title: The Immune System and the Role of Inflammation in Perinatal Depression.
abstract: 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.
authors.affiliation: National Institute of Perinatology, Mexico City, Mexico. pleff@ymail.com.
authors.forename: Philippe
authors.initials: P
authors.lastname: Leff-Gelman
authors.affiliation: National Institute of Perinatology, Mexico City, Mexico.
authors.forename: Ismael
authors.initials: I
authors.lastname: Mancilla-Herrera
authors.affiliation: National Institute of Psychiatry, Mexico City, Mexico.|National Council of Science and Technology, Mexico City, Mexico.
authors.forename: Mónica
authors.initials: M
authors.lastname: Flores-Ramos
authors.affiliation: National Institute of Psychiatry, Mexico City, Mexico.
authors.forename: Carlos
authors.initials: C
authors.lastname: Cruz-Fuentes
authors.affiliation: National Institute of Genomic Medicine, Mexico City, Mexico.
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Reyes-Grajeda
authors.affiliation: Faculty of Psychology, Anahuac University, Huixquilucan, Mexico.
authors.forename: María Del Pilar
authors.initials: Mdel P
authors.lastname: García-Cuétara
authors.affiliation: Faculty of Psychology, Anahuac University, Huixquilucan, Mexico.
authors.forename: Marielle Danitza
authors.initials: MD
authors.lastname: Bugnot-Pérez
authors.affiliation: National Institute of Perinatology, Mexico City, Mexico.
authors.forename: David Ellioth
authors.initials: DE
authors.lastname: Pulido-Ascencio
mesh_terms: D003865:Major Depressive Disorder / Q000150:complications* / Q000276:immunology*; D005260:Female; D006801:Humans; D007107:Immune System / Q000503:physiopathology*; D007249:Inflammation / Q000209:etiology*; D011247:Pregnancy / Q000276:immunology; D012727:Sex Characteristics
keywords: Brain; Cytokine; Depression; Glucocorticoid; Immune system; Indoleamine 2,3 dioxygenase; Inflammation; Placenta; Pregnancy; Serotonin