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. 2001 Jan;16(1):24-31.
doi: 10.1111/j.1525-1497.2001.03419.x.

Comorbid Clinical Conditions in Chronic Fatigue: A Co-Twin Control Study

Free PMC article

Comorbid Clinical Conditions in Chronic Fatigue: A Co-Twin Control Study

L A Aaron et al. J Gen Intern Med. .
Free PMC article


Objectives: Chronically fatiguing illness, defined as fatigue for at least 6 months, has been associated with various physical health conditions. Our objective was to determine whether there is a significant relationship between chronically fatiguing illness and 10 clinical conditions that frequently appear to be associated with fatigue, adjusting for the potentially confounding effects of psychiatric illness.

Design: A co-twin control study controlling for genetic and many environmental factors by comparing chronically fatigued twins with their nonfatigued co-twins.

Setting: A nationally distributed volunteer twin registry.

Participants: The study included 127 twin pairs in which one member of the pair experienced fatigue of at least 6 months' duration and the co-twin was healthy and denied chronic fatigue. Fatigued twins were classified into 3 levels using increasingly stringent diagnostic criteria.

Measurements and main results: Twins reported on a history of fibromyalgia, irritable bowel syndrome, multiple chemical sensitivities, temporomandibular disorder, interstitial cystitis, postconcussion syndrome, tension headache, chronic low back pain, chronic pelvic pain (women), and chronic nonbacterial prostatitis (men). The prevalence of these comorbid clinical conditions was significantly higher in the fatigued twins compared to their nonfatigued co-twins. Most notably, compared to their nonfatigued co-twins, the chronically fatigued twins had higher rates of fibromyalgia (> 70% vs < 10%) and irritable bowel syndrome (> 50% vs < 5%). The strongest associations were observed between chronic fatigue and fibromyalgia (odds ratios > 20), irritable bowel syndrome, chronic pelvic pain, multiple chemical sensitivities, and temporomandibular disorder (all with odds ratios > or = 4). Regression analysis suggested that the number of comorbid clinical conditions associated with chronic fatigue could not be attributed solely to psychiatric illness.

Conclusions: Chronically fatiguing illnesses were associated with high rates of many other clinical conditions. Thus, patients with chronic fatigue may present a complex clinical picture that poses diagnostic and management challenges. Nonetheless, clinicians should assess such patients for the presence of comorbid clinical conditions. Future research should provide a better understanding of the temporal relationship of the onset of fatigue and these conditions, and develop strategies for early intervention.


Odds ratios and 95% confidence intervals for chronic fatigue and the number of comorbid clinical conditions. Model 1 is unadjusted. Model 2 is adjusted for age, sex, zygosity, educational level, marital status, and number of children. Model 3 is adjusted for the sociodemographic factors used in model 2 and the number of nonexclusionary psychiatric disorders.

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