Effects of tDCS on neuroplasticity and inflammatory biomarkers in bipolar depression: Results from a sham-controlled study

Objectives: We investigated the role of peripheral biomarkers associated with neuroplasticity and immune-inflammatory processes on the effects of transcranial direct current stimulation (tDCS), a safe, affordable, and portable non-invasive neuromodulatory treatment, in bipolar depression. Methods: This is an exploratory analysis using a dataset from the sham-controlled study the Bipolar Depression Electrical Treatment Trial (BETTER)(clinicaltrials.gov NCT02152878). Participants were 52 adults with type I or II bipolar disorder in a moderate-to-severe depressive episode, randomized to 12 bifrontal active or sham tDCS sessions over a 6-week treatment course. Plasma levels of brain derived neurotrophic factor (BDNF), glial cell derived neurotrophic factor (GDNF), interleukins (IL) 2, 4, 6, 8, 10, 18, 33, 1β, 12p70, 17a, interferon gamma (IFN), tumor necrosis factor alpha (TNF) and its soluble receptors 1 and 2, ST2, and KLOTHO were investigated at baseline and endpoint. We performed analyses unadjusted for multiple testing to evaluate whether baseline biomarkers were predictive for depression improvement and changed during treatment using linear regression models. Results: A time x group interaction (Cohen's d: -1.16, 95% CI = −1.96 to −0.3, p =.005) was found for IL-8, with greater reductions after active tDCS. Higher baseline IL-6 plasma levels was associated with symptomatic improvement after tDCS (F_(1,43) = 5.43; p =.025). Other associations were not significant. Conclusions: Our exploratory findings suggested that IL-6 is a potential predictor of tDCS response and IL-8 might decrease after tDCS; although confirmatory studies are warranted due to the multiplicity of comparisons.