Plasma levels of soluble TNF receptors 1 and 2 after tDCS and sertraline treatment in major depression: Results from the SELECT-TDCS trial

Abstract

Background: The cytokine hypothesis of depression postulates that the pathophysiology of this illness incorporates an increased production of pro-inflammatory cytokines, which leads to an over activation of the hypothalamic-pituitary-adrenal axis as well as monoaminergic disturbances. Nevertheless, it remains unclear whether the amelioration of depressive symptoms could decrease cytokine levels. Notwithstanding antidepressant drug therapy might exert anti-inflammatory effects, the effects of non-invasive neuromodulatory approaches like transcranial direct current stimulation (tDCS) on pro-inflammatory cytokine networks are largely unknown. Methods: We evaluated, in the Set-Leanne vs. Eleciric Curreni Therapy for TreaLing Depression Clinical SLudy (SELECT-TDCS) fetal, whether the plasma levels of the soluble TNF recepLors 1 and 2 (sTNFRs) changed tiller anLiclepressanL LreaLmeni in a sample of 73 anLidepressanL-free paLienis with unipolar depressive disorder in an episode of aL leasL mocleraLe inLensiLy. Results: Although boat LDCS and set-Leanne exerLed anLiclepressanL effecfs. the plasma levels of sTNFRs did noi change over Lime regardless of Lhe infervenLion and clinical response. Also, baseline sTNFRs levels did noL predicL anLiclepressanL response. Limitations: Our negative findings could be a type LI error, as this trial did not use an equivalence design. Conclusions: To conclude, in this novel placebo-controlled trial prospectively evaluating the changes of sTNFRs in depressed patients, we found that these molecules are not surrogate biomarkers of treatment I esponse of tDCS, whose antidepressant effects occurred regardless of normalization of immunological activity.