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.

项目摘要摘要 由校园影响的家庭承担的经济，身体和情感危害很棒。 750万美国儿童 与受声音影响的父母一起生活，除了加剧外，还增加了贫困，虐待和忽视的风险 酒精问题的遗传风险。从AUDS中缓解很常见，但这很少在 研究音频的成本和后果。最多有50％的人有终身音频经验 缓解，许多人在发作后的14年内，许多在育儿和育儿的年度中。我们的 该项目的广泛目标是全面探究缓解表型及其在 澳元的代际传输。我们将使用有关协作研究的基于家庭的数据 酗酒的遗传学，这是一项自1989年以来一直在进行的研究，该研究招募了具有高度风险和的家庭 超过15,000多个饮酒者。由于COGA的高风险设计，有足够数量的声音 受影响的个体（n = 7724，49％），因此可缓解，以允许此缓解检查 家庭内部及其对后代结果的影响。在AIM 1中，我们将使用生存分析和以人为中心 纵向方法来表征AUD和缓解的过程（慢性AUD，稳定或复发 缓解，通过不同类型的缓解运动[戒酒，非属性]）并确定人口统计 以及缓解和复发的行为先例和序列（婚姻状况，儿童，就业， 收入，教育，同时发生的物质和精神疾病，治疗）。在探索性分析中，我们将 构建一种衡量家庭密度的量度，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能完全重叠，我们期望这一点 与不发展AUD的可能性相关的措施，与 AUD的个体，与AUD的多基因风险（PR）无关。在AIM 2中，我们使用 生物父母的春季围绕青少年后代的家族环境（家庭）的家族环境 收入，父母的婚姻状况，童年创伤）以及青少年和成人后代的差异 和AUD/缓解是父母AUD/缓解的函数。兄弟姐妹比较将为谁描述 父母的缓解可能会产生最大的影响，同时为潜在的遗传和 兄弟姐妹共享的环境混杂因素。该提议的重点是弹性，而不是 风险，个人和家庭；在扩展父母aud/缓解年轻和中期的影响时 成年并使用一种遗传信息的方法来理解缓解在 澳元的代际传输。结果可以为临床医生提供杠杆作用，以鼓励康复 正在或计划成为父母的患者，并将为改进的预防和治疗工作做出贡献 减少auds和相关问题的代际传输。