title: Evidence for increased motor cortical facilitation and decreased inhibition in atypical depression.
abstract: Major depressive disorder (MDD) is a clinically heterogeneous condition. However, the role of cortical glutamate and gamma-aminobutyric acid (GABA) receptor-mediated activity, implicated in MDD pathophysiology, has not been explored in different MDD subtypes. Our aim was to assess the atypical and melancholic depression subtypes regarding potential differences in GABA and glutamate receptor-mediated activity through established transcranial magnetic stimulation (TMS) neurophysiological measures from the motor cortex.
  
  
  
  We evaluated 81 subjects free of antidepressant medication, including 21 healthy controls and 20 patients with atypical, 20 with melancholic, and 20 with undifferentiated MDD. Single and paired-pulse TMS paradigms were used to evaluate intracortical facilitation (ICF), cortical silent period (CSP), and short intracortical inhibition (SICI), which index glutamate, GABAB receptor-, and GABAA receptor-mediated activity respectively.
  
  
  
  Patients with MDD demonstrated significantly decreased mean CSP values than healthy controls (Cohen's d = 0.22-0.3, P < 0.01 for all comparisons). Atypical depression presented a distinct cortical excitability pattern of decreased cortical inhibition and increased cortical facilitation, that is, an increased mean ICF and SICI ratios than other depression subtypes (d = 0.22-0.33, P < 0.01 for all comparisons).
  
  
  
  Different MDD subtypes may demonstrate different neurophysiology in relation to GABAA and glutamatergic activity. TMS as an investigational tool might be useful to distinguish between different MDD subtypes.
authors.affiliation: Interdisciplinary Center for Applied Neuromodulation, University Hospital, University of Sao Paulo, São Paulo, Brazil.
authors.forename: B P
authors.initials: BP
authors.lastname: Veronezi
authors.affiliation: Interdisciplinary Center for Applied Neuromodulation, University Hospital, University of Sao Paulo, São Paulo, Brazil.
authors.forename: A H
authors.initials: AH
authors.lastname: Moffa
authors.affiliation: Department of Psychiatry and Translational Psychiatry Research Group, Faculty of Medicine, Federal University of Ceará, Fortaleza, Ceara, Brazil.
authors.forename: A F
authors.initials: AF
authors.lastname: Carvalho
authors.affiliation: Service of Interdisciplinary Neuromodulation, Laboratory of Neurosciences (LIM-27), Department and Institute of Psychiatry, University of São Paulo, São Paulo, Brazil.|School of Arts, Science and Humanities, University of São Paulo, São Paulo, Brazil.|Pain Center, Department of Neurology, University of São Paulo, São Paulo, Brazil.|Medicine School of University City of São Paulo (UNICID), São Paulo, Brazil.
authors.forename: R
authors.initials: R
authors.lastname: Galhardoni
authors.affiliation: Institute of Physical Medicine and Rehabilitation, Clinics Hospital of the University of Sao Paulo Medical School, São Paulo, Brazil.
authors.forename: M
authors.initials: M
authors.lastname: Simis
authors.affiliation: Interdisciplinary Center for Applied Neuromodulation, University Hospital, University of Sao Paulo, São Paulo, Brazil.
authors.forename: I M
authors.initials: IM
authors.lastname: Benseñor
authors.affiliation: Interdisciplinary Center for Applied Neuromodulation, University Hospital, University of Sao Paulo, São Paulo, Brazil.
authors.forename: P A
authors.initials: PA
authors.lastname: Lotufo
authors.affiliation: Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health (NIH), Bethesda, MD, USA.
authors.forename: R
authors.initials: R
authors.lastname: Machado-Vieira
authors.affiliation: Temerty Centre for Therapeutic Brain Intervention and Campbell Family Research Institute, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
authors.forename: Z J
authors.initials: ZJ
authors.lastname: Daskalakis
authors.affiliation: Interdisciplinary Center for Applied Neuromodulation, University Hospital, University of Sao Paulo, São Paulo, Brazil.|Service of Interdisciplinary Neuromodulation, Laboratory of Neurosciences (LIM-27), Department and Institute of Psychiatry, University of São Paulo, São Paulo, Brazil.
authors.forename: A R
authors.initials: AR
authors.lastname: Brunoni
mesh_terms: D000328:Adult; D003865:Major Depressive Disorder / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000378:metabolism / Q000503:physiopathology*; D018079:Receptors, GABA / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism; D050781:Transcranial Magnetic Stimulation / Q000379:methods*; D055815:Young Adult
chemical_list: D018079:Receptors, GABA; D017470:Receptors, Glutamate
keywords: gamma-aminobutyric acid; glutamate; major depressive disorder; motor cortex excitability; transcranial magnetic stimulation