Effects of SSRIs on peripheral inflammatory markers in patients with major depressive disorder: A systematic review and meta-analysis

Wang, Lina; Wang, Ruzhan; Liu, Lanfen; Qiao, Dan; Baldwin, David S.

doi:10.1016/j.bbi.2019.02.021

Cited by 132 publications

(80 citation statements)

References 83 publications

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“…Meta-analyses of longitudinal studies have shown that antidepressant treatment (on average, for 6-12 weeks) is associated with decreases in serum or plasma cytokines, such as IL-6 and TNF-alpha, both in general 40 and for SSRIs in particular 41 , with the most recent meta-analyses showing that TNF-alpha, but not IL-6, is differentially affected in responders only 42 . Data on longitudinal changes in mRNA expression are much more limited; for example, we published 15 that 8-weeks of antidepressants (escitalopram or nortriptyline) decrease IL-6 mRNA, but this is driven by responders only, while TNF-alpha mRNA levels do not change.…”

Section: Discussionmentioning

confidence: 99%

Whole-blood expression of inflammasome- and glucocorticoid-related mRNAs correctly separates treatment-resistant depressed patients from drug-free and responsive patients in the BIODEP study

et al. 2020

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The mRNA expression signatures associated with the ‘pro-inflammatory’ phenotype of depression, and the differential signatures associated with depression subtypes and the effects of antidepressants, are still unknown. We examined 130 depressed patients (58 treatment-resistant, 36 antidepressant-responsive and 36 currently untreated) and 40 healthy controls from the BIODEP study, and used whole-blood mRNA qPCR to measure the expression of 16 candidate mRNAs, some never measured before: interleukin (IL)-1-beta, IL-6, TNF-alpha, macrophage inhibiting factor (MIF), glucocorticoid receptor (GR), SGK1, FKBP5, the purinergic receptor P2RX7, CCL2, CXCL12, c-reactive protein (CRP), alpha-2-macroglobulin (A2M), acquaporin-4 (AQP4), ISG15, STAT1 and USP-18. All genes but AQP4, ISG15 and USP-18 were differentially regulated. Treatment-resistant and drug-free depressed patients had both increased inflammasome activation (higher P2RX7 and proinflammatory cytokines/chemokines mRNAs expression) and glucocorticoid resistance (lower GR and higher FKBP5 mRNAs expression), while responsive patients had an intermediate phenotype with, additionally, lower CXCL12. Most interestingly, using binomial logistics models we found that a signature of six mRNAs (P2RX7, IL-1-beta, IL-6, TNF-alpha, CXCL12 and GR) distinguished treatment-resistant from responsive patients, even after adjusting for other variables that were different between groups, such as a trait- and state-anxiety, history of childhood maltreatment and serum CRP. Future studies should replicate these findings in larger, longitudinal cohorts, and test whether this mRNA signature can identify patients that are more likely to respond to adjuvant strategies for treatment-resistant depression, including combinations with anti-inflammatory medications.

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Section: Discussionmentioning

confidence: 99%

Whole-blood expression of inflammasome- and glucocorticoid-related mRNAs correctly separates treatment-resistant depressed patients from drug-free and responsive patients in the BIODEP study

et al. 2020

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“…Lower IL-10 has been observed in depression, while IL-10 was elevated after antidepressant treatment (Dai et al, 2020;Lee et al, 2020). In contrast, studies have reported higher IL-10 in depressive patients and decreased IL-10 after treatment for depression (Köhler et al, 2018;Himmerich et al, 2019;Wang et al, 2019;Brunoni et al, 2020). One explanation for increased IL-10 is that it is an anti-inflammatory response to correct an inflammatory activation caused by higher levels of proinflammatory cytokines (Bhattacharya and Drevets, 2017).…”

Section: Discussionmentioning

confidence: 99%

Long-Term Exposure to Ceftriaxone Sodium Induces Alteration of Gut Microbiota Accompanied by Abnormal Behaviors in Mice

Zhao

Wang

et al. 2020

Front. Cell. Infect. Microbiol.

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Background: Growing evidence points out that a disturbance of gut microbiota may also disturb the gut-brain communication. However, it is not clear to what extent the alteration of microbiota composition can modulate brain function, affecting host behaviors. Here, we investigated the effects of gut microbiota depletion on emotional behaviors. Methods: Mice in the experimental group were orally administered ceftriaxone sodium solution (250 mg/ml, 0.2 ml/d) for 11 weeks. The open-field test and tail-suspension test were employed for the neurobehavioral assessment of the mice. Fecal samples were collected for 16s rDNA sequencing. The serum levels of cytokines and corticosterone were quantified using enzyme-linked immunosorbent assays. The immunohistochemistry method was used for the detection of brain-derived neurotrophic factor (BDNF) and c-Fos protein. Results: The gut microbiota for antibiotic-treated mice showed lower richness and diversity compared with normal controls. This effect was accompanied by increased anxiety-like, depression-like, and aggressive behaviors. We found these changes to be possibly associated with a dysregulation of the immune system, abnormal activity of the hypothalamic-pituitary-adrenal axis, and an alteration of neurochemistry. Conclusions: The findings demonstrate the indispensable role of microbiota in the gut-brain communication and suggest that the absence of conventional gut microbiota could affect the nervous system, influencing brain function.

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“…MDD is also heavily linked to systemic inflammatory responses through 5-HT (194,195,(203)(204)(205). SSRIs alleviate depressive symptoms by decreasing the myeloid cell production of pro-inflammatory cytokines, resisting mast cell activation, and reducing chronic inflammation (193)(194)(195)(196). MS patients with depression characterized with a high concentration of proinflammatory T H1 and T H17 cytokines are related to reduced synthesis and availability of 5-HT in the CNS (206).…”

Section: Discussionmentioning

confidence: 99%

“…It is well-accepted that many SERT blockers including the serotonin selective reuptake inhibitors (SSRI), which increase extracellular 5-HT concentration, have immunoinhibitory effects, such as reduced lymphocyte proliferation and decreased cytokine production by myeloid cells in both animals and humans (193)(194)(195)(196). In a meta-analysis study of 827 patients suffering with major depressive disorder (MDD), the pooled effect estimate using bias-corrected standardized mean difference indicates that SSRI treatment decreases serum levels of pro-inflammatory cytokines, IL-6, TNFα, and IL-1β, and anti-inflammatory cytokine IL-10 (194,(197)(198)(199). In a murine LPS-induced septic shock model, fluoxetine markedly decreased circulating levels of TNFα (200).…”

Section: Immunosuppressive Effectsmentioning

confidence: 99%

Critical Neurotransmitters in the Neuroimmune Network

et al. 2020

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Immune cells rely on cell-cell communication to specify and fine-tune their responses. They express an extensive network of cell communication modes, including a vast repertoire of cell surface and transmembrane receptors and ligands, membrane vesicles, junctions, ligand and voltage-gated ion channels, and transporters. During a crosstalk between the nervous system and the immune system these modes of cellular communication and the downstream signal transduction events are influenced by neurotransmitters present in the local tissue environments in an autocrine or paracrine fashion. Neurotransmitters thus influence innate and adaptive immune responses. In addition, immune cells send signals to the brain through cytokines, and are present in the brain to influence neural responses. Altered communication between the nervous and immune systems is emerging as a common feature in neurodegenerative and immunopathological diseases. Here, we present the mechanistic frameworks of immunostimulatory and immunosuppressive effects critical neurotransmitters-dopamine (3,4-dihydroxyphenethylamine), serotonin (5hydroxytryptamine), substance P (trifluoroacetate salt powder), and L-glutamateexert on lymphocytes and non-lymphoid immune cells. Furthermore, we discuss the possible roles neurotransmitter-driven neuroimmune networks play in the pathogenesis of neurodegenerative disorders, autoimmune diseases, cancer, and outline potential clinical implications of balancing neuroimmune crosstalk by therapeutic modulation.

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Effects of SSRIs on peripheral inflammatory markers in patients with major depressive disorder: A systematic review and meta-analysis

Cited by 132 publications

References 83 publications

Whole-blood expression of inflammasome- and glucocorticoid-related mRNAs correctly separates treatment-resistant depressed patients from drug-free and responsive patients in the BIODEP study

Whole-blood expression of inflammasome- and glucocorticoid-related mRNAs correctly separates treatment-resistant depressed patients from drug-free and responsive patients in the BIODEP study

Long-Term Exposure to Ceftriaxone Sodium Induces Alteration of Gut Microbiota Accompanied by Abnormal Behaviors in Mice

Critical Neurotransmitters in the Neuroimmune Network

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