The role of remission in the intergenerational transmission of alcohol use disorder: Course, context, and offspring outcomes

项目摘要 受影响的家庭所承受的经济、身体和情感伤害是巨大的。7.5万个美国小孩 与受AUD影响的父母一起生活，除了增加贫困，虐待和忽视的风险外， 酒精问题的遗传风险。AUDs的缓解很常见，但这很少被承认， 研究AUD的成本和后果。高达50%的人有终身AUD经验 缓解期，许多在AUD发作后14年内，许多在生育和养育子女的主要年龄。我们 该项目的广泛目标是全面探索缓解表型及其在治疗中的作用。 澳元的代际传递。我们将使用基于家庭的数据，从合作研究， 酒精中毒的遗传学，一项自1989年以来一直在进行的研究，招募了AUD风险较高的家庭， 超过15,000名饮酒者。由于COGA的高风险设计，有足够数量的澳元- 受影响的个体（N=7724，49%），因此可用于缓解，以允许进行缓解检查 家庭内部及其对后代结果的影响。在目标1中，我们将使用生存分析和以人为中心的 纵向方法来表征AUD和缓解（慢性AUD，稳定或复发）的过程 缓解，通过不同类型的缓解[禁欲，非禁欲]），并确定人口统计学 以及行为前因和缓解和复发的后遗症（婚姻状况，子女，就业， 收入、教育、同时发生的物质和精神障碍、治疗）。在探索性分析中，我们 构建缓解的家庭密度测量并检验其与AUD和缓解的关联。因为 影响AUD和缓解的遗传和环境因素并不完全重叠，我们预计这 测量与不发展AUD的概率和与 AUD个体缓解的可能性，与AUD的多基因风险（PRS）无关。在目标2中，我们使用 生物学上的父母-子女对来描述青少年子女的家庭环境（家庭 收入、父母婚姻状况、童年创伤）以及青少年和成年后代饮酒情况的变化 和作为亲本AUD/缓解的函数的AUD/缓解。兄弟姐妹之间的比较会显示出 父母缓解可能产生最大的影响，同时为潜在的遗传和 兄弟姐妹共有的环境混杂因素。该提案的创新之处在于它侧重于复原力，而不是 风险，在个人和家庭;在其影响的父母澳元/缓解到年轻和中期的延伸， 成年期;并在其使用的遗传知情的方法来了解缓解的作用， 澳元的代际传递。结果可以为临床医生提供杠杆，以鼓励恢复， 正在或计划成为父母并将有助于改善预防和治疗工作的患者， 减少AUD的代际传递和相关问题。

Project Summary Abstract The economic, physical and emotional harms borne by AUD-affected families are great. 7.5 million U.S. children live with an AUD-affected parent and have increased risk for poverty, abuse and neglect in addition to heightened genetic risk for alcohol problems. Remission from AUDs is common, but this is seldom acknowledged in research on the costs and consequences of AUDs. Up to 50% of individuals with lifetime AUDs experience remission, many within 14 years of AUD onset and many during prime child-bearing and child-rearing years. Our broad goal for this project is to comprehensively probe the remission phenotype and its role in the intergenerational transmission of AUDs. We will use family-based data from the Collaborative Study on the Genetics of Alcoholism, a study ongoing since 1989 that recruits families with heightened risk for AUDs and more than 15,000 ever-drinkers. Because of COGA's high-risk design, there are sufficient numbers of AUD- affected individuals (N=7724, 49%), and therefore available for remission, to permit this examination of remission within families and its effect on offspring outcomes. In Aim 1 we will use survival analysis and person-centered longitudinal methods to characterize the course of AUD and remission (chronic AUD, stable or relapsing remission, movement through different types of remission [abstinent, non-abstinent]) and identify demographic and behavioral antecedents and sequalae of remission and relapse (marital status, children, employment, income, education, co-occurring substance and psychiatric disorders, treatment). In exploratory analysis, we will construct a measure of family density of remission and test its association with AUD and remission. Because the genetic and environmental factors that influence AUD and remission do not entirely overlap, we expect this measure to have a small but significant association with the probability of not developing AUD and with the likelihood of remission in individuals with AUD, independent of polygenic risk (PRS) for AUD. In Aim 2, we use biological parent-offspring pairs to characterize the familial environment of adolescent offspring (household income, parental marital status, childhood trauma) and variation in adolescent and adult offspring alcohol use and AUD/remission as a function of parental AUD/remission. Sibling comparisons will delineate for whom parental remission is likely to have the greatest impact, while providing rigorous control for potential genetic and environmental confounders shared by siblings. The proposal is innovative in its focus on resilience, rather than risk, in individuals and families; in its extension of the influence of parental AUD/remission into young and mid- adulthood; and in its use of a genetically-informed approach to understanding the role of remission in the intergenerational transmission of AUDs. Results can provide leverage for clinicians to encourage recovery in patients who are or plan to become parents and will contribute to improved prevention and treatment efforts to reduce the intergenerational transmission of AUDs and associated problems.