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Association between stressful life events and exacerbation in multiple sclerosis: a meta-analysis

BMJ 2004; 328 doi: (Published 25 March 2004) Cite this as: BMJ 2004;328:731
  1. David C Mohr (dmohr{at}, associate professor1,
  2. Stacey L Hart, assistant professor1,
  3. Laura Julian, postdoctoral fellow2,
  4. Darcy Cox, assistant professor3,
  5. Daniel Pelletier, assistant professor3
  1. 1Department of Psychiatry, University of California, San Francisco, CA 94142, USA
  2. 2Department of Medicine, University of California, San Francisco
  3. 3Department of Neurology, University of California, San Francisco
  1. Correspondence to: D Mohr
  • Accepted 22 January 2004


Objective To quantify the association between stressful life events and exacerbations of multiple sclerosis.

Data sources PubMed, PsychInfo, and Psychological Abstracts searched for empirical papers from 1965 to February 2003 with terms “stress”, “trauma”, and “multiple sclerosis”.

Review methods Three investigators independently reviewed papers for inclusion/exclusion criteria and extracted the relevant data, including methods, sample statistics, and outcomes.

Results Of 20 studies identified, 14 were included. The meta-analysis showed a significant increase in risk of exacerbation in multiple sclerosis after stressful life events, with a weighted average effect size of d = 0.53 (95% confidence interval 0.40 to 0.65), P < 0.0001. The studies were homogenous, q = 16.62, p = 0.22, i2 = 21.8%. Neither sampling nor study methods had any effect on study outcomes.

Conclusions There is a consistent association between stressful life events and subsequent exacerbation in multiple sclerosis. However these data do not allow the linking of specific stressors to exacerbations nor should they be used to infer that patients are responsible for their exacerbations. Investigation of the psychological, neuroendocrine, and immune mediators of stressful life events on exacerbation may lead to new behavioural and pharmacological strategies targeting potential links between stress and exacerbation.


  • Contributors DCM initially conceived the paper and is guarantor. All authors participated in data acquisition, analysis, and writing.

  • Funding US National Institutes of Health grants R01 MH59708-01 and R01 HD043323-01 and National Multiple Sclerosis Society grants FG 1481-A1 and FG 1376A1.

  • Conflict of interest None declared.

  • Ethical approval Not required.

  • Accepted 22 January 2004
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