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

培训：这份申请导师研究科学家发展奖的申请书将确保候选人 发展为酒精使用障碍和共病领域的独立临床调查者 研究。它将为实现以下培训目标提供支持，建立以下方面的专门知识：1) 酒精使用应激(AUD)和焦虑(AnxD)障碍的心理生理学评估，2)临床 酒精滥用研究领域的研究，3)先进的统计方法，以及4)负责任的行为 研究。拟议的培训与强有力的敬业导师相结合，将确保成功。研究计划： AUD+AnxD并存是成功治疗AUD的重要障碍。 应激反应调控系统(HPA、ANS、CNS)在症状发展中的重叠 AUD和ANXD。然而，这必须在并存的AUD+ANXD中得到系统的证明。整体而言 目的是识别和前瞻性评估AUD住院患者的应激系统功能。 没有共病的AnxD。中心假说：共发病的AnxD对严重程度和 持续的应激系统失调促进了AUD的复发，并通过AnxD-CBT缓解。 具体目标：评估(S)：1)共生ANXD对生物应激系统严重程度的影响 AUD住院患者治疗前的参数；2)共生ANXD对应激系统持续性的影响 AUD住院患者在治疗后即刻(治疗后)和1个月后(早期)的调节障碍 3)AnxD-CBT治疗对AUD患者生物应激系统的再调节作用 发生AnxD；4)AUD临床4个月时生物应激系统反应的再调节变化 结果。创新包括：a)比较患有和不患有AnxD的AUD住院患者与健康患者 对照，以确定AnxD共病对HPA-ANS-CNS应激系统失调的影响；b) 确定应激系统失调的严重性和持久性作为AUD恢复的生物标志物 AUD+ANXD并存；c)使用多个评估时间点，以及d)确定ANXD-CBT 治疗使不安的压力系统正常化，而治疗后戒断期间的重新调节预示着 4个月后的治疗结果。拟议的研究具有重要意义，因为：a)添加剂的鉴定 AUD+AnxD与AUD相比的应激系统失调将提供一个完整的生物系统 补充基于描述性症状的AUD+AnxD诊断的方法和b)验证 AUD+AnxD共病的应激系统再调节受AUD治疗的调制并预测AUD 复苏将促进干预发展。摘要：上述活动加在一起将使 作为一名独立科学家建立职业生涯的候选人，他有能力获得研究资金， 在双向翻译研究中与同事协作，并为做出重大贡献做出贡献 该领域的进步。

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.