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

描述(由申请者提供)：我们的社会因药物滥用和精神病理学等疾病而付出的人力和经济代价令人震惊。表达这些有害的心理社会后遗症的一条途径是通过混乱的监管系统。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唤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据可查的生理标志。因此，这项研究的主要目标之一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。我们还知道，患有精神分裂症(PCE)的儿童成长于严重的早期生活压力和环境风险的背景下。因此，我们将包括对环境风险的衡量，以确定PCE是否是不利结果的重要贡献者，还是仅仅是一个标志。这项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相关的概念。我们最终计划确定一些患有PCE的儿童发展成精神病和使用非法物质的发育途径。数据来自母亲生活方式研究(MLS)，这是对患有PCE的儿童进行的最大纵向出生队列研究。这项拟议的研究包括大约1000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部位MLS接受跟踪。分别在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。具体目的是：a)使用潜在生长曲线建模(LGCM)来检验患有和不患有PCE的儿童从婴儿期到青春期的VT轨迹；b)调查环境风险指数作为VT成长轨迹的预测因子，以解释儿童生理轨迹的个体差异；以及c)使用结构方程模型来测试VT与患有PCE和不患有PCE的儿童的神经行为去抑制之间的发展模型。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，以及由此暗示的其他物质，放在从包括出生后环境逆境影响的发展角度研究产前应激的更广泛的角度。这项研究直接针对NIDA 2010年的战略目标，即通过了解生物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。 与公共卫生相关：我们的社会因药物滥用和精神病理等疾病而付出的人力和经济代价令人震惊。了解有没有产前接触可卡因的儿童的行为问题的生理过程和环境相关性，将有助于更好地确定有可能发展成精神病理学和药物使用的儿童。这些知识反过来可能导致干预研究和项目的发展，以防止药物滥用和精神病理学的发生。

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.