Heritability of Transitions in Women's Alcohol Use/Dependence

描述（由申请人提供）：拟议项目的主要目的是检查酒精依赖（AD）发展过程中的过渡，因为它们与女性外部化疾病的风险有关。目前的研究整合了一个发展的方法，以双胞胎建模的AD发病，以估计遗传和环境的贡献外化障碍和进展到更严重的饮酒率。这项调查扩展了关于AD和外化障碍及其共同责任的遗传影响的文献，通过检查AD在疾病发展中的三个重要过渡阶段：不使用酒精到首次使用酒精，首次使用酒精到首次酒精相关问题的发作（即，滥用或依赖症状），以及AD发作前的首次酒精相关问题。数据来自一项关于青少年女性和女性酒精使用障碍及相关精神病理学的纵向研究。样本由来自密苏里州青少年女性双胞胎研究的3787名女性双胞胎组成。饮酒行为，AD症状和行为障碍（CD）症状由参与者报告，对立违抗性障碍（ODD）症状由母亲报告。最初将对从a）不使用到首次使用酒精，B）首次使用酒精到首次出现酒精问题，以及c）首次出现酒精问题到AD发作的转变中的方差来源进行建模。然后，这些基本模型将被扩展，以评估共同与独特的遗传和环境的贡献，以发展到一个更严重的饮酒状态跨阶段过渡的三变量模型。反映CD和ODD症状的复合外部因素将被划分为遗传和环境成分。接下来将外部化因素整合到三个阶段转换的三变量模型中，以确定外部化障碍引起的AD发展过程中风险的连续性以及这些跨阶段影响的遗传性。综合模型还将提供对外化障碍的遗传影响与酒精使用过渡的遗传影响相关程度的估计。 与公共卫生的相关性除了为AD发展的病因学模型提供信息外，估计AD发展过程中多个阶段进展的风险来源对于制定适合发展的预防和干预措施至关重要。通过确定AD过程中的过渡点，其中a）环境影响在疾病进展速度中发挥更大作用，B）外化障碍与酒精使用行为最密切相关，研究结果将指导预防工作，以达到最容易改变结果的酒精使用过程中的阶段。

DESCRIPTION (provided by applicant): The primary aim of the proposed project is to examine transitions in the course of alcohol dependence (AD) development as they relate to risk for externalizing disorders in women. The current study integrates a developmental approach to the onset of AD with twin modeling to estimate genetic and environmental contributions to externalizing disorders and to the rate of progression to more severe drinking. The investigation extends the literature on heritable influences on AD and externalizing disorders and their common liabilities by examining AD in terms of three significant transition stages in the development of the disorder: non-use to first alcohol use, first alcohol use to onset of first alcohol-related problem (i.e., abuse or dependence symptom), and first alcohol-related problem to onset of AD. Data are drawn from a longitudinal study of alcohol use disorders and associated psychopathology in adolescent females and women. The sample consists of 3787 female twins from the Missouri Adolescent Female Twin Study. Drinking behaviors, AD symptoms, and conduct disorder (CD) symptoms were reported by participants and oppositional defiant disorder (ODD) symptoms were reported by mothers. Sources of variance in the transitions from a) non-use to first alcohol use, b) first alcohol use to onset of first alcohol problem, and c) first alcohol problem to onset of AD, will initially be modeled. These basic models will then be expanded to assess common versus unique genetic and environmental contributions to progression to a more severe drinking status across stage transitions in a trivariate model. A composite externalizing factor reflecting CD and ODD symptoms will then be partitioned into genetic and environmental components. The externalizing factor will next be integrated into the trivariate model of the three stage transitions in an effort to determine the continuity of risk across the course of AD development posed by externalizing disorders and the heritability of those cross-stage influences. The integrated model will also provide an estimate of the extent to which heritable influences on externalizing disorders are correlated with heritable influences on the alcohol use transitions. Relevance to Public Health In addition to informing etiological models of AD development, estimation of the sources of risk for progression at multiple stages in the course of AD development is critical in the establishment of developmentally appropriate prevention and intervention efforts. By identifying transition points in the course of AD in which a) environmental influences play a larger role in the rate of progression of the disorder and b) externalizing disorders are most closely linked to alcohol use behaviors, findings will direct prevention efforts to stages in the course of alcohol use when outcomes may be most easily modified.