Sex differences in the transcription of monoamine transporters in major depression

Abstract

Background: Accumulating evidence indicates that reduced activity within the monoamine systems contributes to the pathophysiology of major depressive disorder (MDD) and suicide. In this study, we have tested the hypothesis that monoaminergic gene transcription is abnormally regulated in MDD and suicide.

Methods: The transcription of specific monoaminergic genes was quantified by qPCR in the dorsolateral prefrontal cortex (DLPFC) of postmortem MDD subjects (n = 80) and non-psychiatric controls (CTRL, n = 32). We measured transcripts encoding monoaminergic transporters (the serotonin transporter (SERT), norepinephrine transporter (NET), dopamine transporter (DAT), plasma monoamine transporter (PMAT), vesicular monoamine transporter (VMAT)) in addition to the tryptophan hydroxylase (TPH) enzymes, TPH1 and TPH2. We tested for transcriptional differences between diagnostic groups and tested for differences in the depressed suicides.

Results: Multivariate analysis of monoaminergic gene transcription revealed a sex by diagnosis interaction (F_8,99 = 2.87, p = 0.007). We report lower VMAT1 and PMAT expression in depressed males, and conversely higher VMAT2, TPH2 and NET expression in depressed females, relative to controls of the same sex (p < 0.05). We did not detect differences in monoamine gene transcription between the depressed suicides and depressed non-suicides.

Limitations: Gene expression measures were not associated with the presence of antidepressant medication. Nevertheless, to minimize the impact of medication status and other potential confounding variables, these were included as covariates in our analyses.

Conclusions: We report sex differences in the transcription of monoaminergic genes in the DLPFC in MDD. Therefore abnormalities of monoaminergic gene expression may contribute to altered DLPFC activity exhibited in major depression.

Keywords: Dopamine; Dorsolateral prefrontal cortex; Norepinephrine; Postmortem; Serotonin; mRNA.