Kang et al. (2026)
- Authors: Hailan Kang, Tianrui Shao, Yuqing Shi, Shilei Wang, Huazhong Xiong, Xuanyan Jin, Jixiang Ren
- Institutes: School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China, Institute of Brain Science, Beijing University of Chinese Medicine, Beijing, China
- Publisher: Frontiers in Neuroscience
- Link: DOI
Summary
This review provides a comprehensive theoretical framework for understanding ‘brain fog’ by linking systemic stress responses to physical changes in the brain’s memory center. It shifts the focus toward the hippocampus as a key site of injury, suggesting that cognitive symptoms in ME/CFS are not merely subjective but may stem from measurable neurobiological dysregulation. For patients, this validates the physiological basis of their cognitive struggles and points toward HPA axis regulation as a potential path for future therapies. The evidence level is a high-level theoretical synthesis of existing literature rather than a new clinical trial.
What was researched?
This review explored how chronic stress and the resulting dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis contribute to cognitive dysfunction, commonly known as ‘brain fog,’ in ME/CFS patients.
Why was it researched?
Cognitive symptoms like impaired memory and attention are highly disabling in ME/CFS, yet the exact neurobiological mechanisms connecting stress, hormones, and brain function remain poorly understood.
How was it researched?
The researchers conducted a comprehensive literature review to synthesize current evidence on HPA axis activity, hippocampal plasticity, neuroinflammation, and oxidative stress specifically within the context of ME/CFS.
What has been found?
The study found that prolonged stress leads to altered cortisol rhythmicity and impaired negative feedback, which triggers neuroinflammatory responses and oxidative stress. These processes appear to disrupt hippocampal plasticity, including reduced neurogenesis and impaired synaptic integrity, leading to deficits in learning and memory. Furthermore, disturbances in neurotransmitter homeostasis were identified as significant contributors to the observed cognitive decline.
Discussion
A major strength of this review is its integration of multisystemic factors, though it acknowledges that the direct causal relationship between specific HPA axis abnormalities and hippocampal structural changes in ME/CFS requires further longitudinal imaging studies. The complexity of hormonal patterns in patients remains a challenge for standardized diagnostics.
Conclusion & Future Work
The authors conclude that targeting HPA axis dysregulation and restoring hippocampal plasticity offer promising avenues for treating cognitive dysfunction in ME/CFS. Future research should focus on identifying specific biomarkers to guide these interventions.