Gene expression of GABA and glutamate pathway markers in the prefrontal cortex of non-suicidal elderly depressed patients

Background: The prefrontal cortex (PFC) is presumed to be involved in the pathogenesis of depression.

Methods: We determined the gene expression of 32 markers of the pathways of the two main neurotransmitters of the PFC, gamma-aminobutyric acid (GABA) and l-glutamic acid (glutamate), by real-time quantitative PCR in human postmortem anterior cingulate cortex (ACC) and dorsolateral PFC (DLPFC) in elderly non-suicidal patients with major depressive disorder (MDD) or bipolar disorder (BD).

Results: We found the transcript levels of GABA(A) receptor beta 2 (GABRB2) and post-synaptic density-95 (PSD-95) to be significantly decreased in the ACC in mood disorder. DLPFC mRNA expression of all the detected genes in the mood disorder group did not differ significantly from that of the non-psychiatric controls.

Limitations: Several inherent and potentially confounding factors of a postmortem study, such as medication and cause of death, did not seem to affect the conclusions. The group size was relatively small but well documented, both clinically and neuropathologically.

Conclusions: The observed alterations in the GABAergic and glutamatergic pathways indicate a diminished activity. These alterations were only present in the ACC and not in the DLPFC.