Sex differences in the transcription of glutamate transporters in major depression and suicide.
Journal
Journal of affective disorders
ISSN: 1573-2517
Titre abrégé: J Affect Disord
Pays: Netherlands
ID NLM: 7906073
Informations de publication
Date de publication:
01 12 2020
01 12 2020
Historique:
received:
26
07
2019
revised:
29
05
2020
accepted:
05
07
2020
pubmed:
25
8
2020
medline:
6
3
2021
entrez:
25
8
2020
Statut:
ppublish
Résumé
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.
Sections du résumé
BACKGROUND
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.
METHODS
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).
RESULTS
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.
LIMITATIONS
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.
CONCLUSIONS
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.
Identifiants
pubmed: 32836031
pii: S0165-0327(20)32500-3
doi: 10.1016/j.jad.2020.07.055
pii:
doi:
Substances chimiques
Amino Acid Transport System X-AG
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
244-252Informations de copyright
Copyright © 2020. Published by Elsevier B.V.