title: Disruption of fetal hormonal programming (prenatal stress) implicates shared risk for sex differences in depression and cardiovascular disease.
abstract: Comorbidity of major depressive disorder (MDD) and cardiovascular disease (CVD) represents the fourth leading cause of morbidity and mortality worldwide, and women have a two times greater risk than men. Thus understanding the pathophysiology has widespread implications for attenuation and prevention of disease burden. We suggest that sex-dependent MDD-CVD comorbidity may result from alterations in fetal programming consequent to the prenatal maternal environments that produce excess glucocorticoids, which then drive sex-dependent developmental alterations of the fetal hypothalamic-pituitary-adrenal (HPA) axis circuitry impacting mood, stress regulation, autonomic nervous system (ANS), and the vasculature in adulthood. Evidence is consistent with the hypothesis that disruptions of pathways associated with gamma aminobutyric acid (GABA) in neuronal and vascular development and growth factors have critical roles in key developmental periods and adult responses to injury in heart and brain. Understanding the potential fetal origins of these sex differences will contribute to development of novel sex-dependent therapeutics.
authors.affiliation: Departments of Psychiatry and Medicine, Harvard Medical School, Boston, MA, USA; Brigham and Women's Hospital (BWH), Connors Center for Women's Health & Gender Biology, 1620 Tremont St. BC-3-34, Boston, MA 02120, USA; BWH, Departments of Psychiatry and Medicine, 1620 Tremont St. BC-3-34, Boston, MA 02120, USA. Electronic address: jill_goldstein@hms.harvard.edu.
authors.forename: J M
authors.initials: JM
authors.lastname: Goldstein
authors.affiliation: Department of Basic Medical Sciences, University of Arizona College of Medicine, 425 N. Fifth Street, Phoenix, AZ 85004, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Handa
authors.affiliation: Department of Biomedical Sciences and School of Biomedical Engineering, Colorado State University, 1617 Campus Delivery, Fort Collins, CO 80523, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Tobet
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000378:metabolism* / Q000503:physiopathology; D003863:Depression / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D047109:Fetal Development / Q000502:physiology*; D006801:Humans; D008297:Male; D012306:Risk; D012727:Sex Characteristics; D013312:Stress, Physiological
keywords: Cardiovascular disease; Depression; Fetal hormonal programming; Hypothalamus; MDD–CVD comorbidity; Prenatal stress; Sex differences