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Sex differences in the transcription of glutamate transporters in major depression and suicide.

Authors
  • Powers, Brian1
  • Joyce, Cara2
  • Kleinman, Joel E3
  • Hyde, Thomas M4
  • Ajilore, Olusola5
  • Leow, Alex5
  • Sodhi, Monsheel S6
  • 1 Department of Molecular Pharmacology & Neuroscience, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153, United States. , (United States)
  • 2 Biostatistics Collaborative Core, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, United States. , (United States)
  • 3 Lieber Institute for Brain Development and Department of Psychiatry & Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, United States. , (United States)
  • 4 Lieber Institute for Brain Development and Department of Psychiatry & Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, United States; Johns Hopkins University School of Medicine, Department of Neurology, Baltimore, MD, United States. , (United States)
  • 5 Dept. Psychiatry, University of Illinois at Chicago, Chicago, IL, United States. , (United States)
  • 6 Department of Molecular Pharmacology & Neuroscience, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153, United States; Dept. Psychiatry, University of Illinois at Chicago, Chicago, IL, United States. Electronic address: [email protected] , (United States)
Type
Published Article
Journal
Journal of affective disorders
Publication Date
Dec 01, 2020
Volume
277
Pages
244–252
Identifiers
DOI: 10.1016/j.jad.2020.07.055
PMID: 32836031
Source
Medline
Language
English
License
Unknown

Abstract

Accumulating evidence indicates that the glutamate system contributes to the pathophysiology of major depressive disorder (MDD) and suicide. We previously reported higher mRNA expression of glutamate receptors in the dorsolateral prefrontal cortex (DLPFC) of females with MDD. In the current study, we measured the expression of mRNAs encoding glutamate transporters in the DLPFC of MDD subjects who died by suicide (MDD-S, n = 51), MDD non-suicide subjects (MDD-NS, n = 28), and individuals who did not have a history of neurological illness (CTRL, n = 32). Females but not males with MDD showed higher expression of EAATs and VGLUTs relative to CTRLs. VGLUT expression was significantly higher in the female MDD-S group, relative to the other groups. EAAT expression was lower in the male violent suicides. This study has limitations common to most human studies, including medication history and demographic differences between the diagnostic groups. We mitigated the effects of confounders by including them as covariates in our analyses. We report sex differences in the expression of glutamate transporter genes in the DLPFC in MDD. Increased neuronal glutamate transporter expression may increase synaptic glutamate, leading to neuronal and glial loss in the DLPFC in MDD. These deficits may lower DLPFC activity, impair problem solving and impair executive function in depression, perhaps increasing vulnerability to suicidal behavior. These data add to accumulating support for the hypothesis that glutamatergic transmission is dysregulated in MDD and suicide. Glutamate transporters may be novel targets for the development of rapidly acting antidepressant therapies. Copyright © 2020. Published by Elsevier B.V.

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