Affective & Neurobiological Predictors of Adolescent-Onset Alcohol Use Disorders

描述(由申请人提供)： 尽管几十年来一直有研究将抑郁症和酒精使用障碍(AUD)联系起来，但我们对其共同病因的了解仍然不足，特别是在青春期出现它们的重要性，青春期是AUD的易感性增加的时期。本应用描述了一项关于青春期AUD发病的情感和神经生物学危险因素的研究。这项研究的目的是：1)确定发病前的情感、神经生物学、遗传和环境因素之间的主要影响和相互作用，因为它们与AUD的发展风险有关；2)确定这些因素的哪些组合可以预测AUD在青春期的最终发展；以及3)检查AUD对青少年大脑发育的影响。该设计的目的是理清这些风险因素如何参与AUD的发展，而这些风险因素受到先前存在的抑郁风险的影响。这将通过选择两个样本来实现，这些青少年在初次评估时年龄在12岁至14岁之间，他们的家庭负担要么高要么低，并在青春期后期的三年内每年对他们进行跟踪调查。措施将包括：情绪和负面情绪的评估；为情感行为服务的神经回路的功能成像；与5-羟色胺神经传递有关的基因多态；暴露于急性/慢性应激源；以及酒精使用和障碍的维度评估。这项工作的短期目标是了解抑郁症和AUD之间的病因学联系，并最终了解它们在青春期的出现。长期目标是以有助于早期干预和预防战略的方式确定参与发展的途径和机制。

DESCRIPTION (provided by applicant): Despite decades of research linking depression and alcohol use disorders (AUD), our understanding of their shared etiologies remains understudied, especially the importance of their emergence during adolescence, a period of increased susceptibility for AUD. This application describes a study of affective and neurobiological risk factors for the onset of AUD during adolescence. The aims of the study are to: 1) Identify the main effects and interactions among premorbid affective, neurobiological, genetic, and environmental factors as they relate to the risk to develop AUD; 2) Determine which combinations of these factors predict the eventual development of AUD during adolescence; and 3) Examine the consequences of AUD on adolescent brain development. The design is aimed at disentangling how these risk factors are involved in the development of AUD moderated by preexisting risk for depression. This will be accomplished by selecting two samples of adolescents, aged 12 to 14 years at the time of initial assessment, who have either high or low familial loading for depression and following them annually over a three year period into late adolescence. Measures will include: the assessment of mood and negative affect; functional imaging of neural circuitry subserving affective behaviors; genetic polymorphisms involved in serotonin neurotransmission; exposure to acute/chronic stressors; and dimensional assessments of alcohol use as well as disorders. The short-term goals of this work are to understand the etiologic links between depression and AUD and ultimately their emergence during adolescence. The long-term goals are to identify pathways and mechanisms involved in the development of AUD in ways that will inform early intervention and prevention strategies.