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病的酒精和/或大麻使用障碍（定义为 DSM-IV 药物滥用/依赖 (SUD)）从青春期到成年早期的持续与停止的大脑机制。我们建议通过综合神经心理学电池和功能性 MRI (fMRI) 扫描范例（决策奖励不确定性任务）来测量前额叶和海马认知功能，旨在挑战前额叶皮层 (PFC) 的两个主要分区，即背外侧 (dlPFC) 和腹内侧 (vmPFC) 系统。 DlPFC 和 vmPFC 分别服务于涉及决策和奖励评估的执行功能的不同组成部分。 SUD 与这些 PFC 系统的功能障碍有关。该应用程序建立在对儿童代表性人口样本的独特纵向研究：大烟山研究 (GSMS) 的基础上。 1993 年，9 至 13 岁的参与者（N = 1,411 名幸存者）首次接受了 Axis I 疾病评估，包括吸毒和酗酒、滥用和成瘾，迄今为止平均接受了 6 次评估。一半的参与者是女性，25% 的样本是美洲印第安人。将从 GSMS 中招募参与者，该系统重新评估 26-28 岁的 DSM-IV Axis I 诊断，并在此基础上招募 160 名参与者进行病例对照研究（每个单元 40 名）：1) 青春期限制性 SUD (AL-SUD)，2) 青少年持续性也称为生命历程持续性 SUD (LCP-SUD)，3) 青少年 SUD 高风险组（高 风险组）有青少年精神疾病史，没有 SUD 病史，并且年龄、性别和社会人口统计学与 SUD 受试者相匹配，4）没有 SUD 或主要轴 I 疾病史的对照组。对青少年 SUD 的神经生物学研究需要控制共病，因为精神障碍中的 PFC 缺陷可能是 SUD 风险增加的原因。我们预测 LCP-SUD 与 AL-SUD 受试者的 dlPFC 和 vmPFC 功能存在差异。该提案还将使我们能够衡量青少年有限的 SUD 与持续的 SUD 对年轻人前额叶和海马结构和功能发育的影响。我们预计我们将观察到 AL-SUD、LCP SUD、高风险组和对照组之间 dlPFC 和 vmPFC 活动模式、认知功能和海马体积的显着差异。公共健康相关性 了解终生因毒品和酒精问题而终生困扰的个体与没有这些问题的个体的神经生物学基础，对于公共健康具有重要意义。这种理解有助于更好地识别面临风险的人，并帮助开发更好的治疗方法并向这些弱势群体提供资源和干预措施。了解成瘾引起的大脑功能障碍对于更有效地治疗青少年药物滥用至关重要。