Abstract
RationaleAbnormalities 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.ObjectivesChanges 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.ResultsTLR3, 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.ConclusionsThese 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.
Highlights
Major depressive disorder (MDD) represents a combination of mood, cognition, sleep, and appetite disturbances that lasts for at least 2 weeks
Baseline Toll-like receptor (TLR) mRNA levels in patients compared with controls mRNA levels for six of the nine TLRs were significantly elevated in depressed patients at baseline compared with healthy controls
We found that TLR3 mRNA was elevated in peripheral blood mononuclear cells (PBMCs) of MDD patients (Hung et al 2014)
Summary
Major depressive disorder (MDD) represents a combination of mood, cognition, sleep, and appetite disturbances that lasts for at least 2 weeks. Depressive disorders are comorbid with other inflammatory diseases, including diabetes, cancer, cardiac disease, and metabolic syndrome (Evans et al 2005). The link between altered immune response and MDD has grown out of the observation that cytokine therapy for different diseases, especially treatment with interferon-α, is accompanied by depressive symptomatology (Capuron and Miller 2004; Miyaoka et al 1999). About one third of patients who receive recombinant human cytokines for the treatment of hepatitis C exhibit complicating depressive symptoms. Numerous additional proinflammatory cytokines in peripheral blood, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-8, have been reported to be elevated in different stage of MDD (Dowlati et al 2010). We have found significantly higher serum IL-1β levels and IL-1β/IL-10 ratios in patients with melancholic features compared with patients lacking these features (Huang and Lee 2007)
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