Plasma biomarkers in a placebo-controlled trial comparing tDCS and escitalopram efficacy in major depression

Transcranial direct current stimulation (tDCS) holds promise as a therapeutic intervention for major depressive disorder (MDD). A more precise understanding of its underlying mechanisms may aid in the identification of subsets of patients responsive to tDCS within the context of precision psychiatry. In this ancillary investigation of the Escitalopram vs. Electrical Current Therapy for Treating Depression Clinical Study (ELECT-TDCS), we investigated whether plasma levels of several cytokines and neurotrophic factors associated with major depression or antidepressant response predicted tDCS effects. We examined, in 236 patients at 3 timepoints during a 10-week treatment course, plasma levels of nerve growth factor (NGF), brain-derived (BDNF), glial-cell line derived neurotrophic factor (GDNF), the interleukins (IL) IL-1ß, IL-6, IL-8, IL-10, IL-12p70, IL-18, IL-33, tumor necrosis factor-alpha (TNF-alpha), and its soluble receptors sTNFr1 and sTNFr2. General linear models and mixed-models analyses of variance were used to respectively assess whether plasma levels of these molecules (1) predicted tDCS antidepressant improvement and (2) changed over time. After correction for multiple comparisons (false discovery rate method), NGF baseline levels predicted early depression improvement for tDCS vs. escitalopram, whilst other biomarkers did not significantly predict treatment improvement. The levels of IL12p70, IL10, IL-1ß, IL-8 and sTNFr1 decreased over time, regardless of allocation group and clinical response. In general, peripheral biomarkers were not associated with the outcome. The post-hoc finding of baseline NGF levels predicting early depression improvement for tDCS should be explored in further studies.