Drinking Motives in Internalizing and Externalizing Pathways to Alcohol Misuse

 描述（由申请人提供）：这项拟议的博士前国家研究服务奖（NRSA）申请的主要目的是支持申请人的职业目标，即成为一名独立的研究人员，领导一项研究计划，以了解酒精滥用的遗传和环境病因学及其与内化（情绪，焦虑症）和外化（反社会行为，非法药物使用）精神病理学的交叉点。这一目标将通过申请人的三重培训目标来实现：1）获得酒精滥用（和相关结果）的表型专业知识; 2）开发方法技能，以阐明酒精滥用的复杂性质以及导致其的内化和外化途径;和3）培养职业和专业发展技能。拟议的培训计划的中心是通过个性化的指导，课程，高级统计培训，传播活动，以及主要是酒精滥用的统计和分子遗传学研究来发展申请人的科学能力。酒精滥用，包括酗酒和病理性使用，在大学生中很普遍，它与许多负面的公共卫生结果有关。尽管付出了巨大的努力，研究人员仍无法明确阐明酒精滥用背后的遗传和环境因素。对这一困难的一种解释是，酒精滥用的表型和潜在遗传结构是异质性的-也就是说，酒精滥用不是由一组单一的遗传或环境原因驱动的，但可能有许多不同的风险因素导致酒精滥用，这些因素在个体之间差异很大。饮酒动机（例如，饮酒以缓解负面情绪与饮酒以增强积极情绪）与酒精使用行为有很强的经验关联，并提出了一个明确的机制，不同的遗传和环境途径可能会影响酒精滥用。消极和积极的强化饮酒动机，分别与神经质和冲动，并反映了一个突出的类型学，分类为“内化”与“外化”酗酒者的图式。这项建议的主要目的是利用饮酒动机，以减少表型的复杂性，从而调查遗传和环境因素，有助于不同的途径酒精滥用，我们假设对应于内化和外化亚型。为了做到这一点，我们利用了一个大的（N = 9,890），纵向，前瞻性研究的大学生，涉及收集DNA样本和自我报告的表型数据的数据。这项研究设计允许在一个重要的发展时期调查酒精滥用的生物，心理和社会方面。迫切需要了解可能导致个人危险或病理性饮酒的各种途径，以减轻相关的代价高昂和有害的后果。

 DESCRIPTION (provided by applicant): The principal aim of this proposed pre-doctoral National Research Service Award (NRSA) application is to support the applicant's career goal of becoming an independent investigator leading a program of research to understand the genetic and environmental etiology of alcohol misuse and its intersection with internalizing (mood, anxiety disorders) and externalizing (antisocial behavior, illicit drug use) psychopathology. This aim will be achieved through the applicant's three-fold training goals: 1) obtaining phenotypic expertise in alcohol misuse (and related outcomes); 2) developing methodological skills to elucidate the complex nature of alcohol misuse and the internalizing and externalizing pathways leading to it; and 3) cultivating career and professional development skills. The proposed training plan centers on developing the applicant's scientific abilities through individualized mentorship, coursework, advanced statistical training, dissemination activities, and, principally, a statistical and molecular genetic study of alcohol misuse. Alcohol misuse, including binge drinking and pathological use, is widespread among college students, and it is associated with many negative public health outcomes. Despite substantial efforts, researchers have not been able to unequivocally elucidate the genetic and environmental factors underlying alcohol misuse. One explanation for this difficulty is that the phenotypic and underlying genetic architecture of alcohol misuse is heterogeneous - that is, alcohol misuse is not driven by a single set of genetic or environmental causes, but there may be many distinct sets of risk factors contributing to alcohol misuse that differ greatly between individuals. Motives for drinking (e.g. drinking to relieve negative emotions versus drinking to enhance positive emotions) have strong empirical associations with alcohol use behaviors and present a clear mechanism by which divergent genetic and environmental pathways may influence alcohol misuse. Negative and positive reinforcement drinking motives are related, respectively, to neuroticism and impulsivity, and mirror the schema of a prominent typology that categorizes "internalizing" versus "externalizing" alcoholics. The primary aim of this proposal is to utilize drinking motives to reduce phenotypic complexity and thereby investigate genetic and environmental factors contributing to diverging pathways to alcohol misuse, which we hypothesize correspond to internalizing and externalizing subtypes. To do this, we take advantage of data from a large (N = 9,890), longitudinal, prospective study of college students involving collection of both DNA samples and self-reported phenotypic data. This study design allows for investigation of biological, psychological, and social aspects of alcohol misuse across an important developmental period. There is a critical need to understand the diverse pathways that can lead individuals to risky or pathological alcohol use in order to alleviate the associated costly and harmful consequences.