Abstract
Several lines of evidence have strongly implicated inflammatory processes in the pathobiology of major depressive disorder (MDD). However, the cellular origin of inflammatory signals and their specificity remain unclear. We examined the phenotype and glucocorticoid signaling in key cell populations of the innate immune system (monocytes) vs. adaptive immunity (T cells) in a sample of 35 well-characterized, antidepressant-free patients with MDD and 35 healthy controls individually matched for age, sex, smoking status and body mass index. Monocyte and T cell phenotype was assessed by flow cytometry. Cell-specific steroid signaling was determined by mRNA expression of pre-receptor regulation (11β-hydroxysteroid dehydrogenase type 1; 11β -HSD1), steroid receptor expression [glucocorticoid receptor (GR) and mineralocorticoid receptor (MR)], and the downstream target glucocorticoid-induced leucine-zipper (GILZ). We also collected salivary cortisol samples (8:00 a.m. and 10:00 p.m.) on two consecutive days. Patients showed a shift toward a pro-inflammatory phenotype characterized by higher frequency and higher absolute numbers of non-classical monocytes. No group differences were observed in major T cell subset frequencies and phenotype. Correspondingly, gene expression indicative of steroid resistance (i.e., lower expression of GR and GILZ) in patients with MDD was specific to monocytes and not observed in T cells. Monocyte phenotype and steroid receptor expression was not related to cortisol levels or serum levels of IL-6, IL-1β, or TNF-α. Our results thus suggest that in MDD, cells of the innate and adaptive immune system are differentially affected with shifts in monocyte subsets and lower expression of steroid signaling related genes.
Highlights
Several independent lines of evidence have implicated the immune system in the pathobiology of mood disorders, major depressive disorder (MDD) [1,2,3]
Patients with MDD showed a shift toward non-classical monocytes with no group differences in major T cell subset frequencies and phenotype, B cells or NK cells
Expression of key steroid-signaling genes glucocorticoid receptor (GR) and glucocorticoid-induced leucine-zipper (GILZ) was lower in monocytes obtained from MDD patients with no group differences observed in T cells
Summary
Several independent lines of evidence have implicated the immune system in the pathobiology of mood disorders, major depressive disorder (MDD) [1,2,3]. Numerous studies and several meta-analyses have demonstrated higher levels of circulating cytokines, such as interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α), in MDD [4, 5]. Serum levels of cytokines reveal little about the specific cause of immune dysfunction and the cellular source of inflammation in MDD remains poorly understood. It is becoming increasingly clear that MDD is not a state of general immune activation but that innate and adaptive immune responses might be differentially affected [6]. Considerable evidence points toward activation of monocytes in MDD [7, 8]. Recent studies have suggested that adaptive immunity, T cell function, might be impaired in MDD [9,10,11]
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