Antidepressants normalize elevated Toll-like receptor profile in major depressive disorder

Hung, Yi-Yung; Huang, Kuan-Gen; Kang, Hong-Yo; Huang, Gloria Ya-Ling; Huang, Tiao‐Lai

doi:10.1007/s00213-015-4087-7

Cited by 78 publications

(70 citation statements)

References 48 publications

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“…The labeled fraction containing CD14 + monocytes was immediately stored at 80°C for further analysis. The protocol and primers used for mRNA analyses were the same as those used in our previous studies [19, 24]. …”

Section: Methodsmentioning

confidence: 99%

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Antidepressants Improve Negative Regulation of Toll-Like Receptor Signaling in Monocytes from Patients with Major Depression

Hung¹

2018

Neuroimmunomodulation

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Objective: Changes in the brain’s inflammatory status can lead to psychopathological responses, especially depression. Using animal models, recent studies have revealed that this pathology is due, in part, to innate immune responses of monocytes. Methods: We focus on the involvement of Toll-like receptors (TLRs) and expression of genes encoding their negative regulators, SOCS1, TOLLIP, SIGIRR, MyD88s, NOD2, and TNFAIP3, in CD14⁺ monocytes from 34 patients with major depressive disorder (MDD) and 33 healthy controls before and after treatment with antidepressants. We also seek to investigate their association with depression severity, measured by the 17-item Hamilton Depression Rating Scale (HAMD-17). Results: mRNA expression of all TLRs, except TLR3 and -5, was significantly higher in monocytes from patients with MDD than in those from controls. Conversely, the “brakes” in TLR signaling, including TOLLIP, MyD88s, NOD2, and TNFAIP3, were downregulated. In clinical findings, the remission group showed higher baseline TLR4 and lower baseline IRAK3 mRNA levels but only baseline elevated SOCS1 mRNA levels, which were inversely correlated with HAMD-17 scores, predicting worsened outcome in MDD patients. In addition, TNFAIP3 mRNA levels were increased by antidepressant treatment. Conclusion: Collectively, our findings suggest a role for dysregulation of TLR signaling in monocytes in MDD and identify a balancing effect of antidepressants on this dysregulation.

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Section: Methodsmentioning

confidence: 99%

“…Recent studies reported a significant association between TLR expression and mood disorder [19-21]. Postmodern study has shown that the protein and mRNA expression of TLRs are increased in the prefrontal cortex of adult depressed suicide victims [22].…”

Section: Introductionmentioning

confidence: 99%

Antidepressants Improve Negative Regulation of Toll-Like Receptor Signaling in Monocytes from Patients with Major Depression

Hung¹

2018

Neuroimmunomodulation

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“…17-5442-02; GE) density gradient centrifugation and stored at –80°C. The protocols for RNA preparation, cDNA synthesis, and mRNA analysis have been described [16]. Real-time quantitative reverse transcriptase PCR was performed using primers for human TNFAIP3 (forward, 5′-GGA CTT TGC GAA AGG ATC G-3′; reverse, 5′-TCA CAG CTT TCC GCA TAT TG-3′).…”

Section: Methodsmentioning

confidence: 99%

TNFAIP3 mRNA Level Is Associated with Psychological Anxiety in Major Depressive Disorder

Chen

Huang

et al. 2017

Neuroimmunomodulation

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Background: Major depressive disorder has been shown to be associated with inflammation and the dysregulation of innate immune responses. Previously, we showed an inverse correlation between the severity of depression and level of TNFAIP3 mRNA expression. The present study further evaluated the association between TNFAIP3 mRNA expression level and symptoms of major depressive disorder (MDD) in 91 patients (20 men and 71 women). Methods: The relationships between subscores on the 17-item Hamilton Depression Rating Scale (HAMD-17) and TNFAIP3 mRNA levels were assessed by multiple linear regression. Results: Only psychological anxiety on the HAMD-17 correlated significantly with TNFAIP3 mRNA expression. Other symptoms, such as depressed mood, insomnia, work and activities, and suicide, were not associated with TNFAIP3 mRNA expression. Conclusion: These findings suggest a significant association between anxiety and TNFAIP3 mRNA levels in patients with MDD.

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“…In rodents, a recent study adds significantly to the evidence that both peripheral and brain region-specific increases in tumour necrosis factor alpha lead to both sickness and depression- and anxiety disorder-relevant behavior and do so via different pathways [79]. Abnormalities in Toll-like receptor expression (TLR1-9) in depression have been observed in peripheral blood mononuclear cells and postmortem brains of depressed and suicidal patients [80]. The expression of TLR3, TLR4, TLR5, TLR7, TLR8 and TLR9 is elevated in depressed patients and antidepressant treatment completely normalizes TLR3, TLR5, TLR7, TLR8 and TLR9 levels, whereas TLR1, TLR2, TLR4, and TLR6 are decreased to below normal levels [75].…”

Section: Treat Inflammation In Depressionmentioning

confidence: 99%

Depression in the Context of Medical Disorders: New Pharmacological Pathways Revisited

Lang¹,

Walter²

2017

Neurosignals

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The depressive state has been characterised as one of elevated inflammation, changed cardiovascular parameters and a deranged metabolic situation all of which holds promise for a better understanding and handling of treatment-resistance in affective disorders as well as for future developments in treatment algorithms. In this context several biomarkers are differentially regulated by antidepressant treatment and connected to metabolic, inflammatory, cardiovascular and apoptotic components of the pathophysiology, i.e. adiponectin, apolipoprotein-B, B-type natriuretic peptide, cortisol, CRP, cysteine, homocysteine, fibrinogen, adiponectin, BMI, glycated hemoglobin A1c, leptin, interferon-gamma, high-density lipoprotein, interleukin interleukin-1alpha, -1beta, -2, -4, -5, -6, -8, -10, -12, -13, -17, insulin-like growth factor-1, low-density lipoprotein, myeloperoxidase, osteoprotegerin, tumour necrosis factor alpha, troponins, triglycerides etc. In this context antidepressants exert different modulatory effects on the outcome, incidence and mortality concerning several severe disorders, i.e. cancer, diabetes, stroke, inflammation, stroke and cardiovascular risk. Vice versa different drugs used in the treatment of these disorders have a favourable effect in depressive states, e.g. statins, aspirine, NSAIDs, pioglitazone, celecoxib, peroxisome proliferator-activated receptor-gamma agonists and minocycline. In this review, actions of different antidepressant treatment strategies on cancer, stroke, diabetes and cardiovascular disorders are shown and the influence on the outcome of the disorders is differentially discussed. In conclusion a hypothetic model for the implication of actual findings in everyday clinical practice is proposed. In this context personalized treatment could be used to tailor treatment to specific individuals according to their clinical endophenotypes. Moreover a potential target for the development of novel intervention strategies might be used.

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Antidepressants normalize elevated Toll-like receptor profile in major depressive disorder

Cited by 78 publications

References 48 publications

Antidepressants Improve Negative Regulation of Toll-Like Receptor Signaling in Monocytes from Patients with Major Depression

Antidepressants Improve Negative Regulation of Toll-Like Receptor Signaling in Monocytes from Patients with Major Depression

TNFAIP3 mRNA Level Is Associated with Psychological Anxiety in Major Depressive Disorder

Depression in the Context of Medical Disorders: New Pharmacological Pathways Revisited

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