Adult Progression of Adolescent Onset Substance Use Disorder in a High Risk Sample

高风险样本中青少年发作药物使用障碍的成人进展

• 批准号: 10677547
• 负责人: Christian J Hopfer
• 金额: $ 65.18万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-15 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10677547
• 关键词: Address; Adolescence; Adolescent; Adopted; Adult; Affect; Age; Age Years; Age of Onset; Alcohol consumption; Alcohols; American; Amphetamines; Architecture; Attenuated; Behavior; Behavioral; California; Cessation of life; Child Abuse and Neglect; Child Rearing; Cocaine; Cocaine Dependence; Cognitive; Colorado; Communities; Complex; Conduct Disorder; Data; Data Analyses; Data Collection; Development; Disease; Education; Employment; European; Exhibits; Female; Funding; Genetic; Genetic Predisposition to Disease; Genotype; Growth; Imprisonment; Impulsivity; Individual; Joints; Longitudinal Studies; Marijuana; Marriage; Measures; Mediating; Mental Health; Methamphetamine dependence; Morbidity - disease rate; Neurocognitive Deficit; Opiate Addiction; Opioid; Participant; Personality Character; Personality Traits; Pharmaceutical Preparations; Predictive Factor; Problem behavior; Reporting; Request for Proposals; Research; Risk Behaviors; Risk Factors; Role; Sampling; Severities; Substance Use Disorder; Symptoms; Teenagers; Tobacco; Twin Multiple Birth; Twin Studies; Youth; addiction; antisocial behavior; comorbidity; comparative; early onset substance use; follow up assessment; follow-up; high risk; high risk behavior; high-risk adolescents; indexing; injection drug use; male; marijuana use; mortality; nicotine use; polygenic risk score; protective factors; psychiatric comorbidity; psychosocial; recruit; sex; substance use; substance user; young adult

The research proposed in this application aims to understand risk and protective factors that promote continuation and desistance of problematic substance use (SU) and antisocial behavior (ASB) that began in adolescence. We propose a fourth wave of follow-up, approximately 18 years after initial recruitment, of an extremely affected adolescent sample as they transition into middle adulthood; this is a developmental period when we expect a portion of these individuals to decrease or desist problematic SU and associated high-risk behaviors, while others will persist with the most serious, destructive behaviors leading to devastatingly high rates of morbidity and mortality. The aims of this proposal are to: Aim 1: Identify risk factors that predict level and change (growth or decline) in SU and ASB from adolescence to middle adulthood. a. We hypothesize that early age of onset, male sex, child maltreatment, neurocognitive deficits, and personality traits (behavioral undercontrol/impulsivity) will predict higher levels and more growth in SU and ASB. b. We hypothesize that genetic vulnerability as indexed by polygenic risks scores (PRS) will predict faster growth in SU and ASB that persists through later adulthood. c. We will explore mechanistic relationships; e.g., we hypothesize that the relationship between PRS and level and change of SU and ASB will be partially mediated by behavioral undercontrol/impulsivity. Aim 2: Identify protective factors associated with level and change in SU and ASB. a. We hypothesize that adopting adult prosocial roles (education, employment, marriage, parenting) will be associated with lessened growth in SU and ASB. b. We hypothesize that treatment will be associated with greater desistance of SU and ASB than incarceration. c. We will explore moderators of genetic vulnerability, specifically whether prosocial roles and treatment attenuate the effect of PRS on level of SU and ASB. Aim 3: Determine the extent to which findings are specific to our highly selected sample of individuals with early-onset SU and ASB or generalize more broadly by conducting comparative and joint analyses of data from our high-risk sample with similar longitudinal data from our currently funded study of twins, an unselected community-based sample. a. We hypothesize that risk and protective factors will operate similarly across the two samples, although we will have a greater magnitude of risk factors in the high-risk sample. b. We will confirm this hypothesis in joint analyses of the high-risk and community twin samples.

本申请中提出的研究旨在了解促进的风险和保护因素 持续和停止有问题的物质使用（SU）和反社会行为（ASB） 青春期。我们建议在初次招募后约 18 年进行第四波后续行动， 青少年样本在过渡到中年时受到极大影响；这是一个发展时期 当我们期望其中一部分人减少或停止有问题的 SU 和相关的高风险时 行为，而其他人则坚持最严重的、破坏性的行为，导致毁灭性的高 发病率和死亡率。该提案的目的是： 目标 1：确定预测青春期后 SU 和 ASB 水平和变化（增长或下降）的风险因素 到中年。 一个。我们假设发病年龄早、男性、虐待儿童、神经认知缺陷和 人格特质（行为失控/冲动）将预测 SU 的更高水平和更多增长 和ASB。 b.我们假设以多基因风险评分（PRS）为索引的遗传脆弱性将更快地预测 SU 和 ASB 的生长持续到成年后期。 c.我们将探索机械关系；例如，我们假设 PRS 和 SU 和 ASB 的水平和变化将部分受到行为控制不足/冲动的调节。 目标 2：确定与 SU 和 ASB 水平和变化相关的保护因素。 一个。我们假设，采用成人亲社会角色（教育、就业、婚姻、养育子女）将 与 SU 和 ASB 生长减缓有关。 b.我们假设与治疗相比，治疗对 SU 和 ASB 的抑制作用更大 监禁。 c.我们将探讨遗传脆弱性的调节因素，特别是亲社会角色和治疗是否 减弱 PRS 对 SU 和 ASB 水平的影响。 目标 3：确定研究结果对于我们精心挑选的个体样本的特定程度 早发性 SU 和 ASB 或通过对以下数据进行比较和联合分析进行更广泛的概括： 我们的高风险样本具有来自我们目前资助的双胞胎研究的类似纵向数据，这是一项未经选择的研究 基于社区的样本。 一个。我们假设风险和保护因素在两个样本中的作用相似，尽管 我们将在高风险样本中拥有更大量的风险因素。 b.我们将在高风险和社区双胞胎样本的联合分析中证实这一假设。