A consistent association between stressful life events and subsequent exacerbation in multiple sclerosis (MS) has been found by investigators from the University of California, San Francisco. Although many possible triggers of exacerbation have been proposed, the researchers acknowledged the role of stressful life events as controversial.

More accurately, it is nontraumatic stressful life events that may cause the exacerbations—an important distinction—the team noted. Nontraumatic stressful life events include job difficulties or financial problems.

The researchers cited a previous study that examined the effects of a traumatic, life-threatening stressor and found that such a stressor reduced the risk of exacerbation. “These findings raise the important hypothesis that different types of stressors may have different effects,” according to the investigators.

THE NEGATIVE AND POSITIVE

The researchers conducted a meta-analysis of 14 empirical studies that met the inclusion criteria of using standardized diagnostic criteria to evaluate and quantify MS, neurologic-confirmed exacerbation, standard checklist methods to measure stressful life events, case-control or longitudinal design, and providing enough information about results to allow the investigators to compute an estimate of effect size.

The study indicated stress is related to exacerbation of MS with a clinically meaningful weighted average effect size greater than the benefit of the principal class of disease-modifying drugs used to treat the disease. Although the comparison was not meant to question the use of the drugs, “We suggest that the negative effects of stress on exacerbation of MS are at least as great as the positive effects of a class of drugs widely considered to produce clinically meaningful results,” the authors stated.

POTENTIAL MECHANISMS

The study, which appeared in the March 27 BMJ, reviewed a number of theories as to the mechanisms behind exacerbations, citing studies that have shown that reducing distress in those with MS can reduce T-cell production of gamma interferon, a proinflammatory cytokine suspected to be vital in the pathogenesis of exacerbation. The investigators allowed that “no biological mechanism linking stress or distress and inflammatory processes in MS has been tested.”

Animal studies have demonstrated that even small increases of cortisol concentrations, similar to the concentrations seen in nontraumatic stress, enhance the sensitivity of T cells to a number of cytokines and peptides that promote a proinflammatory response, the researchers said. Conversely, sustained increases of cortisol levels have also been shown to increase the risk of inflammation. Mast cells activated by increases in corticotropin–releasing factor related to stress increase the permeability of the blood-brain barrier and increase inflammation through the release of various agents. The authors also observed that “While these potential mechanisms are intriguing, none has been adequately tested among patients with MS.”

NO BLAME

It was noted that although the findings show a significant association between stress and exacerbation, the effect size is modest, and the association is not consistent across patients or even individual patients across time. These data do not allow the linking of specific stressors to exacerbations, nor should they be “misconstrued to suggest that patients with MS bear any responsibility for exacerbations,” cautioned the researchers.

NR

—Heidi W. Moore

Suggested Reading
Mohr DC, Hart SL, Julian L, et al. Association between stressful life events and exacerbation in multiple sclerosis: a meta-analysis. BMJ. 2004;328:731-733.
Nisipeanu P, Korczyn AD. Psychological stress as risk factor for exacerbations in multiple sclerosis. Neurology. 1993;43:1311-1312.

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