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 继续和停止问题物质使用(SU)和反社会行为(ASB)，始于 青春期。我们建议在最初招聘约18年后，对一名 当青少年过渡到中年时，他们的样本受到极大的影响；这是一个发展时期 当我们预计这些人中的一部分会减少或停止有问题的SU和相关的高风险时 行为，而其他人会坚持最严重、最具破坏性的行为，导致毁灭性的高 发病率和死亡率。这项建议的目的是： 目标1：确定预测青春期SU和ASB水平和变化(增长或下降)的危险因素 到中年。 A.我们假设发病早期、男性、虐待儿童、神经认知缺陷和 个性特征(行为失控/冲动)将预示更高水平和更多的SU成长 和ASB。 B.我们假设，以多基因风险分数(PR)为指标的遗传易感性将更快地预测 SU和ASB的生长一直持续到成年后期。 C.我们将探索机械关系；例如，我们假设PR和 SU和ASB的水平和变化将部分地由行为控制不足/冲动所介导。 目的2：确定与SU和ASB水平及变化相关的保护因素。 A.我们假设，采用成人亲社会角色(教育、就业、婚姻、育儿)将 与SU和ASB生长减慢有关。 B.我们假设，治疗将与SU和ASB的停药有关，而不是 监禁。 C.我们将探索遗传脆弱性的调节因素，特别是亲社会角色和治疗 减弱云芝多糖对SU和ASB水平的影响。 目标3：确定结果在多大程度上特定于我们精心挑选的样本中患有 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推广 我们的高危样本和类似的纵向数据来自我们目前资助的双胞胎研究，一个未被选中的 基于社区的样本。 A.我们假设风险和保护因素在两个样本中的作用相似，尽管 在高风险样本中，我们将有更大程度的风险因素。 B.我们将在对高危和社区双胞胎样本的联合分析中证实这一假设。