Different oxytocin and corticotropin-releasing hormone system changes in bipolar disorder and major depressive disorder patients
Lei Guo,
Yang-Jian Qi,
Hong Tan,
Dan Dai,
Rawien Balesar,
Arja Sluiter,
Joop van Heerikhuize,
Shao-Hua Hu,
Dick F. Swaab,
Ai-Min Bao
Affiliations
Lei Guo
Department of Neurobiology and Department of Neurology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; NHC and CAMS key laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Research and Brain-Machine Integration, School of Brain Science and Brain Medicine, Zhejiang University, China
Yang-Jian Qi
Department of Neurobiology and Department of Neurology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; NHC and CAMS key laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Research and Brain-Machine Integration, School of Brain Science and Brain Medicine, Zhejiang University, China
Hong Tan
Department of Neurobiology and Department of Neurology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
Dan Dai
Department of Neurobiology and Department of Neurology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; NHC and CAMS key laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Research and Brain-Machine Integration, School of Brain Science and Brain Medicine, Zhejiang University, China
Rawien Balesar
Netherlands Institute for Neuroscience, an Institute of the Royal Netherlands Academy of Arts and Sciences, KNAW, Meibergdreef 47, 1105 BA Amsterdam, the Netherlands
Arja Sluiter
Netherlands Institute for Neuroscience, an Institute of the Royal Netherlands Academy of Arts and Sciences, KNAW, Meibergdreef 47, 1105 BA Amsterdam, the Netherlands
Joop van Heerikhuize
Netherlands Institute for Neuroscience, an Institute of the Royal Netherlands Academy of Arts and Sciences, KNAW, Meibergdreef 47, 1105 BA Amsterdam, the Netherlands
Shao-Hua Hu
Department of Mental Health, Zhejiang Province Key Laboratory of Mental Disorder's Management, First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qing Chun Road, Hangzhou 310003, China
Dick F. Swaab
Department of Neurobiology and Department of Neurology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; NHC and CAMS key laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Research and Brain-Machine Integration, School of Brain Science and Brain Medicine, Zhejiang University, China; Netherlands Institute for Neuroscience, an Institute of the Royal Netherlands Academy of Arts and Sciences, KNAW, Meibergdreef 47, 1105 BA Amsterdam, the Netherlands; Corresponding author at: Prof. of Neurobiology, University of Amsterdam, Netherlands Institute for Neuroscience, KNAW, Meibergdreef 47, 1105 BA Amsterdam, the Netherlands.
Ai-Min Bao
Department of Neurobiology and Department of Neurology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; NHC and CAMS key laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Research and Brain-Machine Integration, School of Brain Science and Brain Medicine, Zhejiang University, China; Corresponding author at: Prof. of Neurobiology, Department of Neurobiology and Department of Neurology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China.
Summary: Background: Oxytocin (OXT) and corticotropin-releasing hormone (CRH) are both produced in hypothalamic paraventricular nucleus (PVN). Central CRH may cause depression-like symptoms, while peripheral higher OXT plasma levels were proposed to be a trait marker for bipolar disorder (BD). We aimed to investigate differential OXT and CRH expression in the PVN and their receptors in prefrontal cortex of major depressive disorder (MDD) and BD patients. In addition, we investigated mood-related changes by stimulating PVN-OXT in mice. Methods: Quantitative immunocytochemistry and in situ hybridization were performed in the PVN for OXT and CRH on 6 BD and 6 BD-controls, 9 MDD and 9 MDD-controls. mRNA expressions of their receptors (OXTR, CRHR1 and CRHR2) were determined in anterior cingulate cortex and dorsolateral prefrontal cortex (DLPFC) of 30 BD and 34 BD-controls, and 24 MDD and 12 MDD-controls. PVN of 41 OXT-cre mice was short- or long-term activated by chemogenetics, and mood-related behavior was compared with 26 controls. Findings: Significantly increased OXT-immunoreactivity (ir), OXT-mRNA in PVN and increased OXTR-mRNA in DLPFC, together with increased ratios of OXT-ir/CRH-ir and OXTR-mRNA/CRHR-mRNA were observed in BD, at least in male BD patients, but not in MDD patients. PVN-OXT stimulation induced depression-like behaviors in male mice, and mixed depression/mania-like behaviors in female mice in a time-dependent way. Interpretation: Increased PVN-OXT and DLPFC-OXTR expression are characteristic for BD, at least for male BD patients. Stimulation of PVN-OXT neurons induced mood changes in mice, in a pattern different from BD. Funding: National Natural Science Foundation of China (81971268, 82101592).
