Prefrontal Function in Adolescent Limited vs Life Course Persistent SUD

青少年前额功能有限与终生持续 SUD

• 批准号: 7628958
• 负责人: Michael Damingo De Bellis
• 金额: $ 67.05万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-06-01 至 2013-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7628958
• 关键词: Adolescence; Adolescent; Age; Age of Onset; Alcohol consumption; Alcohol or Other Drugs use; Alcohols; American Indians; Amygdaloid structure; Area Under Curve; Attention; Brain; Cannabis; Case-Control Studies; Cells; Child; Clinical; Cognitive; Comorbidity; Consumption; Control Groups; DSM-IV; Decision Making; Dependence; Development; Diagnosis; Disease; Ethanol toxicity; Evaluation; Family history of; Female; Functional Magnetic Resonance Imaging; Functional disorder; Hippocampus (Brain); Individual; Intervention; Longitudinal Studies; MRI Scans; Marijuana Smoking; Measures; Mediating; Memory; Mental Health; Mental disorders; Morbidity - disease rate; Neurobiology; Participant; Pattern; Performance; Pharmaceutical Preparations; Population; Prefrontal Cortex; Public Health; Recording of previous events; Recruitment Activity; Resources; Rewards; Risk; Sampling; System; Uncertainty; addiction; adolescent substance abuse; base; cognitive function; comparison group; design; effective therapy; executive function; follow-up; high risk; life course persistent; neuropsychological; public health relevance; response; sex; white matter; young adult

DESCRIPTION (provided by applicant): The focus of this application is to understand the brain mechanisms of persistence versus desistence of adolescent onset alcohol and/or marijuana use disorder (defined as DSM-IV substance abuse/dependence (SUD)) from adolescence into young adulthood. We propose to measure prefrontal and hippocampal cognitive function with a comprehensive neuropsychological battery and a functional MRI (fMRI) scan paradigm, the Decision-Reward Uncertainty Task, designed to challenge the two major subdivisions of prefrontal cortex (PFC), the dorsolateral (dlPFC) and ventromedial (vmPFC) systems. DlPFC and vmPFC serve distinct components of executive functions involved in decision making and reward evaluation, respectively. SUDs are associated with dysfunction in these PFC systems. The application builds on a unique longitudinal study of a representative population sample of children: the Great Smoky Mountains Study (GSMS). Participants (N=1,411 surviving) were first assessed for Axis I disorders including drug and alcohol use, abuse, and addiction in 1993 at ages 9-13, and have received an average of 6 assessments so far. Half the participants are female, and 25% of the sample is American Indian. Participants will be recruited from the GSMS, which re-assesses DSM-IV Axis I diagnosis at ages 26-28, and on the basis of which 160 will be recruited into a case-control study (40 in each cell): 1) adolescence-limited SUD (AL- SUD), 2) adolescent persistent also called life course persistent SUD (LCP -SUD), 3) a high risk for SUD group of young adults (high risk group) with a history of adolescent psychiatric disorders who do not have a history of SUDs and are age, sex, and sociodemographically matched to the SUD subjects, and 4) a control group with no history of SUD or major Axis I disorders. Neurobiological studies of an adolescent onset SUD need to control for co-morbidity since the PFC deficits seen in mental disorders may be responsible for the increased risk for SUD. We predict that there will be dlPFC and vmPFC functional differences in subjects with LCP-SUD vs. AL-SUD. This proposal will also allow us to measure the effects of an adolescent limited vs persistent SUD on young adult prefrontal and hippocampal structural and functional development. We expect that we will observe significant differences in the patterns of dlPFC and vmPFC activity, cognitive function, and hippocampal volumes between AL-SUD, LCP SUD, high risk, and control groups. PUBLIC HEALTH RELEVANCE Understanding the neurobiological underpinnings of individuals who go on to have lifelong problems with drugs and alcohol versus those who do not has important relevance to public health. This understanding can help to better identify those at risk and to help develop better treatments and deliver resources and interventions to these vulnerable individuals. Understanding of brain dysfunction of addiction is critical for more effective treatments of adolescent substance abuse.

描述（由申请人提供）：本申请的重点是了解青少年发作的酒精和/或大麻使用障碍（定义为DSM-IV物质滥用/依赖（SUD））从青春期到青年期的持久性和持久性的大脑机制。我们建议通过综合神经心理学电池和功能MRI （fMRI）扫描范式来测量前额叶和海马的认知功能，决策-奖励不确定性任务，旨在挑战前额叶皮层（PFC）的两个主要分支，背外侧（dlPFC）和腹内侧（vmPFC）系统。DlPFC和vmPFC分别在决策和奖励评估中起着不同的执行功能。sud与这些PFC系统的功能障碍有关。该应用程序建立在一个独特的纵向研究的代表性人口样本的儿童：大烟山研究（GSMS）。1993年，9-13岁的参与者（N= 1411名存活者）首次接受了包括药物和酒精使用、滥用和成瘾在内的第一轴疾病评估，迄今为止平均接受了6次评估。一半的参与者是女性，25%的样本是美国印第安人。参与者将从GSMS中招募，GSMS将在26-28岁时重新评估DSM-IV轴I诊断，并在此基础上招募160人进入病例对照研究（每个细胞40人）：1)青少年限制性SUD （AL- SUD), 2)青少年持续性也称为生命过程持续性SUD （LCP -SUD), 3）有青少年精神障碍病史但无SUD病史且年龄、性别和社会人口学特征与SUD受试者相匹配的青年人（高风险组），以及4）无SUD病史或主要I轴障碍的对照组。由于精神障碍中出现的PFC缺陷可能是导致SUD风险增加的原因，因此青少年发病SUD的神经生物学研究需要控制合并症。我们预测LCP-SUD与AL-SUD受试者的dlPFC和vmPFC功能存在差异。这一建议也将使我们能够衡量青少年限制性和持续性SUD对年轻人前额叶和海马结构和功能发育的影响。我们期望在AL-SUD、LCP SUD、高风险组和对照组之间观察到dlPFC和vmPFC活动模式、认知功能和海马体积的显著差异。与公共卫生相关的研究了解终身受毒品和酒精困扰的个体与不受毒品和酒精困扰的个体之间的神经生物学基础，对公共卫生具有重要的相关性。这种理解可以帮助更好地识别那些有风险的人，帮助开发更好的治疗方法，并向这些脆弱的个体提供资源和干预措施。了解成瘾的脑功能障碍对于更有效地治疗青少年药物滥用至关重要。