Angelos Halaris ,Brandon Hage ,C. Sue Carter ,Hossein P. Nazarloo ,Jasleen Singh , Does Arginine Vasopressin Reflect HPA-axis Activation in Major Depressive Disorder? Clinical and Experimental Investigations 2020 2674-5054 http://dx.doi.org/10.31487/j.CEI.2020.02.01 https://www.sciencerepository.org/does-arginine-vasopressin-reflect_CEI-2020-2-101 Abstract: Researchers have endeavored to subclassify depressive illness based on pathophysiological mechanism. One model relates to hypothalamic-pituitary-adrenal (HPA) axis overactivation with a shift from corticotropin-releasing hormone (CRH) driven regulation to arginine vasopressin (AVP) driven regulation. Given the mixed literature, we compared plasma AVP levels in healthy controls to patients with major depressive disorder (MDD). Plasma samples from 33 patients and 12 controls were collected at baseline, 8 weeks, and 12 weeks of treatment and measured by immunochemical assay. Patients who were treatment responders trended toward lower AVP levels than non-responders. Patients were stratified into low and high AVP groups based on median split. Within the low AVP group, patients whose current episode lasted longer than a year had significantly higher baseline AVP levels than patients whose current episode was less than 6 months. Female patients in the low AVP group had significantly higher baseline AVP levels than male patients. Given the association between stress, HPA axis activation, immune dysregulation, and depression, we also measured concentrations of inflammatory biomarkers. We found a significant negative correlation between IL-10 and baseline AVP levels, within the low AVP subgroup. Given inconsistent data, HPA axis overactivation may be present within a subset of depressed patients.Keywords: Depression, Arginine vasopressin, HPA axis, Inflammation