The Impact of Prenatal Cocaine Exposure, Environmental Risk, and Trajectories

描述（由申请人提供）：我们的社会对药物滥用和精神病理学等疾病的人力和财政成本是惊人的。这些有害的心理社会后遗症可能通过一种途径表现出来，那就是调节系统受到破坏。然而，很少有人知道这种失调的生理基础。coconut可能会破坏调节唤醒和注意力的神经系统，从而影响情绪调节的生理标志物。迷走神经张力（VT）是生物体自我调节能力的一个有据可查的生理标志。因此，本研究的广泛目标之一是检查产前暴露（PCE）是否影响基线VT和VT对认知挑战的反应。我们还知道，患有（PCE）的儿童在早期生活压力和环境风险的背景下长大。因此，我们将包括环境风险的措施，以确定PCE是否是一个重要的贡献者或仅仅是一个标志的不利后果。拟议研究的另一个广泛目标是研究从产前可卡因暴露到青春期神经行为去抑制的途径，这是一个与物质使用和精神病理学有关的结构。我们最终计划确定一些PCE儿童发展精神病理学和使用非法物质的发展途径。数据来自孕产妇生活方式研究（MLS），这是PCE儿童最大的纵向出生队列研究。拟议的研究包括大约1,000名患有和不患有PCE的受试者，这些受试者自出生以来一直在多中心MLS中接受随访。在第1、4、12和18个月以及第2-7、11和15年测量基线VT和VT对认知挑战的反应。在整个童年和青春期的精神病理学和物质使用的措施进行管理。具体目标是：a）使用潜在生长曲线模型（LGCM）来检查有和没有PCE的儿童样本中从婴儿期到青春期的VT轨迹; B）调查环境风险指数作为VT中生长轨迹的预测因子，以解释儿童生理轨迹的个体差异;和c）使用结构方程模型来测试有和没有PCE的儿童中VT与神经行为去抑制相关的发展模型。这项拟议的研究将产生很大的影响，因为它将我们对PCE的理解，并暗示其他物质，从发展的角度，包括产后环境逆境的影响，在更广泛的角度研究产前压力。这项研究直接涉及NIDA 2010年的战略目标，即通过了解生物学和发育如何影响药物滥用的风险和预测因素来防止开始使用药物。 公共卫生相关性：我们社会为药物滥用和精神病理学等疾病付出的人力和财政代价是惊人的。知识的生理过程和环境相关的行为问题的儿童与产前可卡因暴露和不允许更好地识别儿童的精神病理学和物质使用的发展风险。这种知识反过来可能导致干预研究和方案的发展，以防止药物滥用和精神病理学的发病。

DESCRIPTION (provided by applicant): The human and financial cost to our society for disorders such as substance abuse and psychopathology is staggering. One pathway by which these deleterious psychosocial sequelae may be expressed is through disrupted regulatory systems. However, little is known about the physiological underpinnings of this dysregulation. Cocaine might disrupt the neural systems that regulate arousal and attention, thereby impacting physiological markers of emotion regulation. Vagal Tone (VT) is a well-documented physiological marker of the organisms' ability to self-regulate. Thus, one of the broad goals of this research is to examine whether Prenatal Cocaine Exposure (PCE) impacts baseline VT and VT reactivity to cognitive challenge. We also know that children with (PCE) grow up in contexts of significant early life stress and environmental risk. We will therefore include measures of environmental risk to determine if PCE is a significant contributor to or simply a marker for adverse outcome. Another broad goal of the proposed research is to study pathways from prenatal cocaine exposure to neurobehavioral disinhibition in adolescence, a construct that is related to substance use and psychopathology. We ultimately plan to identify developmental pathways by which some children with PCE develop psychopathology and use illicit substances. Data come from the Maternal Lifestyle Study (MLS), the largest longitudinal birth cohort study of children with PCE. The proposed study includes approximately 1,000 subjects with and without PCE who have been followed since birth in the multisite MLS. Baseline VT and VT response to cognitive challenge was measured at 1, 4, 12, and 18 months and at years 2-7, 11, and 15. Across childhood and adolescence measures of psychopathology and substance use were administered. The specific aims are to: a) use Latent Growth Curve Modeling (LGCM) to examine trajectories of VT from infancy to adolescence in a sample of children with and without PCE; b) investigate indices of environmental risk as predictors of growth trajectories in VT to account for individual differences in children's physiological trajectories; and c) use Structural Equation Modeling to test a developmental model relating VT to neurobehavioral disinhibition among children with and without PCE. The proposed study will have a high impact because it places our understanding of PCE, and by implication other substances, in the broader perspective of research on prenatal stress from a developmental perspective that includes the effects of postnatal environmental adversity. This study directly addresses the NIDA 2010 strategic goal to prevent the initiation of drug use by understanding how biology and development influence the risk and predictive factors for drug abuse. PUBLIC HEALTH RELEVANCE: The human and financial cost to our society for disorders such as substance abuse and psychopathology is staggering. Knowledge regarding physiological processes and environmental correlates of behavior problems among children with and without prenatal cocaine exposure will permit better identification of children at risk for the development of psychopathology and substance use. This knowledge in turn may lead to the development of intervention research and programs to prevent the onset of substance abuse and psychopathology.