Multiple sclerosis: more stress = more relapses?
Stress can promote relapses and disability progression through excessive inflammatory reactions and an increased tendency to degeneration.
An increasing number of studies have documented a link between stressful life events and an increased risk of developing MS and, in particular, a higher relapse rate.1,2 A study from the University of Pittsburgh reported that stressful events, such as the death of a relative or a divorce, were followed by a relapse within six weeks in 50% of cases.3 Another study from the Netherlands also found that stressful life events more than doubled the relapse rate in the following four weeks. Emotional states of emergency, which are actually positive, can also represent such stress. After major stresses, the likelihood of developing a new MRI lesion in the next eight weeks was about 1.6 times higher, according to data from the USA.3,4
Key takeaways
- Stress has been linked to autoimmune diseases by numerous studies, as it contributes to the dysregulation of immune signalling pathways1
- Numerous data point to the link between stressful circumstances - especially prolonged emotional stress, conflict, loss, lack of social support, anxiety and depression - and exacerbations of MS1,2
How life events influence the development of MS
The mechanisms by which stress stimulates inflammatory activity are still only partially understood. In addition to autonomic tone and stress reactivity, it may be important that stress leads to the release of corticotropin-releasing hormone (CRH) and neurotensin, which can increase the activation of microglia and mast cells.1,5 The subsequent damage to the blood-brain barrier may be crucial for the migration of self-reactive T cells and the initiation of the autoimmune process that leads to the formation of new lesions.2
Experimental work also suggests that prolonged stress impairs communication between the neuroendocrine system and the immune system and can lead to steroid resistance. Stress activates the hypothalamic-pituitary-adrenal axis, which promotes the release of corticosterone. This normally suppresses pathogenic stimulation of the immune system. Under chronic stress, the experimental animals became less responsive to the immunosuppressive effects of corticosterone over time (especially to proinflammatory T cell lines) and thus developed a higher risk of destructive autoimmunity.6
But acute stress also shifts the balance from Th2 (or anti-inflammatory) to Th1 (or pro-inflammatory) cytokines. Even in healthy people, for example, the state exam was associated with a significant increase in TNF-alpha; this cytokine has been shown to be elevated in MS relapses.3
Stress management techniques, such as mindfulness and relaxation exercises, correlated with reduced inflammatory activity in studies and should therefore be a key component of therapy. More on this in Part 2.
- Giordano, A. et al. Stress related to COVID-19 pandemic as a trigger for disease activity in multiple sclerosis: a case report. Neurol Sci 42, 3969–3971 (2021).
- Artemiadis, A. K., Anagnostouli, M. C. & Alexopoulos, E. C. Stress as a risk factor for multiple sclerosis onset or relapse: a systematic review. Neuroepidemiology 36, 109–120 (2011).
- Stress and MS | Overcoming Multiple Sclerosis. https://overcomingms.org/about-multiple-sclerosis/ms-encyclopedia/stress-and-ms.
- Lovera, J. & Reza, T. Stress in multiple sclerosis: review of new developments and future directions. Curr Neurol Neurosci Rep 13, 398 (2013).
- Mohr, D. C. & Pelletier, D. A temporal framework for understanding the effects of stressful life events on inflammation in patients with multiple sclerosis. Brain Behav Immun 20, 27–36 (2006).
- Harpaz, I. et al. Chronic exposure to stress predisposes to higher autoimmune susceptibility in C57BL/6 mice: Glucocorticoids as a double-edged sword. European Journal of Immunology 43, 758–769 (2013).