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

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.