Cognitive Control in Children of SUD Parents: A Longitudinal Multimodal MRI Study

 描述(由申请人提供)：美国青少年的物质使用率(SU)和物质使用障碍(SUD)已经达到流行的程度。一项有效的早期预防战略，通过家庭病史(FH+)针对SU/SUD高危青少年，将作出重大和具有成本效益的贡献。虽然这种关系尚不清楚，但最近的研究，包括我们自己的NIDA资助的试点研究(SUD和决策：父母和孩子的试点成像研究；R21 DA031975；首席研究员：C Hoven)已经开始确定认知控制方面的缺陷，包括行为和神经生物学方面的衡量，是青少年SU/SUD的关键因素。我们的试验结果显示，FH+组在被认为在决策、奖励和成瘾中发挥关键作用的神经回路中一直存在强烈的多动和连接减少。这些变化是在个人接触精神活性物质之前观察到的，因此反映了先前存在的脆弱性。因此，我们的初步研究结果是令人信服的。拟议的青少年大脑研究(AbStudy)，在基线和36个月时使用MMRI(多模式成像)，结合三个正式的认知任务，以及以发展为导向的研究设计，包括每三个月进行一次评估，目标是在促进我们对FH+儿童及其神经行为发育的理解的同时，促进开放问题的提出。我们将结合尖端的MMRI和最新的神经认知实验室任务，在纵向和方法论上扩展和建立我们的先导研究，利用已被广泛表征的非临床、流行病学样本(5R01DA023733-05和5R01DA024029-05；首席研究员：C.Hoven)。具体地说，我们将：1)确定父母在青春期早期的SUD病史(FH+/-)与认知控制的神经行为指标(行为和脑结构/功能)之间的关系；2)研究FH+/-状态和基线认知控制神经行为指标与随后从青春期早期到青春期中期问题SU轨迹的发生和进展之间的预期关联；3)研究FH+/-状态与问题SU轨迹从青春期早期到青春期中期的发生和发展之间的纵向关联。我们将研究150名物质幼稚的个体，从青春期早期(12-14岁)开始，他们同样来自FH+/FH-家庭，并跟踪他们到青春期中期(15-17岁)。重要的是，这项研究将同时检查神经行为维度，同时，可能是第一次在青少年成像研究中，考虑到社会文化背景因素，已知对青春期SU有贡献。

 DESCRIPTION (provided by applicant): Rates of substance use (SU) and substance use disorders (SUD) among adolescents in the US have reached epidemic proportions. An effective early prevention strategy that targets adolescents at high risk for SU/SUD by virtue of family history (FH+) would make a significant and cost-effective contribution. While this relationship is not yet well understood, recent research, including our own NIDA-funded Pilot Study (SUD and Decision-Making: A Pilot Imaging Study of Parents and Children; R21 DA031975; Principal Investigator: C Hoven) has begun to identify deficits in cognitive control, measured both behaviorally and neurobiologically, as key factors involved in adolescent SU/SUD. Our Pilot findings reveal consistently strong hyperactivity and reduced connectivity in the FH+ group in neural circuits thought to play key roles in decision making, reward and addiction. These changes are observed prior to an individuals' exposure to psychoactive substances, thus, reflecting pre- existing vulnerabilities. The findings from our Pilot Study are therefore compellin. The proposed Adolescent Brain Study (ABStudy), using MMRI's (multimodal imaging) at baseline and at 36 months, combined with three formal cognitive tasks, and a developmentally-oriented study design, which includes assessments every three months, has the goal of contributing to the open questions while improving our understanding of FH+ children and their neurobehavioral development. We will combine cutting edge MMRI with the latest neurocognitive laboratory tasks to extend and build upon our Pilot Study, both longitudinally and methodologically, drawing on a non-clinical, epidemiological sample, which has been extensively characterized (5R01DA023733-05 and 5R01DA024029-05; Principal Investigator: C. Hoven). Specifically, we will: 1) Identify the relationship between parental SUD history (FH+/-) and neurobehavioral indicators of cognitive control (behavioral and brain structure/functioning) in their children during early adolescence, 2) Examine the prospective association between FH+/- status and baseline neurobehavioral indicators of cognitive control with subsequent onset and progression of problematic SU trajectories from early adolescence through mid- adolescence, 3) Examine longitudinally associations between FH+/- status, in the development of neurobehavioral indicators of cognitive control, and onset and progression of problematic SU trajectories from early adolescence through mid-adolescence. We will study 150 substance naïve individuals, from early adolescence (ages 12-14), who come equally from FH+/FH- families, and follow them through mid-adolescence (ages 15-17). Importantly, this study will examine the neurobehavioral dimensions while simultaneously, possibly for the first time in an adolescent imaging study, taking into account socio-cultural contextual factors, known to contribute to adolescent SU.