Initiating Substance Use in Adolescence: Associations with rCBF

描述（由申请人提供）：拟议的项目将利用独特的机会，在物质使用之前或早期阶段调查青少年，以确定与开始使用相关的基于大脑的生物标志物，使用的严重程度和使用轨迹随着时间的推移，以及使用对发育中的大脑的影响。现有的横断面和纵向数据集（R01AA016274和ROIMH87493）包括基线时330名青少年（12-15岁）和两年随访时264名青少年（14-17岁）的行为测量和神经影像学数据。使用药物使用严重程度的一般指数（尝试两种或两种以上药物的报告，SU2+）对基线ASL-MRI图像进行的初步分析表明，与戒断者（n=98）相比，SU2+青少年（n=21）的静息脑区皮质边缘脑区血流量增加。提出的工作将(1)包括更合格的严重程度指标来澄清与rCBF的关系，(2)确定基线皮质边缘rCBF是否与未来两年临床随访中的物质使用有关，以及(3)慢性物质使用对发育中的大脑的影响。除了样本的独特性和丰富性外，关注静息rCBF对于研究发育中的大脑是理想的，因为在血管生成、突触发生或其他神经发育过程发生的大脑区域需要血液流动。然而，到目前为止，区域脑血流（rCBF）的定量测量仅限于成年人群。同样，药物使用的神经影像学研究也仅限于成人慢性使用者。因此，这项研究的结果将是该年龄组的首次报道，特别是因为rCBF与药物使用有关。

DESCRIPTION (provided by applicant): The proposed project will take advantage of the unique opportunity to investigate adolescents prior to or at the early stages of substance use to identify brain-based biomarkers associated with initiation of use, the severity of use and the trajectory of use over time, and the impact of use on the developing brain. The existing, cross- sectional and longitudinal data set (R01AA016274 and ROIMH87493) includes behavioral measures and neuroimaging data for 330 adolescents (age 12-15) at baseline and 264 (age 14-17) at two-year follow-up. Preliminary analyses of ASL-MRI images at baseline using a general index of substance use severity (report of trying two or more substances, SU2+) indicate that resting regional cerebral blood flow to cortico-limbic brain regions is elevated in SU2+ adolescents (n=21) relative to those who were abstinent (n=98). The work proposed will (1) include more qualified severity metrics to clarify associations with rCBF, (2) determine whether baseline cortico-limbic rCBF is associated with future substance use over the two-year clinical follow- up, and (3) the effects of chronic substance use on the developing brain. In addition to the uniqueness and richness of the sample, the focus on resting rCBF is ideal for studying the developing brain as blood flow is required in brain regions where angiogenesis, synaptogenesis or other processes of neurodevelopment are occurring. However, to date quantitative measure of regional cerebral blood flow (rCBF) has been restricted to adult populations. As well, neuroimaging studies of substance use have been limited to adult, chronic users. Therefore, the outcomes produced from this study will be the first reported in this age group, particularly as rCBF relates to substance use. PUBLIC HEALTH RELEVANCE: Nine to 15% of adolescents report using substances and 5% meet criterion for dependence making substance use and future abuse and dependence a major health problem. This work will help to clarify the effects of chronic use on the developing brain and ultimately how these effects may predict future abuse or dependence.