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（SU）和物质使用障碍（SUD）率已达到流行病的比例。一个有效的早期预防策略，针对青少年在高风险的SU/SUD凭借家族史（FH+）将作出重大和具有成本效益的贡献。虽然这种关系还没有得到很好的理解，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 DA 031975;首席研究员：C霍文）已经开始确定认知控制缺陷，行为和神经生物学测量，作为青少年SU/SUD的关键因素。我们的试点研究结果显示，FH+组在神经回路中一直表现出强烈的多动性和连接性降低，这些神经回路被认为在决策，奖励和成瘾中发挥关键作用。这些变化是在个人接触精神活性物质之前观察到的，因此反映了预先存在的脆弱性。因此，我们的试点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（多模态成像），结合三项正式的认知任务，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，其目标是促进开放性问题，同时提高我们对FH+儿童及其神经行为发育的理解。我们将结合联合收割机和最新的神经认知实验室任务，在纵向和方法学上扩展和建立我们的初步研究，利用非临床流行病学样本，该样本已被广泛表征（5 R 01 DA 023733 -05和5 R 01 DA 024029 -05;主要研究者：C. Hoven）。具体而言，我们将：1）确定父母SUD病史（FH+/-）和认知控制的神经行为指标之间的关系2）检查FH+/-状态和认知控制的基线神经行为指标与从青春期早期到青春期中期的问题SU轨迹的随后发作和进展之间的前瞻性关联，3）纵向检查FH+/-状态之间的关联，在认知控制的神经行为指标的发展中，以及从青春期早期到青春期中期有问题的SU轨迹的发作和进展。我们将研究150名青少年早期（12-14岁）的物质幼稚个体，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，这项研究将检查神经行为维度，同时可能是青少年成像研究中的第一次，考虑到已知会导致青少年SU的社会文化背景因素。

 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.