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，调查青少年之前或在物质使用的早期阶段，以确定与开始使用相关的基于大脑的生物标志物，使用的严重程度和随着时间的推移使用的轨迹，以及使用对大脑发育的影响。现有的横断面和纵向数据集（R 01 AA 016274和ROIMH 87493）包括基线时330名青少年（12-15岁）和2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。使用物质使用严重程度的一般指数（尝试两种或多种物质的报告，SU 2+）对基线时的ASL-MRI图像进行初步分析，结果表明，相对于禁欲者（n=98），SU 2+青少年（n=21）中皮质边缘脑区的静息局部脑血流量升高。拟议的工作将（1）包括更合格的严重性指标，以澄清与rCBF的关联，（2）确定基线皮质边缘rCBF是否与未来两年临床随访期间的物质使用相关，以及（3）长期物质使用对发育中大脑的影响。除了样本的独特性和丰富性之外，对静息rCBF的关注对于研究发育中的大脑是理想的，因为在发生血管生成、突触发生或其他神经发育过程的大脑区域中需要血流。然而，到目前为止，定量测量局部脑血流量（rCBF）已被限制到成人人群。同样，对物质使用的神经影像学研究也仅限于成年人，长期使用者。因此，这项研究产生的结果将是该年龄组的首次报告，特别是因为rCBF与药物使用有关。 公共卫生相关性：9%至15%的青少年报告使用药物，5%达到依赖标准，使药物使用和未来滥用和依赖成为主要的健康问题。这项工作将有助于澄清长期使用对发育中的大脑的影响，以及这些影响最终如何预测未来的滥用或依赖。

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.