The gene coding for oxytocin is hypomethylated in patients with Major Depressive Disorder compared to healthy controls.

This pattern was consistently found for mean methylation and single CpG units.

This pre-registered replication study shows that hypomethylation of the oxytocin gene is reproducibly associated with Major Depressive Disorder and should be further investigated regarding its role in depression development or course of the disorder.

Depression is linked to stress which leaves traces in the epigenetic signature of genes. The oxytocin system is implicated in allostatic processes promoting adaption to environmental stressors. Interactions of the oxytocin system with the environment, e.g., methylation of the gene coding for oxytocin (OXT), are candidates for the investigation of the biological underpinnings of depression. Recently, we found hypomethylation of OXT in patients with Major Depressive Disorder (MDD) compared to healthy controls (HC). Since the replicability of findings is a key point of criticism in (epi‑)genetic research, we aimed to confirm our previous findings in a pre-registered study (data was stored in a database prior to pre-registration) within a new sample of n = 85 patients with MDD and n = 85 HC. We investigated OXT DNA-methylation in peripheral blood samples, stressful life events and depression severity. In accordance with our previous study, we found hypomethylation of OXT in patients with MDD compared to HC. Methylation was not associated with stressful life events. Patients reported significantly more stressful life events compared to HC. Our study revealed that hypomethylation of OXT can be demonstrated in a reproducible fashion and provides further evidence for the involvement of the oxytocin system in depression.

Depression

Oxytocin

Methylation

Case control

Stress

© 2024 The Author(s). Published by Elsevier B.V.