suicide.