Frontal function in Adolescent Cannabis Use Disorders

描述（由申请人提供）： 为了响应RFA-DA-05-007，我们提出了一项为期5年的横断面调查，并进行了为期1年的前瞻性随访，以进一步了解青少年发作大麻使用障碍（CUD;定义为DSM-IV大麻依赖或滥用）对青少年前额和海马结构和功能发育的神经生物学后果。我们建议用一个全面的神经心理电池和功能性MRI（fMRI）扫描来测量前额叶和海马的认知功能，目的是测量参与决策和奖励的前额叶皮层（RFC）的分区。我们推测青少年CUD与前额叶和海马功能缺陷有关。将比较三个青少年组：1）患有CUD的青少年，其没有其他共病的物质使用障碍（SUD）并且正在接受强化物质治疗，2）患有精神障碍的青少年的SUD高风险组，其没有任何SUD并且在年龄、性别和社会人口统计学上与CUD受试者匹配，以及3）年龄、性别、和社会人口学匹配的健康社区对照青少年。具体目的是比较基线时青少年CUD的前额和海马结构和功能的测量值，以及基线时和6个月和12个月随访时的前额和海马神经心理功能。在基线，一个良好的特征子样本将经历一个新的功能磁共振成像任务，以测量RFC活动。我们将探讨所有青少年组RFC活动基线测量值之间的关系，以检查与以下因素相关的因素：1）青少年CUD组未缓解或进展为其他SUD; 2）高危组和健康对照组在6个月和12个月时出现青少年发作CUD。我们将探索受试者大麻使用缓解的临床汇总变量指标（缓解开始的年龄，缓解持续时间）和精神健康共病的存在，以尝试确定6个月和12个月时神经心理功能（例如改善）的最佳临床预测因子。青少年的大脑比成年人的大脑更容易受到药物滥用的影响。这项建议具有公共卫生意义，因为我们将全面评估大麻对青少年大脑和认知发展的影响，这是一个未充分研究的领域。

DESCRIPTION (provided by applicant): In response to RFA-DA-05-007, we propose a 5-year cross sectional investigation with a one-year prospective follow-up to further our understanding of the neurobiological consequences of an adolescent onset cannabis use disorders (CUD; defined as DSM-IV cannabis dependence or abuse) on adolescent prefrontal and hippocampal structural and functional development. We propose to measure prefrontal and hippocampal cognitive function with a comprehensive neuropsychological battery and a functional MRI (fMRI) scan aimed at measuring subdivisions of prefrontal cortex (RFC) involved in decision-making and reward. We hypothesize that adolescent CUD will be associated with deficits of prefrontal and hippocampal function. Three adolescent groups will be compared: 1) adolescents with CUD, who do not have other comorbid substance use disorders (SUDs) and who are entering intensive substance treatment, 2) a high risk for SUD group of adolescents with mental disorders who do not have any SUDs and are age, sex, and sociodemographically matched to the CUD subjects, and 3) age, sex, and sociodemographically matched healthy community control adolescents. Specific aims are to compare measures of prefrontal and hippocampal structure and function in adolescents with CUD at baseline and prefrontal and hippocampal neuropsychological function at baseline, and 6 and 12 month follow-ups. At baseline, a well characterized subsample will undergo a novel fMRI task to measure RFC activity. We will explore the relationship between baseline measures of RFC activity in all adolescent groups to examine factors associated with: 1) nonremission or progression to other SUDs in the adolescent CUD group; and 2) emergence of an adolescent onset CUD in the high risk and healthy control groups; at 6 and 12 months. We will explore clinical summary variable measures of the subject's remission of cannabis use (age of onset of remission, duration of remission) and presence of mental health co-morbidity to try to identify the best clinical predictors of neuropsychological function (e.g. improvement) at 6 and 12 months. The adolescent brain is more vulnerable to the effects of drug abuse than the adult brain. This proposal has public health significance because we will comprehensively evaluate the effects of marijuana on adolescent brain and cognitive development, an understudied area.