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 paraventricula...
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| Published in | Neurobiology of disease Vol. 209; p. 106904 |
|---|---|
| Main Authors | , , , , , , |
| Format | Journal Article |
| Language | English |
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United States
Elsevier Inc
01.06.2025
Elsevier |
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| Online Access | Get full text |
| ISSN | 0969-9961 1095-953X 1095-953X |
| DOI | 10.1016/j.nbd.2025.106904 |
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| 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 (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 |
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| AbstractList | 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) 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 ) 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 ). 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 -ir but relatively stable AVP -ir in male BD, and a significantly decreased AVP -ir but relatively stable OT -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) 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) 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) 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 |
| ArticleNumber | 106904 |
| Author | Hu, Yu-Ting Balesar, Rawien Li, Yong-Jian Bao, Ai-Min Goudswaard, Alyssa Tan, Hong Swaab, Dick |
| Author_xml | – sequence: 1 givenname: Hong surname: Tan fullname: Tan, Hong organization: Department of Neurobiology and Department of Neurology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China – sequence: 2 givenname: Yu-Ting surname: Hu fullname: Hu, Yu-Ting organization: Center for Basic and Translational Research of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China – sequence: 3 givenname: Alyssa surname: Goudswaard fullname: Goudswaard, Alyssa organization: Netherlands Institute for Neuroscience, an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, BA, the Netherlands – sequence: 4 givenname: Yong-Jian surname: Li fullname: Li, Yong-Jian organization: NHC and CAMS key laboratory of Medical Neurobiology, Zhejiang University School of Brain Science and Brain Medicine, Hangzhou, China – sequence: 5 givenname: Rawien surname: Balesar fullname: Balesar, Rawien organization: Netherlands Institute for Neuroscience, an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, BA, the Netherlands – sequence: 6 givenname: Dick surname: Swaab fullname: Swaab, Dick email: d.swaab@nin.knaw.nl organization: Netherlands Institute for Neuroscience, an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, BA, the Netherlands – sequence: 7 givenname: Ai-Min surname: Bao fullname: Bao, Ai-Min email: baoaimin@zju.edu.cn organization: Department of Neurobiology and Department of Neurology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/40204168$$D View this record in MEDLINE/PubMed |
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| Keywords | Bipolar disorder Paraventricular nucleus Oxytocin Arginine vasopressin Major depressive disorder Supraoptic nucleus |
| Language | English |
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