PROJECT SUMMARY Interventions are critically needed to address the maternal mental health crisis in the United States, particularly since mental illness is now the leading cause of maternal mortality. Unprecedented societal shifts, disparities in access to mental health care, stigma, reluctance to use psychiatric medications, and inflammation associated with uncontrolled mental illness all highlight the need for simple, scalable, and equitable solutions in pregnancy. Developing solutions tailored to specific aspects of this problem is an essential first step. However, there is a significant knowledge gap in how mental illness contributes to maternal morbidity and mortality which must first be understood to direct risk reduction strategies. One approach to doing this involves studying severe maternal morbidity (SMM), a composite of severe complications that often precede death yet occur 70 times more frequently. In preliminary work, Dr. Panelli found that the risk of SMM is 58% higher in people with mental illness yet the relative contribution of other factors such as substance use and medical comorbidities to this risk remains to be elucidated. To address these knowledge gaps and prepare for a career as an independent clinician scientist in this field, Dr. Panelli has developed this innovative K23 proposal to reduce SMM due to mental illness through identifiable behavioral and biologic pathways. The Specific Aims are to: 1) Identify casual pathways for increased SMM in people with depression and anxiety – the two most common perinatal mental illnesses – using a population-level approach with Veteran’s Health Administration (VA) data; and 2) Conduct a pilot randomized controlled trial (RCT) of a physical activity intervention in pregnant people with mental illness to reduce severity of depression and/or anxiety and lower stress biomarkers (leukocyte telomere length and hair cortisol). These aims will be conducted in parallel to provide complimentary preliminary data to inform an R01 RCT of a physical activity intervention to reduce SMM in people with mental illness. Dr. Panelli’s training will be conducted under the experienced mentorship of Drs. Carmichael (perinatal epidemiologist), Phibbs (health economist), and Gotlib (clinical psychologist/neuroscientist), in conjunction with advisors in lifestyle interventions (Dr. Pinto) and RCT design (Dr. Lyell). Support from this K23, which will feature content training in perinatal mental illness, hands-on analysis of population-level data with advanced epidemiologic methods, and experience with clinical trials, will advance Dr. Panelli’s long-term goal of becoming an independent clinical researcher with expertise in the complex physical and biological interrelationship between mental illness, pregnancy, and SMM.