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The aim of the current study was to investigate whether the levels of mRNA expression of brain-derived neurotrophin factor (BDNF) and a related gene MEK1 were more obviously decreased in treatment-resistant depression (TRD). In total, 50 patients with major depressive disorder (including 26 with TRD and 24 with treatment-responsive depression) and 48 healthy controls were enrolled. BDNF and MEK1 mRNA levels in blood samples from all patients and controls were measured using reverse transcriptase-PCR. BDNF and MEK1 mRNA levels were significantly reduced in patients with major depressive disorder when compared with healthy controls (BDNF: P<0.01; MEK1: P<0.001), as well as among treatment-resistant depressive patients as compared with treatment-responsive depressive patients (BDNF: P<0.001; MEK1: P<0.01). Our findings support the hypothesis that BDNF and MEK1 mRNA expression levels are more obviously decreased in patients with TRD.