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饮酒和/或大麻使用障碍（定义为青少年至年轻人的DSM-IV药物滥用/依赖（SUD））的大脑机制与青少年饮酒和/或大麻使用障碍（定义为DSM-IV药物滥用/依赖（SUD））的大脑机制。我们建议通过全面的神经心理学电池和功能性MRI（FMRI）扫描范式来测量前额叶和海马认知功能，这是决策回报的不确定性任务，旨在挑战前额叶皮层（PFC）的两个主要子段，即背侧（DLPFC）和VENTROMEDIAL（VMPFC）（VMPFC）。 DLPFC和VMPFC分别提供决策和奖励评估涉及的执行职能的不同组成部分。 SUD与这些PFC系统中的功能障碍有关。该申请基于对儿童代表人群样本的独特纵向研究：大烟山研究（GSM）。首先对参与者（n = 1,411个幸存）进行了评估，以评估1993年9至13岁的1993年毒品和酒精使用，滥用和成瘾的轴I疾病，到目前为止平均接受了6次评估。参与者的一半是女性，样本的25％是美洲印第安人。 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风险群体）具有青春期精神疾病史，没有SUD史，年龄，性行为和社会数学与SUD学科相匹配，以及4）一个没有SUD或主要I障碍史的对照组。青少年发作SUD的神经生物学研究需要控制合并症，因为精神疾病中看到的PFC缺陷可能是导致SUD风险增加的原因。我们预测，LCP-SUD与Al-SUD的受试者中将存在DLPFC和VMPFC功能差异。该提案还将使我们能够衡量青少年有限与持续的SUD对年轻成人前额叶和海马结构和功能发展的影响。我们预计我们将观察到DLPFC和VMPFC活性，认知功能以及Al-SUD，LCP SUD，高风险和对照组之间的海马体积的模式存在显着差异。公共卫生的相关性理解了继续在毒品和酒精中终生问题的人的神经生物学基础，而与与公共卫生无关的人的神经生物学基础。这种理解可以帮助更好地识别有风险的人，并帮助开发更好的治疗方法，并为这些脆弱的人提供资源和干预措施。了解成瘾的大脑功能障碍对于更有效的青少年滥用药物的治疗至关重要。