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

• Published in: Neurobiology of disease Vol. 209; p. 106904
• Main Authors: Tan, Hong, Hu, Yu-Ting, Goudswaard, Alyssa, Li, Yong-Jian, Balesar, Rawien, Swaab, Dick, Bao, Ai-Min
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2025; Elsevier
• Subjects: Adult; Aged; Arginine vasopressin; Arginine Vasopressin - metabolism; Bipolar disorder; Bipolar Disorder - metabolism; Bipolar Disorder - pathology; Cohort Studies; Depressive Disorder, Major - metabolism; Female; Humans; Major depressive disorder; Male; Middle Aged; Oxytocin; Oxytocin - metabolism; Paraventricular Hypothalamic Nucleus - metabolism; Paraventricular nucleus; Supraoptic nucleus; Supraoptic Nucleus - metabolism; Vasopressins - metabolism; Bipolar disorder; Paraventricular nucleus; Oxytocin; Arginine vasopressin; Major depressive disorder; Supraoptic nucleus
• ISSN: 0969-9961; 1095-953X; 1095-953X
• DOI: 10.1016/j.nbd.2025.106904

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 (OTPVN) 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 (OTSON). 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 OTPVN-ir but relatively stable AVPPVN-ir in male BD, and a significantly decreased AVPPVN-ir but relatively stable OTPVN-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 OTPVN-ir was found in male BD.•Decreased vasopressin AVPPVN-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