Chronic psychological stress can worsen myasthenia gravis (MG) symptoms by overactivating the body’s central stress hormone pathway, according to a new study done in mice. The findings may help explain why many patients notice their symptoms flare during stressful periods.
The study, published in Psychoneuroendocrinology, found that mice with both MG and chronic stress developed more severe muscle weakness than mice with MG alone. The effect was tied to overactivation of the hypothalamic-pituitary-adrenal (HPA) axis, the hormonal system that governs the body’s stress response.
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The researchers compared three groups of mice: one with MG, one exposed to chronic stress and one with both MG and stress. To create the disease model, known as experimental autoimmune myasthenia gravis, they injected mice with a fragment of the acetylcholine receptor (AChR), a protein on muscle cells that receives nerve signals. That injection and two boosters led the animals’ immune systems to attack these receptors, mimicking actual MG.
The stressed groups faced six weeks of varied, unpredictable mild stressors. To confirm the stress took hold, the researchers used two standard tests to analyze their behavior before and after the six weeks. They found that after the six weeks, the stressed mice spent less time in the open center of an enclosure (a measure of anxiety) and drank less sweetened water (a measure of depression-like behavior).
Stressed mice with MG lost significantly more grip strength than mice with MG alone. They also showed a larger drop in time spent in the open center of the enclosure than mice under stress alone, indicating increased anxiety-like behavior in the dual-disease group. That fits with patient research estimating anxiety affects 20% to 40% of people with MG and depression 20% to 30%; one study of 155 patients linked depression to returning MG symptoms.
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The stressed MG mice also had much higher blood cortisol levels, the primary stress hormone, and a shift in immune cell balance: more Th17 cells, which promote inflammation, and fewer regulatory T cells, which normally keep the immune system in check. Two inflammatory proteins, TNF-alpha and IL-6, were also elevated, and their muscle and thymus tissue showed more signs of inflammation.
The researchers also tested two drugs that act on the central stress-hormone pathway. The first, RU486 (mifepristone), directly blocks cortisol from reaching its receptors. In stressed mice with MG, it sharply lowered cortisol levels, significantly improved grip strength and reduced inflammatory T cell populations.
The other drug, paroxetine, is a selective serotonin reuptake inhibitor (SSRI), an antidepressant that works indirectly by altering mood-regulating signals in the brain. It reduced one inflammatory cell type but did not significantly improve grip strength or lower cortisol.
“This study demonstrates for the first time that chronic stress worsens the pathological process of MG through the HPA-immune axis, highlighting the need for clinical attention to the psychological management of patients with MG,” the study’s authors wrote.
However, the authors cautioned that the findings come from an animal model and require further research in people with MG.
