Differential expression of glutamate transporters and monoaminergic genes in major depression and suicide.

Abstract

Accumulating evidence indicates that the glutamate and monoamine systems contribute to the pathophysiology of major depressive disorder (MDD) and suicide. We have tested the expression of genes encoding glutamate transporters and monoaminergic proteins in the dorsolateral prefrontal cortex (DLPFC) of MDD subjects who died by suicide (MDD-S, n=51), MDD non-suicide subjects (MDD-NS, n=28), and non-psychiatric controls (CTRL, n=32). We analyzed glutamate transporters (EAAT1, EAAT2, VGLUT1, and VGLUT2) and monoaminergic genes (SERT, NET, DAT, PMAT, VMAT, TPH1 and TPH2). Females but not males with MDD showed higher expression of all glutamate transporters relative to CTRLs (P<0.05). MDD-S groups of both sexes had higher VGLUT2 expression (P<0.05). MDD-S females who were antidepressant positive (+) had lower EAAT1 expression (P=0.004), perhaps indicating poor treatment response. Analyses of monoaminergic genes revealed lower VMAT1 expression (P=0.002) in MDD males, and conversely higher VMAT2 in MDD females (P=0.004). MDD females also had higher VMAT2, TPH2 and NET expression (p<0.05), and in contrast, MDD males had lower VMAT1 and PMAT expression. Therefore, we report sex differences in the expression of glutamate transporters and some monoaminergic genes in the DLPFC in MDD. Most of these findings are novel, but lower EAAT1 expression in MDD-S replicates previous studies. Lower EAAT1 expression coupled with higher VGLUT2 expression in MDD-S may lead to increased synaptic glutamate, neuronal loss and glial loss in the DLPFC in MDD and suicide reported previously. These deficits may contribute to lower DLPFC activity, poor problem solving and impaired executive function exhibited in severe depression and suicide.