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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23MH064561-02
Application #
6642141
Study Section
Special Emphasis Panel (ZRG1-BBBP-5 (01))
Program Officer
Wynne, Debra K
Project Start
2002-08-05
Project End
2007-07-31
Budget Start
2003-08-01
Budget End
2004-07-31
Support Year
2
Fiscal Year
2003
Total Cost
$167,293
Indirect Cost
Name
University of Pittsburgh
Department
Psychiatry
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Gordon, Jennifer L; Girdler, Susan S; Meltzer-Brody, Samantha E et al. (2015) Ovarian hormone fluctuation, neurosteroids, and HPA axis dysregulation in perimenopausal depression: a novel heuristic model. Am J Psychiatry 172:227-36
Moses-Kolko, Eydie L; Price, Julie C; Wisner, Katherine L et al. (2012) Postpartum and depression status are associated with lower [[¹¹C]raclopride BP(ND) in reproductive-age women. Neuropsychopharmacology 37:1422-32
Moses-Kolko, Eydie L; Perlman, Susan B; Wisner, Katherine L et al. (2010) Abnormally reduced dorsomedial prefrontal cortical activity and effective connectivity with amygdala in response to negative emotional faces in postpartum depression. Am J Psychiatry 167:1373-80
Bogen, Debra L; Hanusa, Barbara H; Moses-Kolko, Eydie et al. (2010) Are maternal depression or symptom severity associated with breastfeeding intention or outcomes? J Clin Psychiatry 71:1069-78
Wisner, Katherine L; Sit, Dorothy K Y; Hanusa, Barbara H et al. (2009) Major depression and antidepressant treatment: impact on pregnancy and neonatal outcomes. Am J Psychiatry 166:557-66
Moses-Kolko, Eydie L; Berga, Sarah L; Kalro, Brinda et al. (2009) Transdermal estradiol for postpartum depression: a promising treatment option. Clin Obstet Gynecol 52:516-29
Moses-Kolko, Eydie L; Wisner, Katherine L; Price, Julie C et al. (2008) Serotonin 1A receptor reductions in postpartum depression: a positron emission tomography study. Fertil Steril 89:685-92
Moses-Kolko, Eydie L; Price, Julie C; Thase, Michael E et al. (2007) Measurement of 5-HT1A receptor binding in depressed adults before and after antidepressant drug treatment using positron emission tomography and [11C]WAY-100635. Synapse 61:523-30
Moses-Kolko, Eydie L; Bogen, Debra; Perel, James et al. (2005) Neonatal signs after late in utero exposure to serotonin reuptake inhibitors: literature review and implications for clinical applications. JAMA 293:2372-83
Moses-Kolko, Eydie L; Berga, Sarah L; Greer, Phil J et al. (2003) Widespread increases of cortical serotonin type 2A receptor availability after hormone therapy in euthymic postmenopausal women. Fertil Steril 80:554-9