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

项目摘要摘要 受AUD影响的家庭承受的经济、身体和精神伤害是巨大的。750万美国儿童 与患有AUD的父母生活在一起，除了高度重视外，还增加了贫困、虐待和忽视的风险 酒精问题的遗传风险。AUDS的缓解是很常见的，但在 对AUDS的成本和后果进行研究。高达50%的人有终生AUDS经历 病情缓解，许多是在澳门氏症发作后14年内，许多是在生育和养育子女的最佳时期。我们的 该项目的总体目标是全面探讨缓解表型及其在急性白血病中的作用。 AUDS的代际传播。我们将使用来自合作研究的基于家庭的数据 酒精中毒的遗传学，这项研究自1989年以来一直在进行，招募有AUDS高危家庭和 超过15,000名酗酒者。由于COGA的高风险设计，有足够数量的AUD- 受影响的个人(N=7724，49%)，因此可以获得缓解，以允许进行这种缓解检查 家庭内部及其对后代结局的影响。在目标1中，我们将使用生存分析和以人为中心 描述AUD和缓解(慢性AUD，稳定或复发)病程的纵向方法 缓解，通过不同类型的缓解[禁欲和非禁欲]的行动)并确定人口统计学 缓解和复发的行为前兆和后遗症(婚姻状况、子女、就业、 收入、教育、共生物质和精神障碍、治疗)。在探索性分析中，我们将 构建缓解期家庭密度的测量方法，并测试其与AUD和缓解期的关系。因为 影响AUD和缓解的遗传和环境因素并不完全重叠，我们预计这一点 测量与不发生AUD的概率以及与 AUD患者缓解的可能性与AUD的多基因风险(PR)无关。在目标2中，我们使用 青春期子女(家庭)家庭环境特征的亲子配对研究 收入、父母婚姻状况、童年创伤)以及青少年和成年子女饮酒情况的差异 以及作为父母AUD/缓解的函数的AUD/缓解。兄弟姐妹的比较将为谁描绘出来 父母的减免可能会产生最大的影响，同时对潜在的遗传和 兄弟姐妹共有的环境混杂因素。该提案的创新之处在于其对韧性的关注，而不是 风险，在个人和家庭中；将父母AUD/减免的影响扩大到青年和中年人 成年期；以及它使用遗传知情的方法来理解缓解在 AUDS的代际传播。结果可以为临床医生提供杠杆，以鼓励在 已经或计划成为父母并将为改善预防和治疗工作做出贡献的患者 减少AUD及相关问题的代际传播。

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.