Peripheral cytokine levels and response to antidepressant treatment in depression: a systematic review and meta-analysis

Liu, Jiajia; Wei, Yunbing; Strawbridge, Rebecca; Bao, Yanping; Chang, Suhua; Shi, Le; Que, Jian-Yu; Gadad, Bharathi S.; Trivedi, Madhukar H.; Kelsoe, John R.; Lü, Lin

doi:10.1038/s41380-019-0474-5

Cited by 269 publications

(186 citation statements)

References 69 publications

Supporting

Mentioning

148

Contrasting

Unclassified

Order By: Relevance

“…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

View full text Add to dashboard Cite

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.

show abstract

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

View full text Add to dashboard Cite

show abstract

“…30 Other meta-analyses have shown that traditional antidepressants (for example selective serotonin reuptake inhibitors (SSRIs) and serotonin-noradrenaline reuptake inhibitors) are associated with a reduction in IL-6, TNF-α and CCL-2 31 and that persistently elevated TNF-α is associated with treatment resistance. 32,33 Retrospective cohort studies indicate that inflammation may play a role in the onset of mood symptoms and that elevated peripheral inflammatory markers in early life are predictive of adult depressive symptomology. 34,35 Within the literature, there is significant heterogeneity between studies and in particular, there are substantial differences in how comorbidities are controlled for.…”

Section: Resultsmentioning

confidence: 99%

Inflammation as a treatment target in mood disorders: review

et al. 2020

Self Cite

View full text Add to dashboard Cite

Background Mood disorders, i.e. major depressive disorder (MDD) and bipolar disorders, are leading sources of disability worldwide. Currently available treatments do not yield remission in approximately a third of patients with a mood disorder. This is in part because these treatments do not target a specific core pathology underlying these heterogeneous disorders. In recent years, abnormal inflammatory processes have been identified as putative pathophysiological mechanisms and treatment targets in mood disorders, particularly among individuals with treatment-resistant conditions. Aims In this selective review, we aimed to summarise recent advances in the field of immunopsychiatry, including emerging pathophysiological models and findings from treatment ttrials of immunomodulatory agents for both MDD and bipolar disorders. Method We performed a literature review by searching Medline for clinical trials of immunomodulating agents as monotherapy or adjunctive treatments in MDD and bipolar disorders. Included studies are randomised controlled trials (RCTs), cluster RCTs or cross-over trials of immunomodulating agents that had an active comparator or a placebo-arm. Results Current evidence shows an association between inflammation and mood symptoms. However, there is conflicting evidence on whether this link is causal. Conclusions Future studies should focus on identifying specific neurobiological underpinnings for the putative causal association between an activated inflammatory response and mood disorders. Results of these studies are needed before further treatment trials of immunomodulatory agents can be justified.

show abstract

“…Further clinical research is essential to clearly identify biomarkers for the assessment of inflammation-vascular-autonomic dysfunction, which could be used for personalized prevention and treatment of CVD in depressive patients. Currently, increasing attention is focused on the efficacy of anti-inflammatory treatment in major depressive disorder [84,85]; thus, the development of novel therapeutic interventions targeting the immune, vascular, and autonomic nervous systems in MDD is of particular importance.…”

Section: Concluding Remarks and Perspectivesmentioning

confidence: 99%

Novel Insight into Neuroimmune Regulatory Mechanisms and Biomarkers Linking Major Depression and Vascular Diseases: The Dilemma Continues

Tonhajzerová

Sekaninova

Olexova

et al. 2020

IJMS

View full text Add to dashboard Cite

Major depressive disorder (MDD) represents a serious health problem estimated to affect 350 million people globally. Importantly, MDD has repeatedly emerged as an etiological or prognostic factor in cardiovascular disease (CVD) development, including vascular pathology. Several linking pathomechanisms between MDD and CVD involve abnormal autonomic regulation, inflammation, and endothelial dysfunction as an early preclinical stage of atherosclerosis. However, the cause of accelerated atherosclerosis in MDD patients remains unclear. Recently, the causal relationships between MDD and mediator (e.g., inflammation and/or endothelial dysfunction), as well as the causal pathways from the mediator to atherosclerosis, were discussed. Specifically, MDD is accompanied by immune dysregulation, resulting in increased production of proinflammatory cytokines (e.g., interleukin (IL)-6 and tumor necrosis factor (TNF)-α), which could lead to depression-linked abnormalities in brain function. Further, MDD has an adverse effect on endothelial function; for example, circulating markers of endothelial dysfunction (e.g., soluble adhesion molecules, von Willebrand factor) have been linked with depression. Additionally, MDD-linked autonomic dysregulation, which is characterized by disrupted sympathovagal balance associated with excessive circulating catecholamines, can contribute to CVD. Taken together, activated inflammatory response, endothelial dysfunction, and autonomic dysregulation could affect gradual atherosclerosis progression, resulting in a higher risk of developing CVD in MDD. This review focused on the pathomechanisms linking MDD and CVD with respect to neuroimmune regulation, and the description of promising biomarkers, which is important for the early diagnosis and personalized prevention of CVD in major depression.

show abstract

Peripheral cytokine levels and response to antidepressant treatment in depression: a systematic review and meta-analysis

Cited by 269 publications

References 69 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

Inflammation as a treatment target in mood disorders: review

Novel Insight into Neuroimmune Regulatory Mechanisms and Biomarkers Linking Major Depression and Vascular Diseases: The Dilemma Continues

Contact Info

Product

Resources

About