GRIN2B gene expression is increased in the anterior cingulate cortex in major depression

Area of Science:

• Neurobiology
• Psychiatry
• Molecular Psychiatry

Background:

• The glutamatergic system is implicated in major depressive disorder (MDD) and psychosis.
• N-methyl-D-aspartate receptor (NMDAR) antagonists show promise for MDD treatment, yet NMDAR expression in MDD remains poorly understood.

Purpose of the Study:

• To investigate the gene expression of major NMDAR subunits in the anterior cingulate cortex (ACC) of individuals with MDD, with and without psychosis, compared to controls.
• To explore potential alterations in NMDAR composition and their implications for MDD neurobiology.

Main Methods:

• Quantitative real-time PCR (qRT-PCR) was used to measure the mRNA expression of NMDAR subunits (GRIN1, GRIN2A, GRIN2B).
• Gene expression analysis was performed on samples from the ACC of MDD subjects (with and without psychosis) and non-psychiatric controls.

Main Results:

• GRIN2B mRNA levels were significantly increased in MDD subjects without psychosis (+40%) and with psychosis (+32%) compared to controls.
• A trend towards increased GRIN1 mRNA was observed in MDD overall (+24%).
• MDD with psychosis showed a significant decrease in the GRIN2A:GRIN2B mRNA ratio (-19%).

Conclusions:

• These findings suggest glutamatergic system dysfunction at the gene expression level in the ACC in MDD.
• Altered NMDAR subunit expression, particularly increased GRIN2B and a changed GRIN2A:GRIN2B ratio in psychotic depression, may disrupt NMDAR composition in the ACC.
• This disruption could enhance signaling via GluN2B-containing NMDARs, potentially increasing glutamate excitotoxicity and supporting research into GluN2B antagonist treatments for MDD.