title: Cytokines plasma levels during antidepressant treatment with sertraline and transcranial direct current stimulation (tDCS): results from a factorial, randomized, controlled trial.
abstract: BACKGROUND
  The inflammatory hypothesis of depression states that increased levels of pro-inflammatory cytokines triggered by external and internal stressors are correlated to the acute depressive state. This hypothesis also suggests that pharmacotherapy partly acts in depression through anti-inflammatory effects. Transcranial direct current stimulation (tDCS) is a novel, promising, non-invasive somatic treatment for depression, although its antidepressant mechanisms are only partly understood.
  
  
  OBJECTIVE
  We explored the effects of tDCS and sertraline over the immune system during an antidepressant treatment trial.
  
  
  METHODS
  In a 6-week, double-blind, placebo-controlled trial, 73 antidepressant-free patients with unipolar depression were randomized to active/sham tDCS and sertraline/placebo (2 × 2 design). Plasma levels of several cytokines (IL-2, IL-4, IL-6, IL-10, IL-17a, IFN-γ, and TNF-α) were determined to investigate the effects of the interventions and of clinical response on them.
  
  
  RESULTS
  All cytokines, except TNF-α, decreased over time, these effects being similar across the different intervention-groups and in responders vs. non-responders.
  
  
  CONCLUSIONS
  tDCS and sertraline (separately and combined) acute antidepressant effects might not specifically involve normalization of the immune system. In addition, being one of the first placebo-controlled trials measuring cytokines over an antidepressant treatment course, our study showed that the decrease in cytokine levels during the acute depressive episode could involve a placebo effect, highlighting the need of further placebo-controlled trials and observational studies examining cytokine changes during depression treatment and also after remission of the acute depressive episode.
authors.affiliation: Center for Clinical and Epidemiological Research and Interdisciplinary Center for Applied Neuromodulation (CINA), University Hospital, University of São Paulo, Av. Prof Lineu Prestes 2565, 3o andar, CEP 05508-000, São Paulo, São Paulo, Brazil, brunoni@usp.br.
authors.forename: André R
authors.initials: AR
authors.lastname: Brunoni
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Machado-Vieira
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Zarate
authors.forename: Leandro
authors.initials: L
authors.lastname: Valiengo
authors.forename: Erica Lm
authors.initials: EL
authors.lastname: Vieira
authors.forename: Isabela M
authors.initials: IM
authors.lastname: Benseñor
authors.forename: Paulo A
authors.initials: PA
authors.lastname: Lotufo
authors.forename: Wagner F
authors.initials: WF
authors.lastname: Gattaz
authors.forename: Antonio L
authors.initials: AL
authors.lastname: Teixeira
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D016207:Cytokines / Q000097:blood*; D003866:Depressive Disorder / Q000097:blood / Q000188:drug therapy* / Q000628:therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020280:Sertraline / Q000494:pharmacology / Q000627:therapeutic use*; D065908:Transcranial Direct Current Stimulation; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D016207:Cytokines; D020280:Sertraline