This revised Mentored Patient-Oriented Research Career Development Award Application (K23 describes a program of training and research using positron emission tomography (PET) to identify neurobiological processes mediating women's depressive syndromes that occur at reproductive transitions. Career development activities will focus on PET advanced analysis and modeling techniques reproductive endocrinology, cellular and molecular neuroscience, Psychiatric assessment, and clinical research design and statistical methods. These skills will be applied to the study of serotonin-IA (5HT1A receptor binding potential (BP) and resting cerebral blood flow (CBF) in DSM-lV-defined major depressive disorder (MDD) with postpartum onset. The association of female gonadal steroids (FGS with MDD and its treatment suggests FGS are important mediators of depressive disorders in women Because postpartum major depression (PPD) occurs in the setting of massive endocrine shifts, this provides a unique opportunity to explore the neurobiology of depressive syndromes that occur a reproductive transitions. Based upon existing characterization in the literature and in our PET Facility of depressive populations using probes for 5HT1A receptor BP ([11C] WAY-100635) and CBF ([15O] water) methods for measuring these targets will be applied in women with PPD, non-postpartum MDD postpartum healthy controls, and non-postpartum healthy controls. Hypothalamic-pituitary-ovarian (HPO and hypothalamic-pituitary-adrenal (HPA) axis function will be assessed in relation to PET measures Multidisciplinary didactic training, research experience, and preliminary data garnered from the proposed application will enable the candidate to become an independent investigator of the neurobiology of depressive syndromes associated with reproductive transitions.
