Longitudinal fMRI Study of Youth at Risk for Drug Abuse

描述（由申请人提供）： 该指导研究科学家发展奖将支持候选人建立一个独立的研究生涯，使用纵向发育神经成像来调查物质使用障碍（SUD）的遗传风险。职业发展培训领域包括：1）功能性磁共振成像（fMRI）方法和统计分析，特别关注儿科神经成像; 2）复杂行为的遗传基础，以及基因-大脑-行为关系; 3）关于精神病理学风险的理论结构; 4）纵向研究方法和统计分析。拟议的研究计划是使用fMRI检查特定的遗传多态性和早期生活压力对儿童SUD风险的神经相关性的贡献。早期的行为和情绪失调都是晚年SUD的强有力预测因素。一个复杂的神经回路，包括纹状体，杏仁核和前额皮质，调节这些过程。拟议的研究计划将在正在进行的UM/MSU纵向研究（R37 AA 07065）中的7至11岁男孩和女孩（n=60）样本中横向研究这些神经系统，并在该样本中以2年为间隔纵向研究这些神经系统。横断面研究将调查早期应激和遗传变异（COMT，SLC 6A 4，MAO-A，TPH，BDNF）对大脑对旨在探测SUD行为风险的任务的反应的影响及其相互作用。纵向研究将调查早期压力和遗传变异对大脑功能反应成熟的影响。它还将开始研究药物使用对大脑发育的影响，以及早期大脑功能反应在确定日后药物滥用问题风险方面的预测价值。拟议的培训和研究活动将为候选人成为专门从事SUD风险纵向发育神经影像学研究的独立研究者奠定坚实的基础。

DESCRIPTION (provided by applicant): This Mentored Research Scientist Development Award will support the candidate in establishing an independent research career using longitudinal developmental neuroimaging to investigate genetic risk for substance use disorders (SUDs). Career development training areas include: 1) Functional magnetic resonance imaging (fMRI) methods and statistical analyses with a particular focus on pediatric neuroimaging; 2) The genetic basis of complex behaviors, and gene-brain-behavior relationships; 3) Theoretical constructs regarding risk of psychopathology; and 4) Longitudinal research methods and statistical analyses. The proposed research plan is to examine the contribution of specific genetic polymorphisms and early-life stress on the neural correlates of SUD risk in children using fMRI. Both behavioral and emotional dysregulation at an early age are strong predictors of SUDs later in life. A complex neuronal circuit, including the striatum, amygdala and prefrontal cortex, regulates these processes. The proposed research plan will investigate these neural systems cross-sectionally in a sample of 7 to 11 year old boys and girls (n=60) from the ongoing UM/MSU Longitudinal Study (R37 AA07065), and longitudinally in this sample at 2-year intervals. The cross-sectional study will investigate effects of, and interactions between, early stress and genetic variants (COMT, SLC6A4, MAO-A, TPH, BDNF) on brain responses to tasks designed to probe behavioral risk for SUDs. The longitudinal study will investigate the effects of early stress and genetic variants on the maturation of brain functional responses to these same tasks. It will also begin to address the influence of drug use on brain development, as well as the predictive value of early brain functional responses in identifying risk for later substance abuse problems. The proposed training and research activities will provide a solid foundation for the candidate to become an independent investigator specializing in longitudinal developmental neuroimaging studies of risk for SUDs.