Alterations in the neuropeptide galanin system in major depressive disorder involve levels of transcripts, methylation, and peptide

Significance Depression is a seriously disabling disorder, twice as common in women as in men. Lack of efficacy of existing pharmacotherapies in subsets of patients has led to an intensive search for new targets for antidepressant development, including receptors for neuropeptides such as galanin (GAL). In this study, we explore GAL and its three receptors, GAL 1–3 , comparing postmortem brain regions from depressed suicide patients and controls. Using quantitative PCR and bisulfite pyrosequencing, we report significant changes in the transcript and DNA methylation levels of GAL and galanin receptor 3 ( GALR3 ) in the locus coeruleus and dorsal raphe nucleus, two regions important for mood regulation. Our findings suggest GAL 3 involvement in depressive disorder, making it a possible drug target for this disease.