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

Abstract

Rationale Abnormalities in Toll-like receptor (TLR) expression in depression have been inferred in part from observed increases in TLR4 levels in peripheral blood mononuclear cells (PBMCs) and postmortem brains of depressed and suicidal patients. Our previous study found differences in the TLR expression in PBMCs between healthy controls and patients with major depressive disorder. Normalization of increased TLR4 in PBMCs by cognitive behavior psychotherapy has been reported. However, the effects of antidepressants remain unknown. Objectives Changes in TLR1-9 expression levels of PBMCs were examined in 56 patients with MDD. The 17-item Hamilton Depression Rating Scale (HAMD-17) and mRNA expression levels of TLRs were assessed in parallel with a housekeeping gene using qRT-PCR before and after treatment with antidepressants. Results TLR3, TLR4, TLR5, TLR7, TLR8, and TLR9 were expressed at elevated levels in patients with MDD and were significantly decreased by treatment with antidepressants for 4 weeks. Antidepressant treatment completely normalized TLR3, TLR5, TLR7, TLR8, and TLR9 levels, whereas TLR1, TLR2, TLR4, and TLR6 were decreased to below normal levels. A subgroup analysis found that only TLR3 was significantly higher at baseline in the nonremission group. In addition, a multiple linear regression analysis revealed that only low TLR3 before treatment predicted improvement in HAMD-17 scores. Conclusions These findings suggest that antidepressant treatment exerts anti-inflammatory effects in patients with MDD and identify TLR profiles as a predictor of response to antidepressant therapy. Further studies investigating the effects of manipulating individual TLRs on depression are needed to fully elucidate the underlying mechanism.

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

“…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]. …”

“…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].…”

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

“…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′).…”

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

“…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].…”