Abstract
The hypothalamic-pituitary-adrenal (HPA) axis is involved in the pathophysiology of many neuropsychiatric disorders. Increased HPA axis activity can be observed during chronic stress, which plays a key role in the pathophysiology of depression. Overactivity of the HPA axis occurs in major depressive disorder (MDD), leading to cognitive dysfunction and reduced mood. There is also a correlation between the HPA axis activation and gut microbiota, which has a significant impact on the development of MDD. It is believed that the gut microbiota can influence the HPA axis function through the activity of cytokines, prostaglandins, or bacterial antigens of various microbial species. The activity of the HPA axis in schizophrenia varies and depends mainly on the severity of the disease. This review summarizes the involvement of the HPA axis in the pathogenesis of neuropsychiatric disorders, focusing on major depression and schizophrenia, and highlights a possible correlation between these conditions. Although many effective antidepressants are available, a large proportion of patients do not respond to initial treatment. This review also discusses new therapeutic strategies that affect the HPA axis, such as glucocorticoid receptor (GR) antagonists, vasopressin V1B receptor antagonists and non-psychoactive CB1 receptor agonists in depression and/or schizophrenia.
Highlights
The hypothalamic-pituitary-adrenal (HPA) axis plays an important role in the body’s adaptation to stressful situations [1,2]
The normalization of the HPA axis activity in patients with depression may prove to be an effective target of pharmacotherapy and understanding the exact mechanisms of their synergistic action may contribute to the development of new therapeutic strategies for this disease [3]
Chronic stress plays a large role in the development of depressive disorders and it is involved in elevated cortisol levels, which is largely due to dysregulation of the HPA axis [37,38,39]
Summary
The hypothalamic-pituitary-adrenal (HPA) axis plays an important role in the body’s adaptation to stressful situations [1,2]. Childhood traumatic events related to stress factors significantly increase the risk of mental illness in adulthood. The mechanism of this phenomenon is based, among others, on HPA axis dysfunction. The normalization of the HPA axis activity in patients with depression may prove to be an effective target of pharmacotherapy and understanding the exact mechanisms of their synergistic action may contribute to the development of new therapeutic strategies for this disease [3]. An imbalance between the antioxidant defense system (AODS) and the production of reactive oxygen species (ROS) leads to oxidative stress An imbalance between these systems is observed in psychotic disorders, such as schizophrenia [6]. Exploring new mechanisms of disease onset may enhance personalized therapy and represents a potential target for future research theories [4,5,6]
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