Inflammatory markers and treatment outcome in treatment resistant depression: A systematic review

Yang, Chenghao; Wardenaar, Klaas J.; Bosker, Fokko J.; Li, Jie; Schoevers, Robert A.

doi:10.1016/j.jad.2019.07.045

Cited by 107 publications

(76 citation statements)

References 62 publications

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“…A multitude of studies and meta-analyses show that patients with major depressive disorder (MDD) have, on average, increased serum levels of pro-inflammatory cytokines, like interleukin 1 beta (IL-1-beta), IL-6 and tumour necrosis factor alpha (TNF-alpha), and of the acute phase protein, C-reactive protein (CRP) 1,2,4,5 . Patients with 'treatment resistant depression' (TRD) are more likely to have increased inflammation 6,7 , as do patients with cardiovascular disorders, obesity, anxiety, and a history of childhood maltreatment 3,[8][9][10][11][12][13] .…”

Section: Introductionmentioning

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: Introductionmentioning

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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“…Importantly, elevated inflammation also is associated with treatment resistant depression (Yang et al, 2019). Although nascent, researchers have begun to explore whether specific depression treatment strategies that improve fatigue, such as behavioral activation, also lower inflammation (Euteneuer et al, 2017).…”

Section: Crp and Depression Criteriamentioning

confidence: 99%

“…Systemic low-grade inflammation is an established correlate of, and is gaining evidence as a potential causal risk factor for, depression symptoms (Dhabhar et al, 2009;Dowlati et al, 2010;Howren et al, 2009;Moriarity et al, 2020a). In fact, elevated inflammation is associated with treatment-resistant depression (Yang et al, 2019). In particular, the acute phase reactant Creactive protein (CRP) arguably is the most researched inflammatory index in depression research (Horn et al, 2018;Howren et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

How handling extreme C-reactive protein (CRP) values and regularization influences CRP and depression criteria associations in network analyses

Moriarity

Horn

Kautz

et al. 2021

Brain, Behavior, and Immunity

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Increasingly, it has been recognized that analysis at the symptom, rather than diagnostic, level will drive progress in the field of immunopsychiatry. Network analysis offers a useful tool in this pursuit with the ability to identify associations between immune markers and individual symptoms, independent of all other variables modeled. However, investigation into how methodological decisions (i.e., including vs. excluding participants with C-reactive protein (CRP) > 10 mg/L, regularized vs. nonregularized networks) influence results is necessary to establish best practices for the use of network analysis in immunopsychiatry. In a sample of 3,464 adult participants from the 2015-2016 National Health and Nutrition Examination Survey dataset, this study found consistent support for associations between CRP and fatigue and changes in appetite and some support for additional CRP-criterion associations. Methodologically, results consistently demonstrated that including individuals with CRP > 10 mg/L and estimating nonregularized networks provided better estimates of these associations. Thus, we recommend the use of nonregularized networks in immunopsychiatry and inclusion of cases with CRP values > 10 mg/L when testing the association between CRP and depression criteria in preliminary analyses, unless contraindicated by the research question being tested. Additionally, results most consistently suggest that CRP is uniquely related to fatigue and changes in appetite, supporting their inclusion in an immunometabolic phenotype of depression. Finally, these associations suggest that fatigue and changes in appetite might be particularly receptive to anti-inflammatory treatments. However, future research with more nuanced measures is necessary to parse out whether appetite increases or decreases drive this association. Further, longitudinal research is an important next step to test how these relationships manifest over time.

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“…Furthermore, increased levels of different genes and proteins related to innate immunity, such as interleukins 1β (IL-1β) and 6 (IL-6), tumor necrosis factor (TNF) and toll-like receptors 3 (TLR3) and 4 (TLR4), have been observed in the brain of patients with MDD [54,55]. Another peripheral inflammatory biomarker linked to depression, indicated by several studies, is the C reactive protein (CRP) [56,57]. Moreover, it has to be noted that the administration of inflammatory factors is able to "artificially" induce depressive symptoms in non-depressed individuals [58,59], while the pharmacological blockade of inflammatory processes has positive effects on depressive symptoms [60,61].…”

Section: Subsequent Hypotheses: the Neurodevelopmental Glutamatergicmentioning

confidence: 99%

Blues in the Brain and Beyond: Molecular Bases of Major Depressive Disorder and Relative Pharmacological and Non-Pharmacological Treatments

Maffioletti

Minelli

Tardito

et al. 2020

Genes

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Despite the extensive research conducted in recent decades, the molecular mechanisms underlying major depressive disorder (MDD) and relative evidence-based treatments remain unclear. Various hypotheses have been successively proposed, involving different biological systems. This narrative review aims to critically illustrate the main pathogenic hypotheses of MDD, ranging from the historical ones based on the monoaminergic and neurotrophic theories, through the subsequent neurodevelopmental, glutamatergic, GABAergic, inflammatory/immune and endocrine explanations, until the most recent evidence postulating a role for fatty acids and the gut microbiota. Moreover, the molecular effects of established both pharmacological and non-pharmacological approaches for MDD are also reviewed. Overall, the existing literature indicates that the molecular mechanisms described in the context of these different hypotheses, rather than representing alternative ones to each other, are likely to contribute together, often with reciprocal interactions, to the development of MDD and to the effectiveness of treatments, and points at the need for further research efforts in this field.

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Inflammatory markers and treatment outcome in treatment resistant depression: A systematic review

Cited by 107 publications

References 62 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

How handling extreme C-reactive protein (CRP) values and regularization influences CRP and depression criteria associations in network analyses

Blues in the Brain and Beyond: Molecular Bases of Major Depressive Disorder and Relative Pharmacological and Non-Pharmacological Treatments

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