Pathways From Maltreatment to Substance Abuse

描述(由申请人提供)：这项以患者为中心的研究(K24)持续职业生涯中期研究人员奖的申请是对计划公告(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调节失调、大脑发育不良和内侧前额叶皮质功能障碍有关。患有治疗抗药性物质使用障碍的成年人更有可能有早期创伤史。在发展创伤学以前工作的基础上，这本K24的目的是研究从创伤到药物滥用的神经生物学。职业发展计划的目标是：1)发展精神病学遗传学的专业知识；2)通过学习FSL和检查早期创伤和白质发育之间的关系，作为我们的大烟山研究(GSM)受试者决策任务中腹侧PFC激活的预测因子，进一步提高候选人的扩散张量成像知识；3)增加候选人在纵向研究统计方面的实践和经验知识；以及4)通过指导儿童虐待研究的初级同事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。这项研究计划与最近获得NIDA资助的一项名为“青少年局限性前额叶功能vs.生命过程持续性SUD”的脑成像研究有关，该研究旨在帮助阐明青春期物质使用障碍(USD)的持续性(称为生命过程持久性-LCP-SUD)与持续性(称为青春期受限(AL-SUD))的大脑机制，作为GSMS的一部分。患有LCP-SUD的人在青春期前患SUD的危险因素不同，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研究的发展成果。我们将检查ELS和遗传因素，以检验ELS和候选遗传标记可能损害前额叶皮质(PFC)功能的假设，增加LCP-SUD的风险。 公共卫生相关性：虐待儿童和滥用药物的代际传播是重要的公共卫生问题。在成年人中，儿童虐待的病史与持续的物质使用障碍有关。了解早期创伤和遗传学对白质发育的影响将有助于我们更好地理解可能导致干预的因果机制。

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.