Chronic Stress of Maltreatment: Drug Use Vulnerability

描述（由申请人提供）：NIDA长期以来的使命是确定慢性压力对物质使用、滥用和成瘾的影响。该应用程序以多种创新方式解决了这一重要目标。特别是，我们专注于经历儿童虐待，严重和慢性应激源有助于适应不良，精神病理学，物质使用和滥用整个生命过程的高风险的历史后期青少年。虽然许多研究已经确定了虐待儿童与青少年和成年期药物使用之间的联系，但虐待儿童的长期压力导致药物使用和滥用的发展机制只得到很少的关注。众所周知，虐待儿童会损害生物和心理系统，因此必须调查虐待和忽视儿童的这些发展后果如何促成药物滥用结果的出现。 在本申请中，我们正在寻求更新我们以前的调查，在一个物质使用最少的时期，研究了一个不同的青少年前虐待和非虐待儿童的队列。我们建议在青春期后期/成年初，即药物滥用正常升级的时期，对这一样本儿童进行随访。我们将利用原始研究中获得的坚实的发展基础，该研究对虐待和非虐待儿童的多层次影响（社会情感、人际关系、家庭关系、社会背景、个性、精神病理学、注意力、神经认知和神经内分泌）进行了广泛的评估。在本申请中将继续对不同领域进行多级评估。我们还将包括遗传采样，以调查潜在的保护性与风险促进遗传变异对青少年后期药物滥用结果的影响，以及依赖于暴露于儿童虐待的差异效应。我们将对晚期青少年进行各种多层次的评估，并从照顾者和最好的朋友那里获得关于晚期青少年功能的观点。 评估慢性压力对压力敏感系统的影响，在早期，更远的发展阶段，以及在青春期后期整合远端和近端适应慢性压力的能力，有可能大大扩大对慢性压力对药物滥用的多层次影响的理解。这项研究将对公共卫生产生重要影响。除了增进对药物使用和滥用的多层次发展根源的了解外，这项研究还将为预防和干预战略提供重要指导。鉴于有可能确定从虐待儿童到药物滥用的多种途径，将阐明对不同干预目标的见解。 公共卫生相关性：虐待儿童在整个生命过程中对适应不良、精神病理学、药物使用和滥用构成重大风险，因此构成重大公共卫生问题。建议的多层次的，发展的后续调查的青少年后期，没有虐待和忽视儿童的历史将扩大与慢性压力的儿童虐待对压力敏感的生物和心理系统，涉及药物滥用的不良影响的理解。通过增加对导致药物滥用的多层次发展过程的认识，该研究将为预防和干预提供重要方向，具有高度的公共卫生意义。

DESCRIPTION (provided by applicant): NIDA has had a long-standing mission to determine the impact of chronic stress on substance use, abuse, and addiction. This application addresses this important objective in multiple, innovative ways. In particular, we focus on late adolescents with histories of experiencing child maltreatment, a severe and chronic stressor contributing to high risk for maladaptation, psychopathology, and substance use and abuse across the life course. Although numerous studies have identified a linkage between child maltreatment and substance use in adolescence and adulthood, the developmental mechanisms through which the experience of the chronic stress of child maltreatment results in substance use and abuse have received only minimal attention. Child maltreatment is known to impair both biological and psychological systems, and it is essential to investigate how these developmental consequences of child abuse and neglect contribute to the emergence of substance abuse outcomes. In the present application, we're seeking a renewal of our previous investigation of a diverse cohort of preadolescent maltreated and nonmaltreated children studied during a period when there is minimal substance use normatively. We propose to follow-up this sample of children in late adolescence/emerging adulthood, a period when substance abuse normatively escalates. We will capitalize on the solid developmental foundation acquired in the original study, which obtained an extensive assessment of multilevel influences (socio- emotional, interpersonal, family relational, social contextual, personality, psychopathology, attentional, neurocognitive, and neuroendocrine) in maltreated and nonmaltreated children. The multilevel assessment of diverse domains will be continued in the present application. We also will include genetic sampling in order to investigate the potential of protective vs. risk promoting influences of genetic variants on late adolescent substance abuse outcomes and differential effects dependent on exposure to child maltreatment. We will conduct diverse multilevel assessments with the late adolescents, as well as obtain perspectives on the late adolescent's functioning from caregivers and best friends. Assessing the effects of chronic stress on stress-sensitive systems at earlier, more distal periods of development, as well as the capacity to integrate both distal and proximal adaptations to chronic stress in late adolescence has the potential to greatly expand understanding of the multilevel impact of chronic stress on drug abuse. This research will have important implications for public health. In addition to advancing knowledge regarding the multilevel developmental roots of substance use and abuse, the research will provide important direction for prevention and intervention strategies. Given that multiple pathways from child maltreatment to substance abuse are likely to be identified, insights into different intervention targets will be elucidated. PUBLIC HEALTH RELEVANCE: Child maltreatment poses substantial risk across the life course for maladaptation, psychopathology, and substance use and abuse and thus constitutes a critical public health concern. The proposed multilevel, developmental follow-up investigation of late adolescents with and without a history of child abuse and neglect will expand understanding of the adverse effects associated with the chronic stress of child maltreatment on stress-sensitive biological and psychological systems that are implicated in substance abuse. Through increasing knowledge of multilevel developmental processes contributing to substance abuse, the research will provide important direction for prevention and intervention and is of high public health significance.