Pathways From Maltreatment to Substance Abuse

描述（由申请人提供）：这个持续的面向患者的研究（K24）中期研究者奖的申请是对项目公告（PA-09-037）的回应。早期虐待和儿童虐待相关的创伤后应激障碍症状与生物应激系统失调、不利的脑成熟和内侧前额皮质功能障碍有关。患有治疗抵抗性物质使用障碍的成年人更有可能有早期创伤史。在以前的发展创伤学工作的基础上，本K24的目的是研究从创伤到药物滥用的神经生物学途径。职业发展计划的目标是：1)发展精神病学遗传学方面的专业知识；2)通过学习FSL，进一步提高候选人对弥散张量成像的认识，并研究早期创伤与白质发育之间的关系，作为腹侧内侧PFC对决策任务激活的预测因素；3)增加候选人在纵向研究统计方面的实践和经验知识；4)通过指导青少年同事进行儿童虐待研究及其与物质使用障碍的关系，强调本研究翻译部分的知识传播。该研究计划与最近资助的NIDA资助“青少年有限与终身持续性SUD的前额叶功能”有关，这是一项脑成像研究，旨在帮助阐明青少年发病物质使用障碍（SUD）进入青年期的持久性（称为生命过程持久性- lcp -SUD）与持久性（称为青春期限制性（AL-SUD））的大脑机制，作为GSMS的一部分。LCP-SUD患者的青春期前SUD风险因素不同，更有可能有早期生活压力（ELS），包括儿童虐待史。因此，这项工作是PI之前在虐待心理生物学方面的研究的发展成果。我们将检查ELS和遗传因素，以验证ELS和候选遗传标记可能损害前额皮质（PFC）功能从而增加LCP-SUD风险的假设。

DESCRIPTION (provided by applicant): This continuing Midcareer Investigator Award in Patient-Oriented Research (K24) application is in response to program announcement (PA-09-037). Early maltreatment and pediatric maltreatment-related PTSD symptoms are associated with dysregulation of biological stress systems, adverse brain maturation, and medial prefrontal cortical dysfunction. Adults with treatment resistant substance use disorders are more likely to have histories of early trauma. Building on previous work in developmental traumatology, the aim of this K24 is to investigate the neurobiology of pathways from trauma to substance abuse. The objectives of the career development plan are to: 1) develop expertise in psychiatric genetics; 2) further the candidate's knowledge of diffusion tensor imaging by learning FSL and examining the relationship between early trauma and white matter development as predictors of ventral medial PFC activation to decision making tasks in our Great Smoky Mountains Study (GSMS) subjects; 3) increase the candidate's practical and empirical knowledge in the statistical aspects of longitudinal studies; and 4) emphasize knowledge dissemination of the translational components of this research by mentoring junior colleagues in child maltreatment research and its relationship to substance use disorders. The research plan is linked to a recently funded NIDA grant "Prefrontal Function in Adolescent Limited vs. Life Course Persistent SUD," a brain imaging study to help elucidate the brain mechanisms of persistence (called life course persistent-LCP-SUD) versus desistence (called adolescence-limited (AL-SUD) of adolescent onset substance use disorder (SUD) into young adulthood as part of the GSMS. Those with LCP-SUD differed in their preadolescent risk factors for SUD and were more likely to have early life stress (ELS) including histories of child maltreatment. Thus this work is a developmental outgrowth of the PI's previous research in the psychobiology of maltreatment. We will examine ELS and genetic factors to test the hypotheses ELS and candidate genetic markers may impair prefrontal cortex (PFC) function increasing the risk for LCP-SUD. PUBLIC HEALTH RELEVANCE: The intergenerational transmission of child maltreatment and substance abuse are important public health problems. In adults, histories of child maltreatment are associated with persistence of substance use disorders. Understanding the effects of early trauma and genetics on white matter development will help us better understand causal mechanisms that may lead to interventions.