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

描述(由申请人提供)：拟议的R01纵向研究将阐明青少年睡眠问题与吸毒/酗酒倾向之间关系的潜在机制。考虑到以药物前暴露基线为基础的前瞻性研究很少，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、时间动力学和机制。我们的综合时间模型理论认为，睡眠问题将是青少年药物/酒精开始和使用升级的重要预测因素。我们进一步提出，这种关系至少可以通过情绪失调来解释，情绪失调是通过招募情感边缘结构和认知功能的神经内分泌(皮质醇)功能水平的扰动来衡量的，认知功能的扰动会受到睡眠问题和压力的影响，并与情绪调节失调和药物滥用风险有关，将缓和睡眠问题和药物使用之间的关系。长期暴露在压力下(如虐待、忽视、离婚、贫穷)，预计会放大这种调解关系，因为它已被证明会导致情绪失调，扰乱睡眠，并影响药物滥用风险和复发。性别和青春期发育也将包括在这些模型中，因为研究发现，据报道，睡眠问题比女孩更能预测男孩开始吸毒的可能性，而且男女的青春期发育都与较差的睡眠质量和持续时间有关。最后，该模型预测，最终使用毒品将加剧睡眠问题，导致睡眠、情绪调节和认知能力进一步下降，促进使用模式的升级。我们有一个独特的机会来研究这些关系，方法是访问参与者(529名亲子二人)，这是一项史无前例的、持续的、前瞻性的药物使用研究(重点是大麻，青少年最常用的非法药物)，在一个毒品使用率很高的社区。基线数据是在10-12岁的青年收集的，最后一波数据收集在12-14.5岁的青年中接近完成。这项由资金资助的研究旨在确定大麻使用相对于其他毒品和不使用轨迹的神经认知前体和后果。正在使用终生压力暴露、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(仅包括基线水平的青少年药物和酒精)来评估儿童。拟议的研究将再延长两次28个月的数据收集，直到青春期后期(直到~18-20岁)，届时吸毒途径变得越来越清晰，向逐步升级的使用模式的过渡已经浮出水面，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、睡眠记录、睡眠活动记录以及有关儿童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难治性的可能性，父母、教师和临床医生更多地关注儿童和青少年睡眠问题的根本原因，将具有重大的预防和/或改善长期影响，因为这些功能具有可塑性。

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.