Premorbid predictors of chronic fatigue

Context: Chronic fatigue syndrome is a disabling problem characterized by persistent fatigue lasting at least 6 months with a number of ancillary symptoms. Although the etiology of chronic fatiguing illness is unknown, some evidence suggests that stress may confer increased risk for development of the disorder. Moreover, subjects with chronic fatiguing illness may have distinctive personality traits, although this finding could reflect confounding by other mechanisms. Objective: To assess the prospective association of premorbid self-reported stress and personality with chronic fatigue-like illness. Design: Prospective nested case-control study in a population-based sample. Setting: General community. Participants: From the Swedish Twin Registry, 19 192 twins born between January 1, 1935, and December 31, 1958. Main Outcome Measures: Information about current chronic fatiguing illnesses was obtained from computer-assisted telephone interviews conducted between 1998 and 2002. Self-reported stress (based on a single question) and personality scales (emotional instability and extraversion in the Eysenck Personality Inventory) were measured from 1972 to 1973 by a mailed questionnaire. Relative risks were estimated with case-control analyses ( matched for age and sex) and co-twin control analyses ( comparing discordant pairs). Results: Higher emotional instability and self-reported stress in the premorbid period were associated with higher risk for chronic fatigue-like illness in matched case-control analyses (odds ratios, 1.72 and 1.64, respectively). In co-twin control analyses, relative risk of emotional instability decreased to 1.02 whereas that of stress increased considerably to 5.81. There was no association between extraversion and fatigue. Conclusions: Elevated premorbid stress is a significant risk factor for chronic fatigue-like illness, the effect of which may be buffered by genetic influences. Emotional instability assessed 25 years earlier is associated with chronic fatigue through genetic mechanisms contributing to both personality style and expression of the disorder. These findings suggest plausible mechanisms for chronic fatiguing illness.