title: 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 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.
  
  
  RESULTS
  Although 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.
  
  
  CONCLUSIONS
  Our negative findings could be a type II 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 response of tDCS, whose antidepressant effects occurred regardless of normalization of immunological activity.
authors.affiliation: Center for Clinical and Epidemiological Research & Interdisciplinary Center for Applied Neuromodulation (CINA), University Hospital, University of São Paulo, São Paulo, Brazil; Service of Interdisciplinary Neuromodulation (SIN), Department and Institute of Psychiatry, Faculty of Medicine of University of São Paulo, São Paulo, Brazil; Laboratory of Neuroscience (LIM27), Department and Institute of Psychiatry, University of São Paulo, São Paulo, Brazil. Electronic address: Brunoni@usp.br.
authors.forename: André R
authors.initials: AR
authors.lastname: Brunoni
authors.affiliation: Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health (NIMH), NIH, Bethesda, MD, USA.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Machado-Vieira
authors.affiliation: Center for Clinical and Epidemiological Research & Interdisciplinary Center for Applied Neuromodulation (CINA), University Hospital, University of São Paulo, São Paulo, Brazil; Service of Interdisciplinary Neuromodulation (SIN), Department and Institute of Psychiatry, Faculty of Medicine of University of São Paulo, São Paulo, Brazil; Laboratory of Neuroscience (LIM27), Department and Institute of Psychiatry, University of São Paulo, São Paulo, Brazil.
authors.forename: Bernardo
authors.initials: B
authors.lastname: Sampaio-Junior
authors.affiliation: Division of Neuroscience, Interdisciplinary Laboratory of Medical Investigation (LIIM), School of Medicine, Federal University of Minas Gerais (UFMG), Belo Horizonte, Brazil.
authors.forename: Erica L M
authors.initials: EL
authors.lastname: Vieira
authors.affiliation: Center for Clinical and Epidemiological Research & Interdisciplinary Center for Applied Neuromodulation (CINA), University Hospital, University of São Paulo, São Paulo, Brazil; Service of Interdisciplinary Neuromodulation (SIN), Department and Institute of Psychiatry, Faculty of Medicine of University of São Paulo, São Paulo, Brazil; Laboratory of Neuroscience (LIM27), Department and Institute of Psychiatry, University of São Paulo, São Paulo, Brazil.
authors.forename: Leandro
authors.initials: L
authors.lastname: Valiengo
authors.affiliation: Center for Clinical and Epidemiological Research & Interdisciplinary Center for Applied Neuromodulation (CINA), University Hospital, University of São Paulo, São Paulo, Brazil.
authors.forename: Isabela M
authors.initials: IM
authors.lastname: Benseñor
authors.affiliation: Center for Clinical and Epidemiological Research & Interdisciplinary Center for Applied Neuromodulation (CINA), University Hospital, University of São Paulo, São Paulo, Brazil.
authors.forename: Paulo A
authors.initials: PA
authors.lastname: Lotufo
authors.affiliation: Department of Clinical Medicine and Translational Pychiatry Research Group, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil.
authors.forename: André F
authors.initials: AF
authors.lastname: Carvalho
authors.affiliation: Cousins Center for Psychoneuroimmunology, UCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles, CA, USA.
authors.forename: Hyong Jin
authors.initials: HJ
authors.lastname: Cho
authors.affiliation: Laboratory of Neuroscience (LIM27), Department and Institute of Psychiatry, University of São Paulo, São Paulo, Brazil.
authors.forename: Wagner F
authors.initials: WF
authors.lastname: Gattaz
authors.affiliation: Division of Neuroscience, Interdisciplinary Laboratory of Medical Investigation (LIIM), School of Medicine, Federal University of Minas Gerais (UFMG), Belo Horizonte, Brazil.
authors.forename: Antonio L
authors.initials: AL
authors.lastname: Teixeira
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000628:therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood*; D020280:Sertraline / Q000627:therapeutic use*; D065908:Transcranial Direct Current Stimulation; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D020280:Sertraline
keywords: Major depressive disorder; STNFR1; STNFR2; Sertraline; Transcranial direct current stimulation