Effect of immune activation on the kynurenine pathway and depression symptoms – A systematic review and meta-analysis

Hunt, Charlotte; Cordeiro, Thiago Macedo e; Suchting, Robert; Dios, Constanza de; Leal, Valeria A. Cuellar; Soares, Jair C.; Dantzer, Robert; Teixeira, Antônio Lúcio; Selvaraj, Sudhakar

doi:10.1016/j.neubiorev.2020.08.010

Cited by 93 publications

(60 citation statements)

References 60 publications

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“…Previous research (Thomas et al, 2020) has found a correlation between increases of interleukin 6 and kynurenine levels in COVID-19 patients compared to controls. Finally, kynurenine pathway upregulation as part of an inflammatory response is known to impact serotonin levels negatively (Hunt et al, 2020;Li et al, 2017), as also observed in our results. Interestingly we observed nicotinamide (MSI 1) levels to be 1.5-fold higher in severe case, but not significant in outcome.…”

Section: Elevated Serum Cytosine Association With Severity and Outcomesupporting

confidence: 89%

Untargeted metabolomics of COVID-19 patient serum reveals potential prognostic markers of both severity and outcome

Roberts

Muelas

Taylor

et al. 2020

Preprint

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The diagnosis of COVID-19 is normally based on the qualitative detection of viral nucleic acid sequences. Properties of the host response are not measured but are key in determining outcome. Although metabolic profiles are well suited to capture host state, existing metabolomics studies are either underpowered, measure only a restricted subset of metabolites (‘targeted metabolomics’), compare infected individuals against uninfected control cohorts that are not suitably matched, or do not provide a compact predictive model.We here provide a well-powered, untargeted metabolomics assessment of 120 COVID-19 patient samples acquired at hospital admission. The study aims to predict patient’s infection severity (i.e. mild or severe) and potential outcome (i.e. discharged or deceased).High resolution untargeted LC-MS/MS analysis was performed on patient serum using both positive and negative ionization. A subset of 20 intermediary metabolites predictive of severity or outcome were selected based on univariate statistical significance and a multiple predictor Bayesian logistic regression model. The predictors were selected for their relevant biological function and include cytosine (reflecting viral load), kynurenine (reflecting host inflammatory response), nicotinuric acid, and multiple short chain acylcarnitines (energy metabolism) among others.Currently, this approach predicts outcome and severity with a Monte Carlo cross validated area under the ROC curve of 0.792 (SD 0.09) and 0.793 (SD 0.08), respectively. Prognostic tests based on the markers discussed in this paper could allow improvement in the planning of COVID-19 patient treatment.

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Section: Elevated Serum Cytosine Association With Severity and Outcomesupporting

confidence: 89%

Untargeted metabolomics of COVID-19 patient serum reveals potential prognostic markers of both severity and outcome

Roberts

Muelas

Taylor

et al. 2020

Preprint

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“…This is consistent with the leaky-gut hypothesis, which narrates the vicious cycle of interaction between the gut microbiota, CNS and the periphery in the activation of inflammatory responses [103,[105][106][107]. One of the proposed mechanisms in which proinflammatory cytokines induce depressive symptoms is through the activation of the indoleamine 2,3dioxygenase (IDO) enzyme that facilitates the metabolic breakdown of tryptophan (TRP) into kynurenine (KYN) [108]. Elevated plasma KYN and the KYN/TRP ratio have been positively correlated with the severity of depressive symptoms.…”

Section: Inflammationsupporting

confidence: 84%

Exploring the Role and Potential of Probiotics in the Field of Mental Health: Major Depressive Disorder

et al. 2021

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The field of probiotic has been exponentially expanding over the recent decades with a more therapeutic-centered research. Probiotics mediated microbiota modulation within the microbiota–gut–brain axis (MGBA) have been proven to be beneficial in various health domains through pre-clinical and clinical studies. In the context of mental health, although probiotic research is still in its infancy stage, the promising role and potential of probiotics in various mental disorders demonstrated via in-vivo and in-vitro studies have laid a strong foundation for translating preclinical models to humans. The exploration of the therapeutic role and potential of probiotics in major depressive disorder (MDD) is an extremely noteworthy field of research. The possible etio-pathological mechanisms of depression involving inflammation, neurotransmitters, the hypothalamic–pituitary–adrenal (HPA) axis and epigenetic mechanisms potentially benefit from probiotic intervention. Probiotics, both as an adjunct to antidepressants or a stand-alone intervention, have a beneficial role and potential in mitigating anti-depressive effects, and confers some advantages compared to conventional treatments of depression using anti-depressants.

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“…Here we describe the KP and review some of the current knowledge of its involvement in the pathophysiology of inflammatory depression [50]. The kynurenine pathway (KP) involves a series of enzymatic steps in the metabolism of essential amino acid tryptophan and has been extensively studied in relation to both inflammation and depression [51][52][53]. In particular, focus has been placed on how proinflammatory cytokines (e.g., TNF-α) may activate the enzyme indoleamine 2,3-dioxygenase (IDO), which converts tryptophan to kynurenine in the first and rate-limiting step of the KP [54,55].…”

Section: Mechanisms Of "Inflammatory Depression"mentioning

confidence: 99%

Inflammatory Depression—Mechanisms and Non-Pharmacological Interventions

Suneson

Lindahl

Hårsmar

et al. 2021

IJMS

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Treatment of depression is hampered by the failure to identify distinct symptom profiles with distinct pathophysiologies that differentially respond to distinct treatments. We posit that inflammatory depression is a meaningful depression subtype associated with specific symptoms and biological abnormalities. We review several upstream, potentially causative, mechanisms driving low-grade inflammation in this subtype of depression. We also discuss downstream mechanisms mediating the link between inflammation and symptoms of depression, including alterations in dopaminergic neurotransmission and tryptophan metabolism. Finally, we review evidence for several non-pharmacological interventions for inflammatory depression, including probiotics, omega-3 fatty acids, and physical exercise interventions. While some evidence suggests that these interventions may be efficacious in inflammatory depression, future clinical trials should consider enriching patient populations for inflammatory markers, or stratify patients by inflammatory status, to confirm or refute this hypothesis.

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Effect of immune activation on the kynurenine pathway and depression symptoms – A systematic review and meta-analysis

Cited by 93 publications

References 60 publications

Untargeted metabolomics of COVID-19 patient serum reveals potential prognostic markers of both severity and outcome

Untargeted metabolomics of COVID-19 patient serum reveals potential prognostic markers of both severity and outcome

Exploring the Role and Potential of Probiotics in the Field of Mental Health: Major Depressive Disorder

Inflammatory Depression—Mechanisms and Non-Pharmacological Interventions

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