Impulsivity and Biological Markers for Suicidality and Drug Use in Adolescents

描述（由申请人提供）：虽然横断面研究表明药物滥用、冲动、血清素失调和压力生活事件与自杀有关，但有关这些因素之间具体关系的数据有限。最近一个由nida赞助的工作组发现了这些文献中的空白，确定了未来研究的优先事项，并呼吁进行以下研究：(A)冲动在自杀行为和药物滥用中的作用；(b)生物机制（如基因-环境相互作用）如何预测这些关系；(c)自杀行为和药物滥用之间的纵向关系。研究通常将冲动性或5-羟色胺（5-HT）标记的个体测量与先前自杀行为和药物滥用的自我报告横断面联系起来，但他们还没有确定这些测量在确定未来药物滥用和自杀行为方面的预测有效性。此外，冲动行为和5-羟色胺之间的关系，虽然经常被包括在自杀理论中，但还没有得到牢固的确立。此外，尚不清楚这些模型中定义的因素（例如，冲动性，5-HT和压力生活事件）的组合如何影响药物滥用和自杀行为的发展轨迹。本研究旨在探讨高风险青少年的冲动性、5-HT、生活压力事件与吸毒和自杀行为之间的相互关系。我们的目标是确定这些因素对自杀行为和药物滥用的发展轨迹的直接和相互作用的贡献。四个具体目标是：(1)确定住院前自杀和药物使用行为的自我报告历史与行为冲动、压力生活事件和基线测量的5-HT标志物之间的关系；(2)建立行为冲动、压力生活事件和5-HT标记（包括个体和相互作用）对未来自杀和药物使用行为的预测效度；(3)利用潜在类模型识别自杀和药物使用行为的不同类型和轨迹，并确定这些轨迹所定义的群体在行为冲动、压力生活事件和5-HT功能方面的差异；(4)利用一个领先的自杀模型的理论框架，确定冲动、压力生活事件、5-HT功能和药物使用对自杀行为的相对贡献，并确定这些关系的方向性，同时调整其他已知的危险因素。与公共卫生相关：从这项前瞻性纵向研究中获得的知识将为有和没有自杀行为和药物滥用的青少年的状态和特征特征以及5-HT标记提供见解，这将使我们能够在这一异质高危人群中区分发育亚群。反过来，这些知识将被用来为有自杀和药物使用行为的青少年的治疗和预防计划的未来发展提供信息，并将允许设计多种治疗方法，考虑到不同发展亚群体的具体需求。

DESCRIPTION (provided by applicant): While cross-sectional studies show that drug abuse, impulsivity, serotonin dysregulation, and stressful life events are associated with suicide, data regarding the specific relationships among these factors are limited. A recent NIDA-sponsored workgroup identified gaps in this literature, set priorities for future research, and called for studies examining: (a) the role of impulsivity in suicidal behaviors and drug abuse; (b) how biological mechanisms (e.g., gene-environment interactions) predict these relationships; and (c) how suicidal behaviors and drug abuse interrelate longitudinally. Studies have typically related individual measures of impulsivity or serotonin (5-HT) markers to self-reports of previous suicidal behaviors and drug abuse cross-sectionally, but they have not determined the predictive validity of these measures in determining future drug abuse and suicidal behaviors. Furthermore, the relationships between impulsive behavior and 5-HT, while often included in theories of suicide, have not been firmly established. Additionally, it is not known how the combination of factors (e.g., impulsivity, 5-HT, and stressful life events) defined within these models affects the developmental trajectories of drug abuse and suicidal behaviors. The purpose of this longitudinal study is to examine the interrelationships among impulsivity, 5-HT, stressful life events and the outcomes of drug use and suicidality in high-risk adolescents. Our goal is to determine the direct and interactive contributions of these factors to the developmental trajectories of suicidal behavior and drug abuse. The four specific aims are to: (1) determine how self-reported histories of suicidal and drug use behaviors prior to hospitalization relate to behavioral impulsivity, stressful life events, and 5-HT markers measured at baseline; (2) establish the predictive validity of behavioral impulsivity, stressful life events, and 5-HT markers (both individually and their interaction) for determining future suicidal and drug use behaviors; (3) identify distinct types and trajectories of suicidal and drug use behaviors (using latent class modeling), and determine how groups defined by these trajectories differ in behavioral impulsivity, stressful life events, and 5-HT function; and (4) determine the relative contributions of impulsivity, stressful life events, 5-HT function, and drug use to suicidal behaviors using the theoretical framework of a leading model of suicide, and to determine the directionality of these relationships while adjusting for other known risk factors. Relevance to Public Health: Knowledge gained from this prospective longitudinal study will provide insights into the state and trait characteristics, and the 5-HT markers of adolescents with and without suicidal behaviors and substance abuse, that will enable us to distinguish developmental subgroups within this heterogeneous, high-risk population. In turn, this knowledge will be used to inform future development of treatment and prevention programs for youths with suicidal and drug use behaviors and will allow for multiple treatment approaches to be designed that take into account the specific needs of the various developmental subgroups.