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

Abstract

BackgroundAccumulating 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. MethodsIn 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). ResultsFemales 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. LimitationsThis 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. ConclusionsWe 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.