Lei Ai Ai, Phang Vanessa Wen Xian, Lee Yu Zhao, Kow Audrey Siew Foong, Tham Chau Ling, Ho Yu-Cheng, Lee Ming Tatt
Faculty of Pharmaceutical Sciences, UCSI University, Kuala Lumpur 56000, Malaysia.
Faculty of Medicine and Health Sciences, UCSI University, Kuala Lumpur 56000, Malaysia.
Int J Mol Sci. 2025 Mar 24;26(7):2940. doi: 10.3390/ijms26072940.
Chronic stress significantly contributes to the development of depressive disorders, with the hypothalamic-pituitary-adrenal (HPA) axis playing a central role in mediating stress responses. This review examines the neurobiological alterations in the hippocampus linked to HPA axis dysregulation in chronic stress-associated depressive disorders. The prolonged activation of the HPA axis disrupts cortisol regulation, leading to the decline of both physical and mental health. The chronic stress-induced HPA axis dysfunction interacts with inflammatory pathways and generates oxidative stress, contributing to cellular damage and neuroinflammation that further aggravates depressive symptoms. These processes result in structural and functional alterations in the hippocampus, which is essential for emotional regulation and cognitive function. Comprehending the impact of chronic stress on the HPA axis and associated neurobiological pathways is essential for formulating effective interventions for depressive disorders. This review summarises the existing findings and underscores the necessity for future investigations into intervention strategies to improve physical and psychological wellbeing targeting at HPA axis dysregulation for the betterment of psychological wellbeing and human health.
慢性应激对抑郁症的发展有显著影响，下丘脑-垂体-肾上腺（HPA）轴在介导应激反应中起核心作用。本综述探讨了与慢性应激相关抑郁症中HPA轴失调相关的海马体神经生物学改变。HPA轴的长期激活会破坏皮质醇调节，导致身心健康下降。慢性应激诱导的HPA轴功能障碍与炎症途径相互作用并产生氧化应激，导致细胞损伤和神经炎症，进一步加重抑郁症状。这些过程导致海马体的结构和功能改变，而海马体对情绪调节和认知功能至关重要。了解慢性应激对HPA轴及相关神经生物学途径的影响对于制定有效的抑郁症干预措施至关重要。本综述总结了现有研究结果，并强调了未来针对HPA轴失调改善身心健康的干预策略研究的必要性，以促进心理健康和人类健康。
