There is growing evidence that aberrant transcriptional regulation is one of the key components of the pathophysiology of mood disorders. The repressor element-1 silencing transcription factor (REST) is a negative regulator of genes that contain the repressor element-1 (RE-1) binding site. REST has many target genes, including corticotropin releasing hormone (CRH), brain-derived neurotrophic factor, serotonin 1A receptor, which are suggested to be involved in the pathophysiology of depression and the action of antidepressants. However, a potential role for REST-mediated transcriptional regulation in mood disorders remains unclear. In this study, we examined the mRNA levels of REST and its known and putative target genes, using quantitative real-time PCR in peripheral blood cells of patients with major depressive and bipolar disorders in both a current depressive and a remissive state. We found reduced mRNA expression of REST and increased mRNA expression of CRH, adenylate cyclase 5, and the tumor necrosis factor superfamily, member 12-13 in patients with major depressive disorder in a current depressive state, but not in a remissive state. Altered expression of these mRNAs was not found in patients with bipolar disorder. Our results suggest that the aberrant REST-mediated transcriptional regulation of, at least, CRH, adenylate cyclase 5, and tumor necrosis factor superfamily, member 12-13, might be state-dependent and associated with the pathophysiology of major depression.