Optimizing Exercise for the Treatment of Anxiety

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PROJECT SUMMARY/ABSTRACT Anxiety disorders are impairing and amongst the most common psychiatric conditions; yet, many impacted individuals do not receive or respond to evidence-based care. There is thus a great need to develop and optimize additional first-line, more accessible interventions for anxiety disorders. Exercise has benefits for anxiety and physical health, without many of the side effects, accessibility issues, or costs of medications or psychotherapy. However, adherence to exercise recommendations is low, and even worse for high intensity exercise (HIE) in individuals with anxiety disorders. This may be due to high anxiety sensitivity (AS), or fear of anxiety-related physiological sensations, as HIE may induce similar sensations. There are, however, no formal guidelines for optimal intensity or titration of exercise for any mental health condition, and it remains unclear whether exercise requires slower titration for optimal tolerability and response for anxiety. In order to develop exercise as a formally prescribed intervention for anxiety disorders in a way that enhances engagement and adherence, research is needed to guide optimal titration of exercise prescriptions, and to establish mechanisms that should be targeted to optimize outcomes in practice. Addressing these gaps, this study will examine the impact of exercise titration on AS/anxiety symptom severity as well as engagement and adherence. Specifically, 90 sedentary adults with a primary anxiety disorder and moderate to high AS will be randomized to either 8 weeks of 1) low intensity exercise, or 2) flexible titration to HIE. Blinded, validated clinician-rated and patient-rated outcomes will be assessed over treatment and at 1- and 3-month follow-up. To better understand what mechanisms influence decisions to exercise in the real-world, and novel to this research and key training goals, are the use of heart rate (HR) as an objective mechanistic target for exercise intensity, examining changes in valuation of exercise through a neuroeconomics task, and the integration of ecological momentary assessment (EMA) to measure effects of immediate changes in mood with exercise on anxiety outcomes and adherence. Additional training goals will support the analysis of study data with state-of- the-art advanced statistical techniques such as growth curve modelling and machine learning. The scientific aims of this study map onto my training plan in three primary areas: 1) applying an NIMH experimental therapeutics approach, integrating an objective target mechanism (HR) and transdiagnostic AS, 2) examining EMA data with HR to identify real time drivers of engagement and response outside the office setting, and 3) applying advanced computational psychiatry techniques to data analysis. Related training goals will enable integration of neuroeconomic human decision-making models into the current study and integral training in neural mechanisms of action to support future R-level proposals. Finally, mentorship from Drs. Simon (primary mentor), Abrantes (Co-mentor), and Glimcher, Jay, Laska, and Pine (advisors) will propel me toward an independent research career focused on optimizing exercise interventions for mental health.