Physiological Stress Reactivity as a Determinant in Co-occurring Alcohol Use and Anxiety Disorder: Diagnosis and Alcohol Use Outcomes

培训：这份导师研究科学家发展奖的申请将确保候选人的 作为酒精使用障碍和合并症领域的独立临床研究者 research.它将为实现下列培训目标提供支助，建立以下方面的专门知识： 酒精使用（AUD）和焦虑（AnxD）障碍中压力的心理生理学评估，2）临床 酒精滥用研究领域的研究，3）先进的统计方法，4）负责任的行为， research.拟议的培训与强有力的专门导师相结合，将确保成功。研究计划： 合并AUD+AnxD是成功治疗AUD的重要障碍。证据表明 应激反应系统（HPA、ANS、CNS）失调与症状发展的重叠 AUD和AnxD。然而，这必须在合并AUD+AnxD中得到系统性证明。整体 目的：识别和前瞻性评估住院AUD患者的应激系统功能， 没有合并AnxD中心假设：同时发生的AnxD对严重程度产生累加效应， 应激系统失调的持续性，促进AUD复发，并通过AnxD-CBT缓解。 具体目的：评价以下因素的影响：1）同时发生的AnxD对生物强制降解系统严重程度的影响 治疗前AUD住院患者中的参数; 2）在应激系统持续性上共存AnxD 治疗后即刻（治疗后）和1个月后（早期）， 3）AnxD-CBT治疗对合并有严重抑郁症的AUD患者的生物应激系统重新调节的影响。 发生AnxD;以及4）生物应激系统响应4个月AUD临床的重新调节变化 结果。创新包括：a）将合并和不合并AnxD的AUD住院患者与健康患者进行比较， 对照以鉴定AnxD共变体对HPA-ANS-CNS应激系统失调的影响; B） 将应激系统失调的严重性和持续性确定为AUD恢复的生物标志物， 合并AUD+AnxD; c）采用多个评估时间点，以及d）确定AnxD-CBT是否 治疗使受到干扰的压力系统正常化，而治疗后禁欲期间的重新调节预示着 4个月后的治疗结果。该研究具有重要意义，因为：a）添加剂的鉴定 AUD+AnxD与单独AUD的压力系统失调将提供一个综合的生物系统 一种补充AUD+AnxD共病的描述性基于EEG的诊断的方法，和B）验证 共病AUD+AnxD中应激系统再调节受AUD治疗调节并预测AUD 复苏将促进干预措施的发展。总结：上述活动将使 候选人建立职业生涯作为一个独立的科学家谁是装备精良，以获得研究资金， 与同事合作进行双向转化研究，并为实现重大目标做出贡献。 该领域的进展。

Training: This application for a Mentored Research Scientist Development Award will assure the candidate's development as an independent clinical investigator in the field of alcohol use disorder and comorbidity research. It will provide support to accomplish the following training objectives establishing expertise in: 1) psychophysiological assessment of stress in alcohol use (AUD) and anxiety (AnxD) disorders, 2) clinical research in the field of alcohol abuse research, 3) advanced statistical methods, and 4) responsible conduct of research. The proposed training combined with strong dedicated mentors will assure success. Research Plan: Comorbid AUD+AnxD is a significant barrier to successful AUD treatment. Converging evidence implicates overlap in dysregulation of systems governing stress response (HPA, ANS, CNS) for symptom development in AUD and AnxD. However, this must be systematically demonstrated in comorbid AUD+AnxD. The overall objective is identification and prospective assessment of stress system function of AUD inpatients with and without comorbid AnxD. Central Hypothesis: Co-occurring AnxD exerts an additive effect on severity and persistence of stress system dysregulation that promotes relapse in AUD and is mitigated by AnxD-CBT. Specific Aims: Evaluate the effect(s) of: 1) co-occurring AnxD on severity of biological stress system parameters in AUD inpatients at pre-treatment; 2) co-occurring AnxD on persistence of stress system dysregulations in AUD inpatients immediately after treatment (post-treatment) and 1 month later (early abstinence); 3) AnxD-CBT treatment on biological stress system re-regulation among AUD patients with co- occurring AnxD; and 4) re-regulation change in biological stress system responding on 4-month AUD clinical outcomes. Innovation includes: a) comparing AUD inpatients with and without co-occurring AnxD to healthy controls to identify the impact of AnxD comorbidity on HPA-ANS-CNS stress system dysregulation; b) identifying severity and persistence of stress system dysregulation as a biomarker of AUD recovery in comorbid AUD+AnxD; c) employing multiple assessment time points, and d) determining if AnxD-CBT treatment normalizes perturbed stress systems while re-regulation during post-treatment abstinence predicts treatment outcomes 4 months later. The proposed research is significant because: a) identification of additive stress system dysregulation in AUD+AnxD vs. AUD alone will provide an integrated, biological systems approach to supplement descriptive symptom-based diagnoses of comorbid AUD+AnxD and b) validating that stress system re-regulation in comorbid AUD+AnxD is modulated by AUD treatment and predicts AUD recovery will facilitate intervention development. Summary: Together, the foregoing activities will permit the candidate to establish a career as an independent scientist who is well equipped to obtain research funding, collaborate with colleagues in bidirectional translational research, and contribute to making significant advances in the field.