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

•TNF-α and its receptors TNFR1 and TNFR2 are involved in depression pathophysiology.•73 Patients with MDD were treated with tDCS, sertraline or both.•STNFRs plasma levels were collected at baseline and endpoint.•The plasma levels of these receptors did not change after successful treatment.•Inflammation may have a causal and small effect in MDD pathophysiology.

BackgroundThe 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.MethodsWe evaluated, in the Sertraline vs. Electric Current Therapy for Treating Depression Clinical Study (SELECT-TDCS) trial, whether the plasma levels of the soluble TNF receptors 1 and 2 (sTNFRs) changed after antidepressant treatment in a sample of 73 antidepressant-free patients with unipolar depressive disorder in an episode of at least moderate intensity.ResultsAlthough both tDCS and sertraline exerted antidepressant effects, the plasma levels of sTNFRs did not change over time regardless of the intervention and clinical response. Also, baseline sTNFRs levels did not predict antidepressant response.LimitationsOur negative findings could be a type II error, as this trial did not use an equivalence design.ConclusionsTo 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 response of tDCS, whose antidepressant effects occurred regardless of normalization of immunological activity.