title: Marked reductions in visual evoked responses but not γ-aminobutyric acid concentrations or γ-band measures in remitted depression.
abstract: BACKGROUND
  Magnetic resonance spectroscopy (MRS) studies have consistently demonstrated reduced cortical γ-aminobutyric acid (GABA) concentrations in individuals with major depression. However, evidence for a persistent deficit during remission, which would suggest that GABA dysfunction is a possible trait marker of depression, is equivocal. Although MRS measures total concentration of GABA, magneto-encephalography provides direct measures of neural activity, with cortical γ oscillations shaped by the activity of GABAergic inhibitory interneurons. In this study we investigated whether γ oscillations and GABA concentrations would differ in individuals with remitted depression (RD) compared with never depressed control subjects (ND).
  
  
  METHODS
  Thirty-seven healthy, unmedicated female volunteers (n = 19 RD, and n = 18 ND) were recruited. The γ oscillation frequencies and amplitudes in the visual cortex, induced by simple grating stimuli, were quantified with time-frequency analyses. Distinct GABA/glutamate + glutamine MRS peaks were resolved from MEGA-PRESS difference spectra in prefrontal, occipital, and subcortical volumes.
  
  
  RESULTS
  The RD and ND individuals did not differ in the frequency of subclinical depressive symptoms. The ND were slightly older (mean = 23 years vs. 21 years), but age did not correlate with dependent measures. There were no group differences in GABA levels or induced cortical γ measures, but RD individuals had markedly reduced M80 (C1) components of the pattern-onset evoked response (46% reduction, Cohen's d = 1.01, p = .006).
  
  
  CONCLUSIONS
  Both MRS and magneto-encephalography measures of the GABA system are normal in RD. However, the early visual evoked response is a potential trait marker of the disorder.
authors.affiliation: Institute of Neuroscience and Mental Health, MRC Centre for Neuropsychiatric Genetics and Genomics, Henry Wellcome Building, Cardiff University, Heath Park, Cardiff CF14 4XN, United Kingdom.
authors.forename: Alexander
authors.initials: A
authors.lastname: Shaw
authors.forename: Jennifer
authors.initials: J
authors.lastname: Brealy
authors.forename: Heather
authors.initials: H
authors.lastname: Richardson
authors.forename: Suresh D
authors.initials: SD
authors.lastname: Muthukumaraswamy
authors.forename: Richard A
authors.initials: RA
authors.lastname: Edden
authors.forename: C
authors.initials: C
authors.lastname: John Evans
authors.forename: Nicolaas A J
authors.initials: NA
authors.lastname: Puts
authors.forename: Krishna D
authors.initials: KD
authors.lastname: Singh
authors.forename: Paul A
authors.initials: PA
authors.lastname: Keedwell
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000378:metabolism / Q000502:physiology; D058256:Brain Waves / Q000502:physiology*; D016022:Case-Control Studies; D003863:Depression / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology*; D005074:Evoked Potentials, Visual / Q000502:physiology*; D005260:Female; D059907:Functional Neuroimaging / Q000523:psychology; D018698:Glutamic Acid / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D006801:Humans; D014793:Visual Cortex / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D005973:Glutamine; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid