Prenatal stress-immune programming of sex differences in comorbidity of depression and obesity/metabolic syndrome

Jill M. Goldstein, Laura Holsen, Grace Huang, Bradley D. Hammond, Tamarra James-Todd, Sara Cherkerzian, Taben M. Hale, Robert J. Handa

Research output: Contribution to journalArticle

18 Scopus citations


Major depressive disorder (MDD) is the number one cause of disability worldwide and is comorbid with many chronic diseases, including obesity/metabolic syndrome (MetS). Women have twice as much risk for MDD and comorbidity with obesity/MetS as men, although pathways for understanding this association remain unclear. On the basis of clinical and preclinical studies, we argue that prenatal maternal stress (ie, excess glucocorticoid expression and associated immune responses) that occurs during the sexual differentiation of the fetal brain has sex-dependent effects on brain development within highly sexually dimorphic regions that regulate mood, stress, metabolic function, the autonomic nervous system, and the vasculature. Furthermore, these effects have lifelong consequences for shared sex-dependent risk of MDD and obesity/ MetS. Thus, we propose that there are shared biologic substrates at the anatomical, molecular, and/or genetic levels that produce the comorbid risk for MDD-MetS through sex-dependent fetal origins.

Original languageEnglish (US)
Pages (from-to)425-436
Number of pages12
JournalDialogues in Clinical Neuroscience
Issue number4
StatePublished - 2016



  • Depression
  • Depression-cardiometabolic comorbidity
  • Fetal programming
  • Inflammation
  • Obesity/metabolic syndrome
  • Prenatal stress model
  • Sex difference

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

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