Zhang Y, Wang S, Hei MY. Attenuating neuropsychiatric disorders of early-life stress: The protective role of oxytocin. World J Psychiatry 2026; 16(4): 115109 [DOI: 10.5498/wjp.v16.i4.115109]
Corresponding Author of This Article
Ming-Yan Hei, MD, Professor, Neonatal Center, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, No. 56 Nanlishi Road, Xicheng District, Beijing 100045, China. heimingyan@bch.com.cn
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Psychiatry
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Apr 19, 2026 (publication date) through Mar 30, 2026
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World Journal of Psychiatry
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2220-3206
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Zhang Y, Wang S, Hei MY. Attenuating neuropsychiatric disorders of early-life stress: The protective role of oxytocin. World J Psychiatry 2026; 16(4): 115109 [DOI: 10.5498/wjp.v16.i4.115109]
World J Psychiatry. Apr 19, 2026; 16(4): 115109 Published online Apr 19, 2026. doi: 10.5498/wjp.v16.i4.115109
Attenuating neuropsychiatric disorders of early-life stress: The protective role of oxytocin
Yuan Zhang, Shu Wang, Ming-Yan Hei
Yuan Zhang, Ming-Yan Hei, Neonatal Center, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing 100045, China
Shu Wang, Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China
Co-corresponding authors: Shu Wang and Ming-Yan Hei.
Author contributions: Zhang Y collected the data, analyzed the data, drafted the manuscript, and revised the manuscript; Wang S designed the study, collected and analyzed the data, drafted the manuscript, and revised the manuscript; Hei MY designed the study, collected the data, analyzed the data, and revised the manuscript. All the authors read and approved the final manuscript. Wang S and Hei MY contributed equally to this work as co-corresponding authors. Hei MY was instrumental and responsible for data re-analysis and re-interpretation, comprehensive literature search, preparation and submission of the current version of the manuscript with a new focus on proposing future directions and clinical implications of the protective role of oxytocin in neuropsychiatric disorders of early-life stress. She also supervised the whole process of the project. Wang S conceptualized, designed, and analyzed data for this study. He searched the literature, revised and finished the early version of the manuscript with the focus on neurobiological mechanisms of early-life stress and oxytocin intervention, as well as translational evidence from preclinical and human studies. This collaboration between Hei MY and Wang S is crucial for the publication of this manuscript and other manuscripts still in preparation.
Conflict-of-interest statement: The authors declare that they have no conflicts of interest.
Corresponding author: Ming-Yan Hei, MD, Professor, Neonatal Center, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, No. 56 Nanlishi Road, Xicheng District, Beijing 100045, China. heimingyan@bch.com.cn
Received: October 9, 2025 Revised: November 20, 2025 Accepted: December 23, 2025 Published online: April 19, 2026 Processing time: 173 Days and 12.5 Hours
Abstract
Early-life stress (ELS) constitutes a significant risk factor for the development of neuropsychiatric disorders, including depression, anxiety, and schizophrenia, through its enduring impact on neural circuitry, endocrine function, and epigenetic regulation. Despite advances in understanding the mechanisms underlying ELS-induced psychopathology, effective interventions remain limited. This review examines the emerging evidence supporting oxytocin as a promising therapeutic agent for mitigating the long-term consequences of ELS. Oxytocin, a neuropeptide integral to social bonding and stress regulation, demonstrates robust neuroprotective and resilience-promoting properties across preclinical and clinical studies. In animal models of ELS, oxytocin administration during critical developmental windows rescues deficits in amygdala-prefrontal connectivity, normalizes hypothalamic-pituitary-adrenal axis hyperactivity, and enhances hippocampal neurogenesis. Human studies further indicate that intranasal oxytocin modulates limbic reactivity to social threat and improves socioemotional functioning in individuals with histories of childhood trauma. Mechanistically, oxytocin may reverse ELS-associated epigenetic modifications and attenuate neuroinflammatory pathways, thereby restoring neuroendocrine and immune homeostasis. However, important questions remain regarding optimal dosing, timing, sex-specific responses, and long-term safety. This review synthesizes evidence from molecular, systems, and behavioral neuroscience to highlight oxytocin’s dual role as both a corrective agent for maladaptive neural changes and a facilitator of resilience. Future research directions include the development of targeted oxytocin delivery systems, identification of predictive biomarkers, and integration with psychosocial interventions to maximize therapeutic efficacy. Addressing these challenges may contribute for precision medicine approaches to alleviate the intergenerational burden of early adversity.
Core Tip: Early-life stress increases lifelong risk for neuropsychiatric disorders via lasting neural, endocrine, and epigenetic changes. Oxytocin, a key neuropeptide, shows promise in mitigating these effects by normalizing amygdala-prefrontal connectivity, reducing hypothalamic-pituitary-adrenal axis hyperactivity, promoting hippocampal neurogenesis, and reversing stress-associated epigenetic marks. However, its efficacy is context-dependent and influenced by factors like sex, timing, and administration route. Future oxytocin-based therapies should be integrated with psychosocial support and tailored through a precision medicine framework to effectively promote resilience in the affected individuals.
