The Complex Role of Oxytocin in Major Depressive Disorder

Objective: One proposed mechanism to subclassify depressive illness relates oxytocinergic dysregulation, via its effect on social behavior and Hypothalamic-pituitary-adrenal (HPA) axis inhibition. To further investigate the role of oxytocin in Major Depressive Disorder (MDD), we compared plasma oxytocin levels in patients with MDD to healthy controls. Methods: Plasma samples from 12 healthy controls and 33 MDD patients were collected at baseline, 8 weeks, and 12 weeks of treatment and oxytocin was measured by enzyme-immunoassay. Depression and anxiety scales were administered at screening, baseline, and at weeks 2, 4, 8, and 12 of treatment. Additionally, we investigated possible associations between blood concentrations of inflammatory biomarkers and oxytocin. Results: The average baseline oxytocin level was 429 pg/ml in MDD patients and 392 pg/ml in healthy control subjects. A significant negative correlation was found between baseline oxytocin and BMI. Treatment responders had significantly lower baseline oxytocin levels than non-responders. After stratifying patients into low and high oxytocin groups based on a median split, within the high oxytocin group, patients with no prior depressive episodes had significantly higher baseline oxytocin levels. A Chi-square distribution test revealed that African American patients were more likely to belong to the high baseline oxytocin group while Caucasian and Hispanic patients were more likely to belong to the low baseline oxytocin group. We found significant correlations between oxytocin and Von-Willebrand Factor (VWF) and Epidermal Growth Factor (EGF), only within the high oxytocin subgroup. There were no other significant correlations between baseline oxytocin and any other biomarkers. Conclusion: Within our limited patient cohort, our data adds to the mixed literature regarding the role of oxytocin in MDD. Oxytocinergic dysregulation and confounding factors may play a role for a subset of depressed patients.