The role of inflammation in depression: from evolutionary imperative to modern treatment target

Miller, Andrew H.; Raison, Charles L.

doi:10.1038/nri.2015.5

Cited by 2,704 publications

(2,102 citation statements)

References 130 publications

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“…There is already some evidence that anti‐inflammatory drugs can have antidepressant efficacy 32. Our results are compatible with the mechanistic interpretation that this may be at least partly attributable to the effects of anti‐inflammatory drugs on “normalization” of an inflammation‐induced bias in tryptophan and kynurenine metabolism.…”

Section: Discussionsupporting

confidence: 89%

“…The anti‐inflammatory activity of COX inhibitors is thought to depend on preventing inducible prostaglandin production, which can also act in an autocrine manner in macrophages through inducible prostaglandin receptors 25. Both COX‐inhibiting and TNFα‐inhibiting drugs have been shown to have some antidepressant and anxiolytic effects in patients with psychologic symptoms in the context of medical inflammatory disorders 32. Synthetic glucocorticoids, such as prednisolone, are amongst the most commonly prescribed anti‐inflammatory agents, and act by inducing multiple feedback repressors of inflammation, including IκB and DUSP1 33.…”

Section: Introductionmentioning

confidence: 99%

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Effects of anti-inflammatory drugs on the expression of tryptophan-metabolism genes by human macrophages

Regan

Gill

Clohisey

et al. 2018

Journal of Leukocyte Biology

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Several lines of evidence link macrophage activation and inflammation with (monoaminergic) nervous systems in the etiology of depression. IFN treatment is associated with depressive symptoms, whereas anti‐TNFα therapies elicit positive mood. This study describes the actions of 2 monoaminergic antidepressants (escitalopram, nortriptyline) and 3 anti‐inflammatory drugs (indomethacin, prednisolone, and anti‐TNFα antibody) on the response of human monocyte‐derived macrophages (MDMs) from 6 individuals to LPS or IFN‐α. Expression profiling revealed robust changes in the MDM transcriptome (3294 genes at P < 0.001) following LPS challenge, whereas a more limited subset of genes (499) responded to IFNα. Contrary to published reports, administered at nontoxic doses, neither monoaminergic antidepressant significantly modulated the transcriptional response to either inflammatory challenge. Each anti‐inflammatory drug had a distinct impact on the expression of inflammatory cytokines and on the profile of inducible gene expression—notably on the regulation of enzymes involved in metabolism of tryptophan. Inter alia, the effect of anti‐TNFα antibody confirmed a predicted autocrine stimulatory loop in human macrophages. The transcriptional changes were predictive of tryptophan availability and kynurenine synthesis, as analyzed by targeted metabolomic studies on cellular supernatants. We suggest that inflammatory processes in the brain or periphery could impact on depression by altering the availability of tryptophan for serotonin synthesis and/or by increasing production of neurotoxic kynurenine.

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Effects of anti-inflammatory drugs on the expression of tryptophan-metabolism genes by human macrophages

Regan

Gill

Clohisey

et al. 2018

Journal of Leukocyte Biology

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“…Recently, it has been reported that psychological and/or acute intense stressor exposure in the absence of overt tissue damage can evoke a detectable local and systemic sterile inflammatory response and that DAMPs may have a (Fleshner, 2013;Frank et al, 2015b;Maslanik et al, 2013;Miller et al, 2015).…”

Section: Stress Damps and Sterile Inflammationmentioning

confidence: 99%

“…Specifically, patients with depression had increased expression of NLRP3 and caspase-1 in peripheral blood mononuclear cells (Alcocer-Gomez et al (2014b)). Thus, sterile inflammation mediated by DAMPs and the inflammasome and evoked after exposure to psychological stressors may have a role in the pathogenesis of MDDs and other psychopathologies (Alcocer-Gomez and Cordero, 2014a; Kessler, 1997;Miller et al, 2015).…”

Section: Stress Damps and Sterile Inflammationmentioning

confidence: 99%

“…Inflammatory states in the body and/or central nervous system (CNS) impact a variety of brain functions including mood (Miller and Raison, 2015). There is strong evidence that patients with major depressive disorder (MDD), for example, have elevated levels of inflammatory proteins in the blood, and many inflammatory diseases are associated with increased rates of MDD (Howren et al, 2009;Schiepers et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

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Danger Signals and Inflammasomes: Stress-Evoked Sterile Inflammation in Mood Disorders

Fleshner

Frank

Maier

2016

Neuropsychopharmacol

183

125

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Major depressive disorder (MDD) and other mood disorders remain difficult to effectively treat, and innovative interventions and therapeutic targets are needed. Psychological stressors and inappropriate inflammation increase the risk and severity of mood disorders; however, only recently have the importance of sterile inflammatory processes in this effect been revealed. This review will introduce the reader to pathogen vs sterile inflammation, inflammatory receptor-ligand interactions, microbialassociated molecular patterns (MAMPs), pathogen-associated molecular patterns (PAMPs), danger-associated molecular patterns (DAMPs), and the more recent discovery of the role of the inflammasome in peripheral and central nervous system cytokine/chemokine inflammatory responses. The review will focus on current preclinical and clinical evidence that sterile inflammation and inflammasome-dependent signaling may contribute to mood disorders. By understanding these inflammatory signaling processes, new approaches for quieting chronic or inappropriate inflammatory states may be revealed and this could serve as novel pharmacological targets for the treatment of mood disorders.

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Depression and Anxiety in Adults With Hidradenitis Suppurativa

et al. 2019

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IMPORTANCE Previous studies suggest that depression and anxiety are common in patients with hidradenitis suppurativa (HS), more so than other dermatological conditions. Yet, to the authors' knowledge, no previous systematic review or meta-analysis has estimated the prevalence or odds ratio (OR) for those psychiatric comorbidities in this population. OBJECTIVE To assess the prevalence and odds for depression and anxiety in patients with HS. DATA SOURCES From July 25 to September 30, 2018, observational studies investigating the prevalence and odds for depression and anxiety in adults with HS were systematically searched without language restriction from the inception of each database to July 25, 2018, in PubMed/MEDLINE, Embase, and PsycINFO databases. Searches used various configurations of the terms hidradenitis suppurativa; acne inversa; depressive disorder; depression; anxiety; anxiety disorders; phobia, social; suicide; and suicide, attempted. In addition, the reference lists of included references were screened manually. STUDY SELECTION Two investigators independently screened references that measured prevalence rates and odds for depressive and anxiety symptoms in patients with HS. Of 136 unique references, 10 ultimately met inclusion criteria. DATA EXTRACTION AND SYNTHESIS Relevant data were extracted from eligible references. Authors were contacted to provide further information when necessary. Methodological quality of included studies was assessed through a modified version of the Newcastle-Ottawa Scale. Random-effects models were used to synthesize available evidence. MAIN OUTCOMES AND MEASURES Prevalence rates and ORs for depression and anxiety in adults with HS were the primary outcome measures. Heterogeneity across studies was assessed with the I 2 statistic. Sources of heterogeneity were explored through subgroup and meta-regression analyses. RESULTS Ten studies comprising 40 307 participants with HS met inclusion criteria. The overall prevalence of depression was 16.9% (95% CI, 9.9%-27.2%). Heterogeneity was large. In the subgroup of studies that considered a clinical criteria-based diagnosis of depression, the prevalence of depression was 11.9% (95% CI, 4.9%-26.2%), compared with 26.8% (95% CI, 20.4%-34.5%) in studies that used a screening instrument. The methodological quality of included studies moderated those findings. The OR for depression in individuals with HS compared with individuals without HS was 1.84 (95% CI, 1.57-2.15). The prevalence of anxiety was 4.9% (95% CI, 1.7%-13.2%); there were insufficient data to determine an odds ratio for anxiety in persons with HS because 2 studies included a comparison group. CONCLUSIONS AND RELEVANCE This systematic review and meta-analysis indicates that depression and anxiety are common comorbid conditions in patients with HS. Results suggest that the development of strategies to recognize and treat those psychiatric comorbidities in patients with HS is warranted.

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The role of inflammation in depression: from evolutionary imperative to modern treatment target

Cited by 2,704 publications

References 130 publications

Effects of anti-inflammatory drugs on the expression of tryptophan-metabolism genes by human macrophages

Effects of anti-inflammatory drugs on the expression of tryptophan-metabolism genes by human macrophages

Danger Signals and Inflammasomes: Stress-Evoked Sterile Inflammation in Mood Disorders

Depression and Anxiety in Adults With Hidradenitis Suppurativa

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