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Review
. 2023 Jul:163:114852.
doi: 10.1016/j.biopha.2023.114852. Epub 2023 May 8.

Intertwined associations between oxytocin, immune system and major depressive disorder

Junliang Jiang  1 , Miaoxian Yang  2 , Mi Tian  2 , Zhong Chen  3 , Lei Xiao  4 , Ye Gong  5
Affiliations
Review

Intertwined associations between oxytocin, immune system and major depressive disorder

Junliang Jiang et al. Biomed Pharmacother. 2023 Jul.

Abstract

Major depressive disorder (MDD) is a prominent psychiatric disorder with a high prevalence rate. The recent COVID-19 pandemic has exacerbated the already high prevalence of MDD. Unfortunately, a significant proportion of patients are unresponsive to conventional treatments, necessitating the exploration of novel therapeutic strategies. Oxytocin, an endogenous neuropeptide, has emerged as a promising candidate with anxiolytic and antidepressant properties. Oxytocin has been shown to alleviate emotional disorders by modulating the hypothalamic-pituitary-adrenal (HPA) axis and the central immune system. The dysfunction of the immune system has been strongly linked to the onset and progression of depression. The central immune system is believed to be a key target of oxytocin in ameliorating emotional disorders. In this review, we examine the evidence regarding the interactions between oxytocin, the immune system, and depressive disorder. Moreover, we summarize and speculate on the potential roles of the intertwined association between oxytocin and the central immune system in treating emotional disorders.

Keywords: Depression; HPA axis; Immune system; Inflammation; Oxytocin.

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Conflict of interest statement

Declaration of Competing Interest We declare that we have no financial and personal relationships with other people organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled.

Figures

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Graphical abstract
Fig. 1
Fig. 1
Stress-HPA axis-immune crosstalk in depression. Hypothalamus neurons will be activated by stressful stimuli to release CRH and vasopressin. These hormones jointly promote the ACTH release from the anterior pituitary, and ACTH further acts on the adrenal gland to promote cortisol release. Excessive cortisol could disturb the homeostasis of the HPA axis, resulting in the immune dysfunction, including elevations of inflammation cytokines and BBB impairment. Then, these inflammation cytokines could cross through the damaged BBB into CNS. Inflammation cytokines and immune signal would activate central microglia and astrocyte to release inflammation cytokine, leading to a vicious circle. All of these damage factors will lead to the neuro dysfunction, result in depression. Solid red arrows represent activation, while dotted red arrows indicate passing through BBB.
Fig. 2
Fig. 2
Interaction between OXT signal and immune system in anti-depression. Stress will activate OXT neurons in PVN and SON to produce endogenous OXT. Some OXT can be released via volume transmission or axonal projection to the PFC, VTA, HIP, BLA. Some OXT can be released into periphery circulation via posterior pituitary. Endogenous or exogenous OXT targets OXTR expressed in HPA axis and immune cells to suppress abnormal immune response, resulting in improvement of depressive symptoms. Purple arrow represents OXT alleviating depression via immune system. Black blunt arrow represents the inhibition effect.
See this image and copyright information in PMC

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