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Review
. 2023 Nov 29;12(23):2726.
doi: 10.3390/cells12232726.

The Role of Cortisol in Chronic Stress, Neurodegenerative Diseases, and Psychological Disorders

Emilija Knezevic  1   2 , Katarina Nenic  1   3 , Vladislav Milanovic  1   4 , Nebojsa Nick Knezevic  1   5   6
Affiliations
Review

The Role of Cortisol in Chronic Stress, Neurodegenerative Diseases, and Psychological Disorders

Emilija Knezevic et al. Cells. .

Abstract

Cortisol, a critical glucocorticoid hormone produced by the adrenal glands, plays a pivotal role in various physiological processes. Its release is finely orchestrated by the suprachiasmatic nucleus, governing the circadian rhythm and activating the intricate hypothalamic-pituitary-adrenal (HPA) axis, a vital neuroendocrine system responsible for stress response and maintaining homeostasis. Disruptions in cortisol regulation due to chronic stress, disease, and aging have profound implications for multiple bodily systems. Animal models have been instrumental in elucidating these complex cortisol dynamics during stress, shedding light on the interplay between physiological, neuroendocrine, and immune factors in the stress response. These models have also revealed the impact of various stressors, including social hierarchies, highlighting the role of social factors in cortisol regulation. Moreover, chronic stress is closely linked to the progression of neurodegenerative diseases, like Alzheimer's and Parkinson's, driven by excessive cortisol production and HPA axis dysregulation, along with neuroinflammation in the central nervous system. The relationship between cortisol dysregulation and major depressive disorder is complex, characterized by HPA axis hyperactivity and chronic inflammation. Lastly, chronic pain is associated with abnormal cortisol patterns that heighten pain sensitivity and susceptibility. Understanding these multifaceted mechanisms and their effects is essential, as they offer insights into potential interventions to mitigate the detrimental consequences of chronic stress and cortisol dysregulation in these conditions.

Keywords: chronic stress; cortisol; hypothalamic–pituitary–adrenal (HPA) axis; neuroinflammation; physiological processes.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Proposed interplay between the CNS, endocrine, and immune systems.
Figure 2
Figure 2
Feedback loop of hippocampal atrophy, overactive HPA axis, and GC hypersecretion.
Figure 3
Figure 3
Model for the potential mechanism of cortisol dysregulation implication in PD.
Figure 4
Figure 4
Chronic stress mechanism and implications.
See this image and copyright information in PMC

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