Genetics and Progression of Early-onset Substance Dependence and HIV Risk

早发性物质依赖和艾滋病毒风险的遗传学和进展

• 批准号: 8693248
• 负责人: Christian J Hopfer
• 金额: $ 101.49万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-15 至 2019-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8693248
• 关键词: 14 year old; 18 year old; AIDS/HIV problem; ARHGEF5 gene; Address; Adolescence; Adolescent; Adult; Affect; Alcohol abuse; Alcohol or Other Drugs use; Amphetamines; Architecture; Behavior; Behavioral; Biological; Cessation of life; Characteristics; Cocaine; Cocaine Dependence; Cognition; Collaborations; Communities; Comorbidity; Complex; Conduct Disorder; Consultations; Criminal Justice; DNA; Data; Data Collection; Dependence; Development; Disease; Disinhibition; Dizygotic Twins; Drug Addiction; Enrollment; Environment; Environmental Risk Factor; Event; Exhibits; Family; Genetic; Genotype; Goals; HIV risk; Housing; Imprisonment; Individual; Joints; Life; Link; Longitudinal Studies; Marijuana; Measures; Methamphetamine dependence; Monozygotic Twinning; Monozygotic twins; Morbidity - disease rate; National Institute of Drug Abuse; Neurocognitive; Nicotine; Occupational; Opiate Addiction; Opiates; Parents; Participant; Pharmaceutical Preparations; Problem behavior; Public Health; Recruitment Activity; Reporting; Research; Resources; Risk Behaviors; Risk Factors; Role; Sampling; Severities; Sexual Partners; Siblings; Social Environment; Social support; Staging; Substance Addiction; Substance Use Disorder; Symptoms; Testing; Time; Twin Multiple Birth; Unsafe Sex; Work; Youth; addiction; anti social; base; comparative; critical developmental period; design; early onset; early onset substance use; family genetics; follow-up; genetic analysis; genetic epidemiology; high risk; high risk behavior; high risk sexual behavior; injection drug use; mortality; proband; psychosocial; public health relevance; self help; sex; substance abuse treatment; underage drinking; young adult; 14 year old; 18 year old; AIDS/HIV problem; ARHGEF5 gene; Address; Adolescence; Adolescent; Adult; Affect; Alcohol abuse; Alcohol or Other Drugs use; Amphetamines; Architecture; Behavior; Behavioral; Biological; Cessation of life; Characteristics; Cocaine; Cocaine Dependence; Cognition; Collaborations; Communities; Comorbidity; Complex; Conduct Disorder; Consultations; Criminal Justice; DNA; Data; Data Collection; Dependence; Development; Disease; Disinhibition; Dizygotic Twins; Drug Addiction; Enrollment; Environment; Environmental Risk Factor; Event; Exhibits; Family; Genetic; Genotype; Goals; HIV risk; Housing; Imprisonment; Individual; Joints; Life; Link; Longitudinal Studies; Marijuana; Measures; Methamphetamine dependence; Monozygotic Twinning; Monozygotic twins; Morbidity - disease rate; National Institute of Drug Abuse; Neurocognitive; Nicotine; Occupational; Opiate Addiction; Opiates; Parents; Participant; Pharmaceutical Preparations; Problem behavior; Public Health; Recruitment Activity; Reporting; Research; Resources; Risk Behaviors; Risk Factors; Role; Sampling; Severities; Sexual Partners; Siblings; Social Environment; Social support; Staging; Substance Addiction; Substance Use Disorder; Symptoms; Testing; Time; Twin Multiple Birth; Unsafe Sex; Work; Youth; addiction; anti social; base; comparative; critical developmental period; design; early onset; early onset substance use; family genetics; follow-up; genetic analysis; genetic epidemiology; high risk; high risk behavior; high risk sexual behavior; injection drug use; mortality; proband; psychosocial; public health relevance; self help; sex; substance abuse treatment; underage drinking; young adult

DESCRIPTION (provided by applicant): The research proposed in this application aims to understand genetic and environmental factors that promote desistance or continuation of problematic substance use and associated high-risk behaviors that began in adolescence. We propose an ~12-year follow-up (6 years after an initial 6-year follow-up) of an extremely affected adolescent sample as they transition into adulthood; this is a critical developmental period when we expect a portion of these individuals to decrease or desist problematic substance use and associated high-risk behaviors, while others will persist with the most serious, destructive behaviors leading to devastatingly high rates of morbidity and mortality. Our central goal is to understand the genetic and environmental factors that delineate these life trajectories. Results from our longitudinal research demonstrate that adolescent-onset substance users, who primarily exhibited abuse of and dependence on marijuana, nicotine, and alcohol during adolescence, progressed in the severity of their substance use five years later. As young adults, they report dramatically high rates of lifetime cocaine (29.2%), amphetamine (29.2%), and opiate (10.8%) use disorders as well as HIV/AIDS-related risk behaviors such as injection drug use (11%) and risky sexual behaviors. Indeed, when compared with community samples, these individuals report more than twice the number of lifetime sexual partners and a 33% higher rate of unprotected sex. Furthermore, they exhibit alarming rates of adult incarceration (55%) and early death (2.6%). This proposal extends our multiple-PI collaboration focused on the genetic epidemiology of adolescent-onset drug dependence. The three specific aims are to: 1) Identify distinct developmental trajectories of substance use, antisocial, and HIV risk behaviors in probands and siblings from adolescence to adulthood. a) Test initial characteristics of the adolescents, such as sex, severity of early onset substance use disorders (SUDs) and conduct disorder (CD), and neurocognitive functioning (e.g., disinhibition) that predict these trajectories and b) Test whether adult resources such as treatment for SUDs, housing stability, occupational stability, and social support are associated with these trajectories. 2) Determine the genetic and environmental architecture of developmental trajectories of substance use disorders, antisocial and HIV risk behaviors. a) Test the moderating role of social context, such as SES, criminal justice involvement, substance abuse treatment/self-help involvement, and stressful life events, in altering genetic influence and b) Test whether moderating effects vary across developmental periods (adolescence, young adulthood, and adulthood). 3) Test the influence of shared versus specific etiologic influences on measures of SUDs, antisocial behaviors, and HIV risk behaviors across development.

描述（由申请人提供）：本申请中提出的研究旨在了解促进有问题的物质使用和相关的高风险行为的遗传和环境因素。我们提出了一个受影响的青少年样本过渡到成年后的受影响极大的青少年样本的约12年的随访（最初6年后的6年随访）；这是一个关键的发展时期，当我们期望这些人中的一部分会减少或消除有问题的物质使用以及相关的高风险行为，而其他人则将坚持使用最严重，最破坏性的行为，从而导致发病率和死亡率较高。我们的核心目标是了解描述这些生命轨迹的遗传和环境因素。我们的纵向研究的结果表明，青少年发作的药物使用者主要在青春期表现出滥用和对大麻，尼古丁和酒精的依赖，在五年后的严重性中进展。作为年轻人，他们报告的终生可卡因（29.2％），苯丙胺（29.2％）和阿片类（10.8％）使用障碍以及与HIV/AIDS相关的风险行为（例如注射药物使用（11％）和风险性行为）的率很高。的确，与社区样本相比，这些人报告了终身性伴侣的数量两倍多，未受保护的性别率提高了33％。此外，它们表现出令人震惊的成人监禁率（55％）和早期死亡（2.6％）。该建议扩展了我们的多重合作，重点是青少年发作的药物依赖性的遗传流行病学。这三个具体目的是：1）从青春期到成年期的概率和兄弟姐妹中的物质使用，反社会和艾滋病毒风险行为的不同发展轨迹。 a）青少年的测试初始特征，例如性别，早期发作药物使用障碍（SUD）和行为障碍（CD）的严重程度以及预测这些轨迹的神经认知功能（例如，抑制） b）测试这些轨迹等成人资源（例如用于SUD，住房稳定，职业稳定性和社会支持）等成人资源是否与这些轨迹有关。 2）确定物质使用障碍，反社会和艾滋病毒风险行为的发育轨迹的遗传和环境结构。 a）测试社会背景的调节作用，例如SES，刑事司法参与，药物滥用治疗/自助介绍以及压力性的生活事件，在改变遗传影响和b）测试调节效应在整个发育时期（青少年，年轻，成年和成年）是否有所不同。 3）测试共享与特定病因的影响对跨发育的量度，反社会行为和艾滋病毒风险行为的措施的影响。