A case-control study to assess possible triggers and cofactors in chronic fatigue syndrome

Kristine L. MacDonald, Michael T Osterholm, Kathleen H. LeDell, Karen E. White, Carlos H Schenck, Chun C. Chao, David H. Persing, Russell C. Johnson, James M. Barker, Phillip K. Peterson

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PURPOSE: To assess possible triggers and cofactors for chronic fatigue syndrome (CFS) and to compare levels of selected cytokines between cases and an appropriately matched control group. PATIENTS AND METHODS: We conducted a case-control study of 47 cases of CFS obtained through a regional CFS research program maintained at a tertiary care medical center. One age-, gender-, and neighborhood-matched control was identified for each case through systematic community telephone sampling. Standardized questionnaires were administered to cases and controls. Sera were assayed for transforming growth factor-β (TGF-β), interleukin-1β, interleukin-6, tumor necrosis factor-α, and antibody to Borrelia burgdorferi and Babesia microti. RESULTS: Cases were more likely to have exercised regularly before illness onset than controls (67% versus 40%; matched odds ratio (MOR) = 3.4; 95% CI = 1.2 to 11.8; P = 0.02). Female cases were more likely to be nulliparous prior to onset of CFS than controls (51% versus 31%; MOR = 8.0; 95% CI = 1.03 to 170; P = 0.05). History of other major factors, including silicone-gel breast implants (one female case and one female control), pre-morbid history of depression (15% of cases, 11% of controls) and history of allergies (66% of cases, 51% of controls) were similar for cases and controls. However, cases were more likely to have a diagnosis of depression subsequent to their diagnosis of CFS compared to a similar time frame for controls (MOR = undefined; 95% CI lower bound = 2.5; P < 0.001). Positive antibody titers to B burgdorferi (one case and one control) and B microti (zero cases and two controls) were also similar. CONCLUSIONS: Further investigation into the role of prior routine exercise as a cofactor for CFS is warranted. This study supports the concurrence of CFS and depression, although pre-morbid history of depression was similar for both groups.

Original languageEnglish (US)
Pages (from-to)548-554
Number of pages7
JournalAmerican Journal of Medicine
Issue number5
StatePublished - May 1996

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    MacDonald, K. L., Osterholm, M. T., LeDell, K. H., White, K. E., Schenck, C. H., Chao, C. C., Persing, D. H., Johnson, R. C., Barker, J. M., & Peterson, P. K. (1996). A case-control study to assess possible triggers and cofactors in chronic fatigue syndrome. American Journal of Medicine, 100(5), 548-554. https://doi.org/10.1016/S0002-9343(96)00017-4