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Marked Reductions in Visual Evoked Responses But Not γ-Aminobutyric Acid Concentrations or γ-Band Measures in Remitted Depression

  • Alexander Shaw
    Affiliations
    Institute of Neuroscience and Mental Health, MRC Centre for Neuropsychiatric Genetics and Genomics, Henry Wellcome Building, Cardiff University, Heath Park
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  • Jennifer Brealy
    Affiliations
    Institute of Neuroscience and Mental Health, MRC Centre for Neuropsychiatric Genetics and Genomics, Henry Wellcome Building, Cardiff University, Heath Park
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  • Heather Richardson
    Affiliations
    Cardiff University Brain Research Imaging Centre, School of Psychology, Cardiff University, Park Place, Cardiff, Wales, United Kingdom
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  • Suresh D. Muthukumaraswamy
    Affiliations
    Cardiff University Brain Research Imaging Centre, School of Psychology, Cardiff University, Park Place, Cardiff, Wales, United Kingdom
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  • Richard A. Edden
    Affiliations
    Russell H Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine

    FM Kirby Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland
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  • C. John Evans
    Affiliations
    Cardiff University Brain Research Imaging Centre, School of Psychology, Cardiff University, Park Place, Cardiff, Wales, United Kingdom
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  • Nicolaas A.J. Puts
    Affiliations
    Russell H Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine

    FM Kirby Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland
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  • Krishna D. Singh
    Affiliations
    Cardiff University Brain Research Imaging Centre, School of Psychology, Cardiff University, Park Place, Cardiff, Wales, United Kingdom
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  • Paul A. Keedwell
    Correspondence
    Address correspondence to Paul A. Keedwell, M.B., Ch.B., M.R.C.Psych., Ph.D., Honorary Consultant Psychiatrist, Clinical Lecturer in the Neurobiology of Mood Disorders, 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
    Affiliations
    Institute of Neuroscience and Mental Health, MRC Centre for Neuropsychiatric Genetics and Genomics, Henry Wellcome Building, Cardiff University, Heath Park
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Published:November 30, 2012DOI:https://doi.org/10.1016/j.biopsych.2012.09.032

      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.

      Key Words

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