Biological Mechanisms of Perinatal Anxiety

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PROJECT SUMMARY/ABSTRACT This is an application for a Mentored Patient-Oriented Research Career Development Award. The goal of the proposed project is to provide me with the advanced training necessary to establish an independent program of research in perinatal psychiatric disorders, and specifically in the contributions of immunological and endocrinological factors to perinatal psychopathology. To facilitate this long-term career goal, I will examine biological correlates of anxiety across pregnancy and the postpartum. I propose a comprehensive training plan, combining formal coursework in immunology and biostatistics with individual mentor meetings, applied training experiences, and participation in conferences, seminars, and workshops. Specific short-term training goals include: 1) Develop expertise in the psychoneuroimmunology of pregnancy and the postpartum 2) Gain a fuller understanding of reproductive hormonal physiology 3) Improve my understanding of biostatistics and epidemiology and develop a solid understanding of longitudinal data analysis 4) Refine my skill in measuring perinatal anxiety by learning how to administer laboratory stressors to pregnant women and measure the resultant autonomic reactivity and 5) Become adroit at integrating information about perinatal anxiety across numerous RDoC units of analysis, including cells, physiology, behaviors, self-reports, and paradigms. The training plan will be executed in conjunction with a proposed set of research studies based on preliminary data that I have collected and/or analyzed. These data demonstrate a relationship between inflammatory cytokines and TRAIT anxiety in pregnancy; between pro-inflammatory cytokines and STATE anxiety across the perinatal period; between allopregnanolone and obsessive symptoms in pregnancy; and between allopregnanolone in pregnancy and subsequent postpartum affective symptoms. The proposed research will build upon these preliminary findings by prospectively following a cohort of anxious pregnant women and healthy matched controls; by analyzing their blood samples for inflammatory cytokines, immune cells, and allopregnanolone; and by measuring maternal reactivity to a validated pregnancy-specific laboratory task that will measure attentional bias to threat and act as a stimulus for autonomic arousal.