PROJECT ABSTRACT Depressive relapse during pregnancy is highly prevalent particularly among women with recurrent depression. Maternal psychiatric morbidity associated with depressive relapse during pregnancy is of concern as is the impact of untreated mood disorder during pregnancy and the postpartum period on child development. While maintenance antidepressant treatment is the standard of care for women with recurrent depression, concerns exist regarding known and unknown effects of fetal exposure to these agents; understandably, many pregnant women and their providers seek non-pharmacologic alternatives to pharmacologic treatment during pregnancy. Mindfulness-based cognitive therapy (MBCT) is efficacious in the prevention of depressive relapse among pregnant women as compared to usual care and is scalable using digital delivery. We propose a pragmatic effectiveness trial comparing MBCT to usual care (UC) among euthymic pregnant women (N=500) with recurrent depression treated with maintenance antidepressants. The study will be conducted at the University of Colorado Boulder (UCB; PI Dimidjian) and Massachusetts General Hospital (MGH; PI Cohen) using the Collaborative RO1 mechanism. This grant mechanism is justified given the unique expertise brought by each site to the proposed investigation. Specifically, the UCB site provides expertise in pragmatic randomized trials and MBCT for pregnant women, and the MGH site provides expertise in prospective monitoring of pregnant women with mood disorders. We will address three primary aims: 1) to examine the relative risk for depressive relapse and reduction of symptom burden between women randomized to digital MBCT or UC; 2) to examine the risk for depressive relapse between women who are randomized to MBCT who discontinue antidepressant treatment and those randomized to UC who discontinue antidepressant treatment, and to apply a treatment selection algorithm to ask what works for whom with respect to MBCT versus antidepressant maintenance; and 3) to examine the extent to which digital MBCT engages key putative targets. Systematic investigation of interventions that can attenuate risk for depressive relapse during pregnancy particularly in “at risk” populations minimizes the morbidity of recurrent depression during critical times in the lives of reproductive aged women.

PROJECT NARRATIVE Depressive relapse during pregnancy is highly prevalent particularly among women with recurrent depression; although maintenance antidepressant treatment is the standard of care, concerns exist regarding known and unknown effects of fetal exposure to these agents. Pregnant women and their healthcare providers express preference for non-pharmacologic options; however, effectiveness for such options, generally and specifically with respect to antidepressant use, has been limited. Mindfulness-based cognitive therapy is efficacious in the prevention of depressive relapse among pregnant women as compared to usual care and is scalable using digital delivery; if proven effective in the proposed trial, the availability of an effective, scalable, non- pharmacologic approach to depressive relapse prevention would guide clinical decision making, expand accessible options, and promote maternal mental health during pregnancy and the postpartum.