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

缓解在酒精使用障碍代际传播中的作用：病程、背景和后代结果

• 批准号: 10736096
• 负责人: VIVIA V MCCUTCHEON
• 金额: $ 36.35万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-16 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10736096
• 关键词: Adult; Adult Children; Affect; Age; Alcohol Phenotype; Alcohol abuse; Alcohol consumption; Alcohols; Behavioral; Biological; Birth; Black race; Child; Child Abuse; Child Rearing; Clinical; Data; Disease; Disease remission; Divorce; Economic Burden; Economics; Education; Emotional; Employment; Environment; Environmental Exposure; Environmental Risk Factor; Family; Fathers; General Population; Generations; Genes; Genetic; Genetic Risk; Genotype; Goals; Health Services Accessibility; Home environment; Household; Income; Individual; Inherited; Literature; Marital Status; Marriage; Measures; Mental Depression; Mental disorders; Methods; Molecular Genetics; Mothers; Movement; Nuclear Family; Onset of illness; Outcome; Parents; Participant; Patients; Phenotype; Poverty; Prevention; Probability; Recovery; Relapse; Research; Risk; Role; Running; Sampling; Science; Siblings; Societies; Substance Use Disorder; Survival Analysis; Symptoms; Testing; Variant; Woman; abuse neglect; adolescent offspring; age difference; alcohol consequences; alcohol risk; alcohol use disorder; behavioral phenotyping; child bearing; chronic alcohol ingestion; cognitive function; cohort; cost; density; design; experience; externalizing behavior; genetics of alcoholism; genome wide association study; high risk; improved; innovation; intergenerational; men; offspring; parental influence; pediatric trauma; person centered; protective effect; recruit; resilience; segregation; sex; symptomatology; transmission process; traumatic event; underage drinking; young adult

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.

项目概要摘要 受澳元影响的家庭所承受的经济、身体和情感伤害是巨大的。 750 万美国儿童 与受澳元影响的父母住在一起，除了增加贫困、虐待和忽视的风险外， 酒精问题的遗传风险。澳元的减免很常见，但这在澳大利亚很少得到承认 研究澳元的成本和后果。高达 50% 的人拥有终生澳元经历 缓解，许多在 AUD 发病后 14 年内缓解，许多在生育和抚养孩子的黄金时期缓解。我们的 该项目的总体目标是全面探讨缓解表型及其在 澳元的代际传递。我们将使用来自合作研究的基于家庭的数据 酗酒遗传学，一项自 1989 年以来持续进行的研究，招募了 AUD 和酒精中毒风险较高的家庭 超过 15,000 名曾经饮酒者。由于COGA的高风险设计，有足够数量的AUD- 受影响的个体（N = 7724，49％），因此可以缓解，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本 纵向方法来描述 AUD 和缓解过程（慢性 AUD、稳定或复发） 缓解、通过不同类型的缓解[戒断、非戒断]）并确定人口统计 缓解和复发的行为前因和后遗症（婚姻状况、子女、就业、 收入、教育、共存物质和精神疾病、治疗）。在探索性分析中，我们将 构建缓解家庭密度的衡量标准并测试其与 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，我们预计这一点 衡量与不发展 AUD 的概率以及与 AUD 患者缓解的可能性，与 AUD 的多基因风险 (PRS) 无关。在目标 2 中，我们使用 生物学亲子对来表征青少年后代的家庭环境（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的变化 以及 AUD/缓解作为父母 AUD/缓解的函数。兄弟姐妹的比较将描绘出谁的 父母的缓解可能会产生最大的影响，同时对潜在的遗传和疾病提供严格的控制。 兄弟姐妹分享的环境混杂因素。该提案的创新之处在于它关注的是复原力，而不是 个人和家庭的风险；将父母 AUD/缓解的影响扩展到年轻人和中年人 成年期；并使用遗传信息方法来理解缓解在疾病中的作用 澳元的代际传递。结果可以为临床医生提供促进康复的杠杆作用 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 减少澳元的代际传递和相关问题。