HIGH FIELD MRI OF STIMULANTS IN ADOLESCENTS AT RISK

描述(由申请人提供)：本申请是对(PAR-02-058)影像科学轨道研究过渡奖(I/START)的响应，该奖项旨在研究可能导致物质使用障碍(SUD)的神经行为和神经生物学因素。第一个目标是在4T时获得刺激反应中个体功能差异的初步fMRI测量，以及SUD风险男性青少年中多动和结构MRI的客观行为测量，从而复制1.5T下发表的结果。第二个目标是在NIDA赞助的导师研究科学家发展奖的赞助下，为针对患有品行障碍(CD)的男性和女性青少年的应用开发初步数据。 行为多动(BH)和冲动的品行障碍是SUD的已知先兆，特别是有SUD阳性家族史的患者。行为多动及其个体差异经常被认为是CD和进展为SUD之间的关键联系。我们使用光学跟踪运动测量了BH的个体差异，并报告了相关的基底节和小脑多巴胺转运体(DAT)丰富亚区的血流异常，这些亚区被哌酸甲酯(MPH)剂量依赖地减少。过度活跃和刺激反应率似乎反映了基底神经节-小脑系统中DAT丰富的亚区之间不成比例的血流。我们假设，基底节-小脑系统中的这些功能和/或结构缺陷将BH与SUD的风险联系起来。 为了测试关于BH、对MPH的反应性和DAT富集区的体积的功能和结构假说，我们将使用4T相控阵MRI检查四组青少年男性(14-17岁)(每组n=10)。两个患有(DSM-IV+)ADHD和与SUD(SUD+)有一级亲属关系的对立违抗性障碍ODD的队列，将在扫描MPH前和后扫描之前用光学跟踪仔细筛查是否存在(BH+/SUD+)或不存在多动(BH-/SUD+)，并与匹配的(DSM-IV-)对照组、有(BH-/SUD+)和没有(BH-/SUD-)SUD家族史的组进行比较。 因此，对患有ADHD/ODD的BH+/BH-个体进行成像将使人们能够前瞻性地关注SUD高危人群中的先天神经行为和神经生物学因素，而不会受到发达的CD或既往药物滥用对大脑发育的混淆。

DESCRIPTION (provided by applicant): This application is in response to (PAR-02-058) Imaging - Science Track Award for Research Transition (I/START) for the study of neurobehavioral and neurobiological factors that may contribute to the initiation of substance use disorders (SUD). The first objective is to obtain preliminary fMRI measurements at 4T of individual functional differences in stimulant response coupled with objective behavioral measures of hyperactivity and structural MRI in a subgroup of male adolescents at risk for SUD, thus, replicating published findings at 1.5 T. The second is to develop preliminary data for an application targeting both male and female adolescents with conduct disorder (CD) under the auspices of a NIDA sponsored Mentored Research Scientist Development Award. Conduct disorder with behavioral hyperactivity (BH) and impulsivity is a known precursor to SUD, particularly with a positive family history of SUD. Behavioral hyperactivity, and its individual variation, is often cited as a critical link between CD and progression to SUD. We have measured, using optical tracking of movement, individual variations in BH, and have reported correlated blood flow abnormalities in dopamine transporter (DAT) rich subregions of the basal ganglia and cerebellum that were reduced, dose-dependently, by methylphenidate (MPH). Hyperactivity and stimulant response-rate appear to mirror disproportionate blood flow among DAT-rich subregions of the basal ganglia-cerebellar system. We hypothesize, those functional and/or structural defects in the basal ganglia-cerebellar system link BH with risk for SUD. To test functional and structural hypotheses about BH, responsiveness to MPH and volumes of DAT-rich subregions, we will examine, using phased-array MRI at 4T, four groups (n=10 each) of adolescent males (14-17 yrs). Two cohorts with (DSM-IV+) ADHD and comorbid oppositional defiant disorder ODD, having a first degree relative with SUD (SUD+), will be carefully screened with optical tracking for either presence (BH+/ SUD+) or absence of hyperactivity (BH-/SUD+) prior to scanning pro- and post-MPH, and compared with matched, (DSM-IV-) comparison groups, with (BH-/SUD+) and without (BH-/SUD-) a family history of SUD. Thus, imaging BH+/BH- individuals with ADHD/ODD will allow a prospective focus on antecedent neurobehavioral and neurobiological factors, in a population at high risk for SUD, without the confounds of developed CD or prior substance abuse on brain development.