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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77 Scopus citations


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

Bibliographical note

Funding Information:
Cytokine testing was supported In part through funding from the National lnstltute of Allergy and Infectious Disease. Antibody testing for Babesia microfi was suooorted In Dart bv Public Health Service grants Al-32403, Al-30548, and AR414<7 fro& the National institutesof Health and grant U5O/CCUS10343 from the Centers for Disease Control and Prevention. Reouests for reorints should be addressed to Kristine L. MacDonald MD, MPH, Minnesbta Department of Health, 717 Southeast Delaware Street, Minneapolis, Minnesota 55440-9441. Manuscript submitted August 28, 1995 and accepted January 9, 1996.

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