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

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.