Neuroscience Bulletin

, Volume 32, Issue 4, pp 398–420 | Cite as

The Immune System and the Role of Inflammation in Perinatal Depression

  • Philippe Leff-Gelman
  • Ismael Mancilla-Herrera
  • Mónica Flores-Ramos
  • Carlos Cruz-Fuentes
  • Juan Pablo Reyes-Grajeda
  • María del Pilar García-Cuétara
  • Marielle Danitza Bugnot-Pérez
  • David Ellioth Pulido-Ascencio


Major depression during pregnancy is a common psychiatric disorder that arises from a complex and multifactorial etiology. Psychosocial stress, sex, hormones, and genetic vulnerability increase the risk for triggering mood disorders. Microglia and toll-like receptor 4 play a crucial role in triggering wide and varied stress-induced responses mediated through activation of the inflammasome; this leads to the secretion of inflammatory cytokines, increased serotonin metabolism, and reduction of neurotransmitter availability along with hypothalamic–pituitary–adrenal axis hyperactivity. Dysregulation of this intricate neuroimmune communication network during pregnancy modifies the maternal milieu, enhancing the emergence of depressive symptoms and negative obstetric and neuropsychiatric outcomes. Although several studies have clearly demonstrated the role of the innate immune system in major depression, it is still unclear how the placenta, the brain, and the monoaminergic and neuroendocrine systems interact during perinatal depression. Thus, in the present review we describe the cellular and molecular interactions between these systems in major depression during pregnancy, proposing that the same stress-related mechanisms involved in the activation of the NLRP3 inflammasome in microglia and peripheral myeloid cells in depressed patients operate in a similar fashion in the neuroimmune placenta during perinatal depression. Thus, activation of Toll-like receptor 2 and 4 signaling and the NLRP3 inflammasome in placental immune cells may promote a shift of the Th1/Th2 bias towards a predominant Th1/Th17 inflammatory response, associated with increased secretion of pro-inflammatory cytokines, among other secreted autocrine and paracrine mediators, which play a crucial role in triggering and/or exacerbating depressive symptoms during pregnancy.


Depression Pregnancy Immune system Inflammation Cytokine Serotonin Indoleamine 2,3 dioxygenase Glucocorticoid Brain Placenta 



This review was supported by the National Institute of Perinatology, Mexico City (234560) and FONSEC SSA/IMSS/ISSSTE 2015-1 (261435).


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Copyright information

© Shanghai Institutes for Biological Sciences, CAS and Springer Science+Business Media Singapore 2016

Authors and Affiliations

  • Philippe Leff-Gelman
    • 1
  • Ismael Mancilla-Herrera
    • 1
  • Mónica Flores-Ramos
    • 2
    • 5
  • Carlos Cruz-Fuentes
    • 2
  • Juan Pablo Reyes-Grajeda
    • 3
  • María del Pilar García-Cuétara
    • 4
  • Marielle Danitza Bugnot-Pérez
    • 4
  • David Ellioth Pulido-Ascencio
    • 1
  1. 1.National Institute of PerinatologyMexico CityMexico
  2. 2.National Institute of PsychiatryMexico CityMexico
  3. 3.National Institute of Genomic MedicineMexico CityMexico
  4. 4.Faculty of PsychologyAnahuac UniversityHuixquilucanMexico
  5. 5.National Council of Science and TechnologyMexico CityMexico

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