Multiple sclerosis (MS) patients have high levels of cortisol, a stress hormone, compared to healthy controls. Also, patients categorized as non-cognitive fatigue show a higher variability in cortisol levels and perform worse on an attention task.
Those findings are documented in the study, “Relation between cognitive fatigue and circadian or stress related cortisol levels in MS patients,” published in the journal Multiple Sclerosis and Related Disorders.
The inflammation that characterizes MS is triggered by an imbalance of cytokines, small proteins that regulate the immune system.
Cytokines also stimulate specific brain regions, particularly at the hypothalamic-pituitary-adrenal (HPA) axis, to produce adrenocorticotropic hormone (ACTH), which regulates the levels of cortisol. The HPA is a key network within the neuroendocrine system that regulates stress, digestion, immune responses, mood and emotions.
Previous studies have reported that the HPA axis is hyper-activated in MS patients, who also show elevated levels of stress hormone cortisol. Additional studies also suggest that an imbalance of the HPA axis is linked to depression and chronic fatigue.
Fatigue, defined as a lack of drive and energy and a chronic feeling of tiredness, is a common symptom of MS. Yet, it remains unclear whether cortisol levels are linked to fatigue in MS.
Researchers in Germany and the Netherlands now investigated how cortisol levels change during the day and in response to fatigue in MS patients.
In total, the team analyzed 20 healthy controls and 40 MS patients, including 27 experiencing fatigue. Fatigued patients scored 28 or higher on the fatigue scale for motor and cognitive functions (MSFC).
Cortisol levels were measured in saliva at four different times — in the morning and afternoon, and before and after running a cognitively demanding attention task. The task, adapted from the test battery for attentional performance (TAP, Version 1.7), demanded participant’s visual and hearing attention and were divided into five blocks of about four minutes each.
The level of cognitive fatigue was measured with the visual analogue scale (VAS) after asking participants to rate their fatigue on a scale of zero to 100.
As expected, cortisol levels were higher in the morning than in the afternoon for the three groups of participants (healthy controls, non-fatigue MS patients, and fatigue MS patients). Cortisol levels significantly decreased between the morning and the afternoon in all groups, “reflecting the typical morning peak of the circadian cortisol fluctuation,” researchers wrote.
In both MS groups there was no association between age, disability (as measured by the expanded disability status scale, EDSS), use of immunomodulatory therapies, and cortisol levels. Furthermore, no correlation was seen between cortisol levels and a diagnosis of relapsing-remitting MS or secondary progressive MS.
Overall, MS patients had significantly higher cortisol levels at the first measure (before the reaction time task) in both the morning and afternoon compared to the healthy control group.
The reaction time on the cognitive task was not correlated with cortisol levels. The VAS scores used to assess fatigue correlated with cortisol levels before the cognitive task.
Fatigue MS patients, as expected, showed higher levels of fatigue and depression than non-fatigue patients. However, they did not show a task-related performance decline.
The non-fatigue MS group performed worse in cognitive tests in the morning and afternoon compared to controls. This group also showed greater cortisol level changes than the other two groups.
Healthy controls were better than fatigue MS patients in cognitive tests, but only in the first test block. On the fifth test block in the morning, non-fatigue patients made significantly more omissions on the attention task than the fatigue group (six vs. one).
Fatigue MS patients had significantly slower reaction times than healthy controls in both afternoon blocks — median of the first block 664 vs. 620 milliseconds in controls, and median of the last block 658 vs. 620 milliseconds. Non-fatigue MS patients also performed worse than controls on the last block in the afternoon (679 vs. 620 milliseconds). No significant differences in response time were found between MS groups.
The team suggests several hypothesis to explain the findings. One is that non-fatigue MS patients experienced high cortisol levels due to the loss of myelin (the hallmark of MS) in the brain stem, a brain structure that helps control cortisol production. Lesions in this region also may explain why these patients had not experienced fatigue.
Overall, the results show that MS patients have increased levels of cortisol.
More studies, however, are needed to better understand the link between MS, cortisol levels and fatigue, they added.
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