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

描述（由申请人提供）：药物滥用和精神病理等疾病给我们社会带来的人力和经济成本是惊人的。这些有害的社会心理后遗症可能通过紊乱的调节系统表达。然而，人们对这种失调的生理基础知之甚少。可卡因可能会扰乱调节觉醒和注意力的神经系统，从而影响情绪调节的生理标志。迷走神经张力（VT）是生物体自我调节能力的一个有充分证据的生理标志。因此，本研究的一个广泛目标是检查产前可卡因暴露（PCE）是否影响基线VT和VT对认知挑战的反应。我们也知道，患有PCE的儿童在早期生活压力和环境风险较大的环境中长大。因此，我们将纳入环境风险措施，以确定PCE是不良后果的重要因素还是仅仅是一个标志。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，这是一种与物质使用和精神病理相关的结构。我们最终计划确定一些患有PCE的儿童发展精神病理和使用非法药物的发展途径。数据来自母亲生活方式研究（MLS），这是对PCE儿童进行的最大的纵向出生队列研究，该研究包括大约1000名有或没有PCE的受试者，他们自出生以来一直在多地点MLS中进行随访。在1、4、12和18个月以及2-7、11和15岁时测量基线VT和VT对认知挑战的反应。对儿童和青少年的精神病理学和药物使用进行了测量。具体目的是：a)使用潜在生长曲线模型（LGCM）在有和没有PCE的儿童样本中检查从婴儿期到青春期的VT轨迹；b)研究环境风险指标作为VT生长轨迹的预测因子，以解释儿童生理轨迹的个体差异；c)利用结构方程模型对有PCE和没有PCE的儿童的VT与神经行为去抑制相关的发育模型进行测试。该研究将我们对PCE的理解，以及其他物质的含义，置于从发育角度研究产前压力的更广泛视角，包括出生后环境逆境的影响，这将具有很高的影响。这项研究直接解决了NIDA 2010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预防药物使用的开始。

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.