The acute‐phase mediator serum amyloid A is associated with symptoms of depression and fatigue

Bryleva, Elena Y.; Keaton, Sarah A.; Grit, Jamie; Madaj, Zach; Sauro-Nagendra, A.; Smart, LeAnn; Halstead, Scott B.; Achtyes, Eric D.; Brundin, Lena

doi:10.1111/acps.12730

Cited by 20 publications

(18 citation statements)

References 52 publications

(53 reference statements)

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“…Accordingly, activation of SNS by stress or different drugs could target immune cells (e.g., macrophages) that express all types of ARs. The present findings are in line with those of previous studies indicating the up-regulating effect of stress on SAA (Bryleva et al 2017; Collier et al 2011; Turlo et al 2015). They further support the involvement of different ARs in the stress-driven synthesis of both SAA1/2 and SAA3 in the liver, while total serum SAA protein load was also increased, indicating an AR-mediated systemic increase of these acute phase proteins.…”

Section: Discussionsupporting

confidence: 94%

Adrenoceptor-stimulated inflammatory response in stress-induced serum amyloid A synthesis

et al. 2019

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Rationale Stressful life events are suggested to contribute to the development of various pathologies, such as cardiovascular disorders, whose etiopathogenesis is highly associated with elevated levels of serum amyloid A (SAA) proteins. SAA synthesis in the liver is regulated by a complex network of cytokines acting independently or in concert with various hormones/stimulants including the stress-activated sympathetic nervous system. Objective This study aims to investigate the underlying mechanisms that regulate the stress-induced hepatic synthesis of SAA, with particular focus on adrenoceptors (AR), major components of the sympathoadrenal response to stress. Methods and results We demonstrated that repeated stress elevates IL-1β, IL-6, and TNFα serum levels in mice, accompanied by increased synthesis and secretion of hepatic SAA1/2 and SAA3, an effect that was blocked by AR antagonists. Moreover, stimulation of α1 - and β1/2-ARs mimics the stress effect on SAA1/2 regulation, whereas α2-AR stimulation exhibits a relatively weak impact on SAA. In support of the essential cytokine contribution in the AR-agonist induced SAA production is the fact that the anti-inflammatory drug, sodium salicylate, prevented the AR-stimulated hepatic SAA1/2 synthesis by reducing IL-1β levels, whereas IL-1β inhibition with Anakinra mimics this sodium salicylate preventive effect, thus indicating a crucial role for IL-1β. Interestingly, the AR-driven SAA3 synthesis was elevated by sodium salicylate in a TNFα-dependent way, supporting diverse and complex regulatory roles of cytokines in SAA production. In contrast to α1/α2-AR, the β1/2-AR-mediated SAA1/2 and SAA3 upregulation cannot be reversed by fenofibrate, a hypolipidemic drug with anti-inflammatory properties. Conclusion Taken together, these findings strongly support a critical role of the AR-stimulated inflammatory response in the hepatic SAA production under stressful conditions, highlighting distinct AR type-specific mechanisms that regulate the hepatic synthesis of SAA1/2 and SAA3.

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Section: Discussionsupporting

confidence: 94%

Adrenoceptor-stimulated inflammatory response in stress-induced serum amyloid A synthesis

et al. 2019

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“…Elevated levels of IL-10 are often reported in people with MDD [78][79][80]. Some researchers also observed that MDD severity is related to increased IL-10 [81,82].…”

Section: Il-10mentioning

confidence: 99%

Biomarkers of Post-COVID Depression

Lorkiewicz

Waszkiewicz

2021

JCM

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The COVID-19 pandemic is spreading around the world and 187 million people have already been affected. One of its after-effects is post-COVID depression, which, according to the latest data, affects up to 40% of people who have had SARS-CoV-2 infection. A very important issue for the mental health of the general population is to look for the causes of this complication and its biomarkers. This will help in faster diagnosis and effective treatment of the affected patients. In our work, we focused on the search for major depressive disorder (MDD) biomarkers, which are also present in COVID-19 patients and may influence the development of post-COVID depression. For this purpose, we searched PubMed, Scopus and Google Scholar scientific literature databases using keywords such as ‘COVID-19’, ‘SARS-CoV-2’, ‘depression’, ‘post-COVID’, ‘biomarkers’ and others. Among the biomarkers found, the most important that were frequently described are increased levels of interleukin 6 (IL-6), soluble interleukin 6 receptor (sIL-6R), interleukin 1 β (IL-1β), tumor necrosis factor α (TNF-α), interferon gamma (IFN-γ), interleukin 10 (IL-10), interleukin 2 (IL-2), soluble interleukin 2 receptor (sIL-2R), C-reactive protein (CRP), Monocyte Chemoattractant Protein-1 (MCP-1), serum amyloid a (SAA1) and metabolites of the kynurenine pathway, as well as decreased brain derived neurotrophic factor (BDNF) and tryptophan (TRP). The biomarkers identified by us indicate the etiopathogenesis of post-COVID depression analogous to the leading inflammatory hypothesis of MDD.

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“…In fact, it has been postulated that peripheral inflammation may not always result in either neuroinflammation or major depression. In unselected groups of depressed patients, levels of inflammatory biomarkers either do not correlate or correlate modestly with depression severity ( Cassidy-Bushrow et al, 2012 ; Bryleva et al, 2017 ; Jha et al, 2017b ; Köhler-Forsberg et al, 2017 ). Thus, identifying peripheral markers in blood that reflect neuroinflammation may help with developing novel treatments and could also identify specific subgroups that would require different treatments, thus personalizing the choice of currently available antidepressants.…”

Section: Introductionmentioning

confidence: 96%

Platelet-Derived Growth Factor as an Antidepressant Treatment Selection Biomarker: Higher Levels Selectively Predict Better Outcomes with Bupropion-SSRI Combination

Jha

Minhajuddin

Gadad

2017

International Journal of Neuropsychopharmacology

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BackgroundPlatelet derived growth factor is integral to maintenance of blood brain barrier, increases in response to blood brain barrier disruption, and may reflect neuroinflammation. Based on previous reports of better outcomes with dopaminergic antidepressants in depressed patients with elevated inflammatory biomarkers, we hypothesize that elevated peripheral platelet derived growth factor levels can serve as a powerful biomarker for selecting dopaminergic antidepressants.MethodsPlatelet derived growth factor, basic fibroblast growth factor, and granulocyte colony stimulating factor were measured as part of Bioplex Pro human cytokine 27-plex kit in participants of the Combining Medications to Enhance Depression Outcomes trial who provided baseline plasma (n=166) and were treated with either bupropion-plus-escitalopram, escitalopram-plus-placebo, or venlafaxine-plus-mirtazapine. Differential changes in overall symptom severity and anhedonia as well as side effects were tested with a treatment-arm-by-biomarker interaction in mixed model analyses. Effect of biomarkers with significant interaction was calculated in subsequent analyses stratified by treatment arm.ResultsThere was a significant treatment-arm-by-platelet derived growth factor interaction for depression severity (P=.03) and anhedonia (P=.008) but not for side effects (P=.44). Higher baseline platelet derived growth factor level was associated with greater reduction in depression severity (effect size=0.71, P=.015) and anhedonia (effect size=0.66, P=.02) in the bupropion- selective serotonin reuptake inhibitor but not the other two treatment arms. There was no significant treatment-arm-by-biomarker interaction for both depression severity and side effects with the other two biomarkers.ConclusionAs compared with selective serotonin reuptake inhibitor monotherapy or venlafaxine-plus-mirtazapine, bupropion-plus-escitalopram selectively improves anhedonia, which in turn results in improved overall depression severity in depressed patients with elevated platelet derived growth factor levels.

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The acute‐phase mediator serum amyloid A is associated with symptoms of depression and fatigue

Cited by 20 publications

References 52 publications

Adrenoceptor-stimulated inflammatory response in stress-induced serum amyloid A synthesis

Adrenoceptor-stimulated inflammatory response in stress-induced serum amyloid A synthesis

Biomarkers of Post-COVID Depression

Platelet-Derived Growth Factor as an Antidepressant Treatment Selection Biomarker: Higher Levels Selectively Predict Better Outcomes with Bupropion-SSRI Combination

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