Work

Increased oxytocin/vasopressin ratio in bipolar disorder in a cohort of human postmortem adults

Year: 2025

Type: article

Abstract: Bipolar disorder (BD) and major depressive disorder (MDD) share some common characteristics in stress-related brain circuits, but they also exhibit distinct symptoms. Our previous postmortem research on the immunoreactivity (ir) levels of neuropeptide oxytocin (OT) in the hypothalamic paraventricular nucleus (OT PVN ) and some clinical research on plasma OT levels suggested that increased levels of OT is a potential trait marker for BD. However, dysregulation of the related neuropeptide arginine vasopressin (AVP), that often shows opposite effects for stress responses compared to OT has not been investigated in BD. Moreover, it remains so far unknown what the contribution may be of OT produced in the hypothalamic supraoptic nucleus (SON), another major source of OT (OT SON ). Therefore, in the present postmortem study, alterations in levels of OT-ir and for the first time in AVP-ir were determined in the SON and PVN among patients with BD, MDD, and matched controls. We observed a significantly increased OT PVN -ir but relatively stable AVP PVN -ir in male BD, and a significantly decreased AVP PVN -ir but relatively stable OT PVN -ir in female BD patients. A significantly increased ratio of OT-ir/AVP-ir was observed only in BD patients in both, the PVN and SON. No significant changes in OT-ir or AVP-ir were found in MDD patients compared with controls. Our data illustrate a clear disease- and sex-specificity of the OT and AVP changes in BD. In addition, since increased AVP-ir was observed in female BD patients with lithium nephropathy, increased AVP may have a direct effect on symptoms of BD. • Bipolar disorder (BD) and major depressive disorder (MDD) show distinct symptoms. • Increased hypothalamic paraventricular oxytocin OT PVN -ir was found in male BD. • Decreased vasopressin AVP PVN -ir was found in female BD. • Increased ratio of hypothalamic OT-ir/AVP-ir was found in BD but not MDD patients • Sex-specific changes in OT and AVP may serve as trait biomarkers for BD

Source: Neurobiology of Disease

DOI: 10.1016/j.nbd.2025.106904