Affective & Neurobiological Predictors of Adolescent-Onset Alcohol Use Disorders

描述（由申请人提供）： 尽管数十年的研究将抑郁症和酒精使用障碍（AUD）联系起来，但我们对它们共同病因的理解仍然不足，特别是它们在青春期出现的重要性，这是AUD易感性增加的时期。本申请描述了一项关于青春期AUD发病的情感和神经生物学风险因素的研究。该研究的目的是：1）确定发病前情感，神经生物学，遗传和环境因素之间的主要影响和相互作用，因为它们与发展AUD的风险有关; 2）确定这些因素的哪些组合预测青春期AUD的最终发展;和3）检查AUD对青少年大脑发育的后果。该设计的目的是解开这些风险因素是如何参与AUD的发展，由预先存在的抑郁风险调节。这将通过选择两个样本的青少年，年龄在12至14岁的初始评估时，谁有高或低的抑郁症的家庭负荷，并遵循他们每年超过三年的时间到青春期后期。措施将包括：情绪和负面影响的评估;神经回路的功能成像，使情感行为;参与5-羟色胺神经传递的遗传多态性;暴露于急性/慢性应激源;以及酒精使用和精神障碍的维度评估。这项工作的短期目标是了解抑郁症和AUD之间的病因联系，并最终在青春期出现。长期目标是确定参与AUD发展的途径和机制，以便为早期干预和预防策略提供信息。

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.