Altered mRNA expressions for N-methyl-D-aspartate receptor-related genes in WBC of patients with major depressive disorder

Objective: Major depressive disorder (MDD) is a complex mental disorder. The lack of well-established biomarkers hinders its diagnosis, treatment, and new-drug development. N-methyl-D-aspartate receptor (NMDAR) dysfunction has been implicated in the pathogenesis of MDD. This study examined whether expressions of the NMDAR-related genes are characteristic of MDD. Methods: Expressions of NMDAR-related genes including SRR, SHMT2, PSAT1, GCAT, GAD1, SLC1A4, NRG1 and COMT in peripheral WBCs of 110 patients with MDD (25 drug-naive, 21 drug-free, and 64 medicated patients) and 125 healthy individuals were measured using quantitative PCR. Results: The mRNA expression levels of SRR, PSAT1, GCAT, GAD1, NRG1 and COMT were significantly different among the four groups (all p < 0.05). For drug-naive patients, the Delta Delta CT values of SRR, PSAT1, GCAT, GAD1, and NRG1 mRNA expressions were significantly different from those in healthy individuals (all p < 0.05). The ROC analysis of the Delta Delta CT values of the target genes for differentiating drug-naive patients from healthy controls showed an excellent sensitivity (0.960) and modest specificity (0.640) (AUC = 0.889). Drug-free and medicated patients obtained less favorable AUC values while compared to healthy controls. The results for the age-and sex-matched cohort were similar to those of the unmatched cohort. Conclusions: This is the first study demonstrating that the peripheral mRNA expression levels of NMDAR-related genes may be altered in patients with MDD, especially drug-naive individuals. The finding supports the NMDAR hypothesis of depression. Whether mRNA expresssion of NMDAR-related genes could serve as a potential biomarker of MDD deserves further investigations.