In Utero Cocaine Use: Adolescent and Young Adult Neurocognitive Outcome

描述（由申请人提供）：在20世纪80年代末开始的“流行病”期间，在子宫内接触可卡因（COC）的个体现在正在进入青春期和青年期。当这些年轻人在学术领域和工作场所遇到越来越多的要求时，我们不清楚他们会遇到什么样的神经认知障碍（NC）。这项资助的长期目标是探索妊娠期COC暴露对青少年和年轻人NC结果的影响。虽然动物研究压倒性地发现了大脑功能变化的证据，但人类研究却得出了不一致的结果。我们建议通过整合认知神经科学、神经影像学和压力神经科学的概念和方法，来完善产前COC暴露对人类影响的研究。我们将检验三个假设：1)产前COC暴露影响青少年和年轻人的NC结局；2)产前COC暴露对神经发育有影响，可通过神经影像学识别；3)产前COC暴露改变应激反应的调节。在一项为期5年的前瞻性研究中，120名低收入城市非洲裔美国青少年自出生（1989-92）以来一直随访，其中一半有产前COC暴露，一半没有，其中有一个广泛的数据库（包括先前的NC和神经影像学数据），我们将：1)每半年评估一次风险（包括尿药物筛查）并收集人口统计数据；2)两次（早、晚各一次）用神经认知电池评估NC功能，并通过神经影像学研究评估神经发育；3)利用内分泌、自主神经和行为测量评估受试者对应激刺激的反应。统计分析将采用多变量和纵向统计模型（混合效应模型、GEE和潜在轨迹模型）。由于这里调查的队列是最古老的纵向跟踪之一，并且有基线NC和神经影像学数据，我们有一个几乎前所未有的机会，通过应用认知神经科学，最先进的神经影像学和压力神经科学，来检测产前COC暴露对青少年和年轻人的影响。结果将告知预期的障碍，如果有的话，暴露的青年在其人生轨迹的下一个阶段的成功-学术领域和工作场所。了解长期影响有助于制定策略，提高青年的生产力，为他们承担成年后的责任做好准备。

DESCRIPTION (provided by applicant): Individuals exposed to cocaine (COC) in utero during the "epidemic" that began in the late 1980s now are entering adolescence and young adulthood. What neurocognitive (NC) impediments to anticipate, if any, as these young people encounter increasing demands in the academic arena and workplace are unclear. The long-term objective of this grant is exploration of the effects of gestational COC exposure on NC outcome of adolescents and young adults. While animal studies overwhelmingly find evidence of changes in brain function, human studies have yielded inconsistent results. We propose to refine the study of effects of prenatal COC exposure in humans by incorporating concepts and methods from cognitive neuroscience, advances in neuroimaging, and neuroscience of stress. We will test three hypotheses: 1) prenatal COC exposure affects NC outcome in adolescents and young adults; 2) prenatal COC exposure produces effects on neural development identifiable by neuroimaging; and 3) prenatal COC exposure alters the regulation of stress response. In a 5-year prospective study of 120 low income urban African American adolescents followed since birth (1989-92), half with prenatal COC exposure and half without, for whom there is an extensive database (to include prior NC and neuroimaging data), we will: 1) semi-annually assess risk-taking (to include urine drug screens) and collect demographics; 2) twice (once early, once late) assess NC function with a neurocognitive battery, and assess neural development through neuroimaging studies; and 3) on one occasion evaluate subjects' reponses to stressful stimuli using endocrine, autonomic, and behavioral measures. Statistical analyses will employ multivariate and longitudinal statistical models (mixed effect models, GEE, and latent trajectories models). As the cohort investigated here is one of the oldest being followed longitudinally, and for whom there are baseline NC and neuroimaging data, we have an almost unprecedented opportunity, through application of cognitive neuroscience, state of the art neuroimaging, and neuroscience of stress, to detect effects of prenatal COC exposure in adolescents and young adults. Results will inform regarding anticipated obstacles, if any, to the success of exposed youth in the next phases of their life trajectory - the academic arena and work place. Understanding long-term effects allows design of strategies to enhance youths' productivity and prepare them for responsibilities of adulthood.