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研究酒精依赖（AD）发展过程中的转变，因为它们与女性外化障碍的风险有关。目前的研究将AD发病的发育方法与双胞胎模型结合起来，以估计遗传和环境对外部性疾病的影响以及发展到更严重饮酒的速度。该研究扩展了关于AD和外化障碍及其共同责任的遗传影响的文献，从疾病发展的三个重要过渡阶段来检查AD：不使用到第一次酒精使用，第一次酒精使用到第一次酒精相关问题（即滥用或依赖症状）的发作，以及第一次酒精相关问题到AD发作。数据来自一项对青春期女性和女性酒精使用障碍和相关精神病理的纵向研究。样本包括来自密苏里州青少年女性双胞胎研究的3787对女性双胞胎。参与者报告了饮酒行为、AD症状和品行障碍（CD）症状，母亲报告了对立违抗障碍（ODD）症状。从a)未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阿尔茨海默病的转变的方差来源将首先进行建模。然后，这些基本模型将被扩展，以评估在三变量模型中跨阶段过渡到更严重饮酒状态的共同与独特的遗传和环境贡献。反映乳糜泻和ODD症状的综合外化因素将被划分为遗传因素和环境因素。接下来，外化因素将被整合到三个阶段转变的三变量模型中，以确定外化疾病在AD发展过程中所带来的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。除了为阿尔茨海默病发展的病因学模型提供信息外，对阿尔茨海默病发展过程中多个阶段进展的风险来源进行评估，对于制定与发展相适应的预防和干预措施至关重要。通过确定AD过程中的过渡点，a)环境影响在疾病进展中发挥更大作用，b)外化障碍与酒精使用行为最密切相关，研究结果将把预防工作指导到酒精使用过程中结果最容易改变的阶段。

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.