Pediatric maltreatment-related PTSD: Psychobiology

描述（由申请人提供）：此面向患者研究（K24）职业中期研究者奖申请是为了响应项目公告（PA-99-133）“职业发展奖：儿童虐待和忽视研究”。儿童虐待相关的创伤后应激障碍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。在先前的发展创伤学研究的基础上，本研究的目的是研究性虐待儿童创伤后应激障碍有效治疗的心理生物学。职业发展计划的目标是：1)发展基于证据的心理社会治疗的专业知识，如认知行为疗法（CBT）和联合精神药物干预治疗受虐待的PTSD儿童；2)进一步发展候选人的发展和认知神经科学知识，强调脑成像测量的整合和翻译，因为它与神经诊断评估和治疗有关；3)增加候选人在治疗开发相关临床试验的实施和设计方面的实践和经验知识，包括进行纵向研究和临床试验的高级研究设计，方法和统计方面；4)通过指导儿童虐待和忽视研究的初级同事，强调该研究的转化部分的知识传播。这项研究计划与一项正在进行的研究有关，该研究使用脑成像技术来帮助阐明患有创伤后应激障碍的性虐待儿童的神经生物学标志物。本研究计划的目的是采用非侵入性生物标志物（24小时尿液皮质醇和儿茶酚胺浓度，内侧前额叶皮层核磁共振成像脑NAA浓度和神经心理功能测量）进行CBT治疗研究，在前后设计中研究30名6至12岁性虐待儿童PTSD的发病机制。还建议在以创伤为重点的CBT +舍曲林和CBT +安慰剂中探索这些生物标志物。

DESCRIPTION (provided by applicant): This Midcareer Investigator Award in Patient-Oriented Research (K24) application is in response to program announcement (PA-99-133) "Career Development Awards: Child Abuse and Neglect Research." Pediatric maltreatment-related PTSD is associated with dysregulation of biological stress systems, adverse brain maturation, and medial prefrontal cortical dysfunction. Building on previous work in developmental traumatology, the aim of this K24 is to investigate the psychobiology of effective PTSD treatment for sexually-abused children. The objectives of the career development plan are to: 1) develop expertise in evidence-based psychosocial treatments i.e., cognitive behavioral therapy (CBT) and combined psychopharmacologic interventions for maltreated children with PTSD, 2) further the candidate's knowledge of developmental and cognitive neuroscience emphasizing the integration and translation of brain imaging measurement as it relates to neurodiagnostic assessment and treatment, 3) increase the candidate's practical and empirical knowledge in the conduct and design of relevant clinical trials for treatment development including advanced research design, methodology and statistical aspects of conducting longitudinal studies and clinical trials, and 4) emphasize knowledge dissemination of the translational components of this research by mentoring junior colleagues in child abuse and neglect research. The research plan is linked to an ongoing study using brain imaging to help elucidate neurobiological markers in sexually abused children with PTSD. The objective of the research plan is a CBT treatment study using non-invasive biological markers (24 hour urinary concentrations of cortisol and catecholamines, MRS-based brain NAA concentrations of medial prefrontal cortex, and measures of neuropsychological functioning), in a pre-post design to investigate the pathogenesis of PTSD in 30 sexually abused children, ages 6 to 12 years. Exploring these biological markers in trauma-focused CBT + Sertraline and CBT + placebo is also proposed.