Mechanisms Underlying the Relationship between Sleep Problems and Drug Use in Ado

描述（由申请人提供）：提出的纵向R01研究将阐明青少年睡眠问题与药物/酒精使用倾向之间关系的机制。考虑到药物前暴露基线的前瞻性研究很少，而且缺乏综合模型，这种假定的关系仍然存在许多问题。需要一种系统的方法来检查睡眠障碍和药物滥用之间的内在联系、时间动态和机制。我们的综合时间模型理论认为，睡眠问题将是青少年开始使用药物/酒精和使用升级的重要预测因素。我们进一步提出，这种关系至少可以部分地通过情绪失调来解释，正如通过涉及情感边缘结构的任务和神经内分泌（皮质醇）功能的扰动来测量的那样，认知功能水平受到睡眠问题和压力的影响，并与情绪失调和药物滥用风险相关，将缓和睡眠问题和药物使用之间的关系。暴露于长期的压力（如虐待、忽视、离婚、贫穷），预计会扩大中介关系，因为它已被证明会诱发情绪失调，扰乱睡眠，并影响药物滥用风险和复发。性别和青春期发展也将包括在这些模型中，因为据报道，睡眠问题比女孩更能预测男孩开始吸毒，而且男女的青春期发展都与较差的睡眠质量和持续时间有关。最后，该模型预测，最终的药物使用将加剧睡眠问题，导致睡眠、情绪调节和认知能力的进一步下降，促进不断升级的使用模式。我们有一个独特的机会来研究这些关系，通过访问参与者（529对亲子二人组），在一个使用率很高的社区进行前所未有的药物使用纵向前瞻性研究（重点是大麻，青少年最常用的非法药物）。基线数据是在青少年10-12岁时收集的，最后一波数据收集即将完成，青少年年龄在12-14.5岁之间。这项资助的研究旨在确定大麻使用与其他药物和不使用轨迹的神经认知前体和后果。对这些儿童进行评估的方法包括终生压力暴露、睡眠习惯和问题、智商、ECF、情绪调节、行为问题、精神障碍和药物/酒精使用（仅包括基线时的青少年药物和酒精摄入量）。拟议的研究将延长另外两个28个月的数据收集周期，直到青少年后期（直到~18-20岁），这时药物使用的途径变得越来越清晰，过渡到升级的使用模式已经浮出水面，并且使用的后果变得明显。为了检验提出的假设，我们将添加皮质醇采样、睡眠日志、睡眠活动记录仪和关于孩子睡眠模式的家长问题。如果儿童时期的睡眠问题确实增加了药物使用和治疗困难的可能性，那么考虑到这些功能的可塑性，父母、教师和临床医生对儿童和青少年睡眠问题的潜在原因给予更多的关注，将具有重要的预防和/或改善长期影响。

DESCRIPTION (provided by applicant): The proposed longitudinal R01 study will elucidate mechanisms underlying the relationship between sleep problems and propensity to drug/alcohol use in adolescents. Many questions remain about this putative relationship given that prospective studies with a pre-drug exposure baseline are few and integrative models are lacking. A systems approach is needed that examines the inherent linkages, temporal dynamics, and mechanisms in the relationship between sleep disturbances and drug abuse. Our integrative, temporal model theorizes that sleep problems will be significant predictors of drug/alcohol initiation and escalation of use in adolescents. We propose further that this relationship can be explained at least in part by emotion dysregulation, as measured by tasks that recruit affective limbic structures and perturbations in neuroendocrine (cortisol) functioning Level of cognitive functioning, which is affected by sleep problems and stress and is associated with emotional dysregulation and risk for drug abuse, will moderate the relationship between sleep problems and drug use. Exposure to prolonged stress (e.g., maltreatment, neglect, divorce, poverty), is expected to amplify the mediational relationship because it has been shown to induce emotion dysregulation, disrupt sleep, and influence drug abuse risk and relapse. Gender and pubertal development also will be included in these models, given findings that sleep problems are reportedly more predictive of drug use initiation in boys than in girls, and that pubertal development in both sexes is associated with poorer sleep quality and duration. Finally, the model predicts that eventual drug use will exacerbate sleep problems and lead to further decrements in sleep, emotion regulation, and cognition, promoting an escalating pattern of use. We have a unique opportunity to study these relationships by accessing participants (529 parent-child dyads) in an unprecedented ongoing longitudinal, prospective study of drug use (with a focus on marijuana, the most commonly used illicit drug in adolescence) use in a community with a high prevalence of use. Baseline data were collected when youth were aged 10-12 and the last wave of data collection is near completion with youth between 12-14.5 years old. The funded study was designed to identify the neurocognitive precursors and consequences of marijuana use relative to other drug and nonuse trajectories. The children are being assessed using measures of lifetime stress exposures, sleep habits and problems, IQ, ECF, emotion regulation, behavioral problems, psychiatric disorders, and drug/alcohol use (only youth drug and alcohol nave at baseline were included). The proposed study would prolong data collection for two additional 28 month waves into later adolescent years (until ~18-20 years old) when pathways of drug use become increasingly clear, transitions to an escalated pattern of use have surfaced, and consequences of use become apparent. To test the proposed hypotheses, we will add cortisol sampling, sleep log, sleep actigraphy, and parent questions regarding the child's sleep patterns. If sleep problems in childhood indeed increase the probability of onset of drug use and treatment intractability, greater attention by parents, teachers, and clinicians to the underlying causes of sleep problems in children and adolescents would have significant preventive and/or ameliorative long-term implications given the malleability of these functions.