title: Assessment of non-BDNF neurotrophins and GDNF levels after depression treatment with sertraline and transcranial direct current stimulation in a factorial, randomized, sham-controlled trial (SELECT-TDCS): an exploratory analysis.
abstract: The neurotrophic hypothesis of depression states that the major depressive episode is associated with lower neurotrophic factors levels, which increase with amelioration of depressive symptoms. However, this hypothesis has not been extended to investigate neurotrophic factors other than the brain-derived neurotrophic factor (BDNF). We therefore explored whether plasma levels of neurotrophins 3 (NT-3) and 4 (NT-4), nerve growth factor (NGF) and glial cell line derived neurotrophic factor (GDNF) changed after antidepressant treatment and correlated with treatment response. Seventy-three patients with moderate-to-severe, antidepressant-free unipolar depression were assigned to a pharmacological (sertraline) and a non-pharmacological (transcranial direct current stimulation, tDCS) intervention in a randomized, 2 × 2, placebo-controlled design. The plasma levels of NT-3, NT-4, NGF and GDNF were determined by enzyme-linked immunosorbent assay before and after a 6-week treatment course and analyzed according to clinical response and allocation group. We found that tDCS and sertraline (separately and combined) produced significant improvement in depressive symptoms. Plasma levels of all neurotrophic factors were similar across groups at baseline and remained significantly unchanged regardless of the intervention and of clinical response. Also, baseline plasma levels were not associated with clinical response. To conclude, in this 6-week placebo-controlled trial, NT-3, NT-4, NGF and GDNF plasma levels did not significantly change with sertraline or tDCS. These data suggest that these neurotrophic factors are not surrogate biomarkers of treatment response or involved in the antidepressant mechanisms of tDCS.
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: Laboratory of Neuroscience (LIM27), Department and Institute of Psychiatry, University of São Paulo, São Paulo, Brazil; 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: Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health (NIMH), NIH, Bethesda, MD, USA.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Zarate
authors.affiliation: Interdisciplinary Laboratory of Medical Investigation, Faculty of Medicine of Minas Gerais, 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: 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: Interdisciplinary Laboratory of Medical Investigation, Faculty of Medicine of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Antonio L
authors.initials: AL
authors.lastname: Teixeira
mesh_terms: D000328:Adult; D003865:Major Depressive Disorder / Q000097:blood / Q000628:therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009414:Nerve Growth Factors / Q000097:blood*; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D020280:Sertraline / Q000627:therapeutic use*; D065908:Transcranial Direct Current Stimulation
chemical_list: D009414:Nerve Growth Factors; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline
keywords: GDNF; Major depressive disorder; Neurotrophins; Sertraline; Transcranial direct current stimulation