Psychological Medicine

Original Articles

Chronic fatigue in a population sample: definitions and heterogeneity

a1 Departments of Genetics, Psychiatry and Epidemiology, University of North Carolina at Chapel Hill, NC, USA
a2 Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden
a3 Department of Psycholog y, University of Southern California, Los Angeles, CA, USA
a4 Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden

Article author query
sullivan pf   [PubMed][Google Scholar] 
pedersen nl   [PubMed][Google Scholar] 
jacks a   [PubMed][Google Scholar] 
evengard b   [PubMed][Google Scholar] 


Background. Numerous nosological decisions are made when moving from the common human symptom of unusual fatigue to the rare chronic fatigue syndrome (CFS). These decisions have infrequently been subjected to rigorous evaluation.

Method. We obtained telephone interview data on fatiguing symptoms from 31406 individuals twins in the Swedish Twin Registry aged 42–64 years; 5330 subjects who endorsed fatigue and possessed no exclusionary condition formed the analytic group. We evaluated the definition and classification of CFS-like illness using graphical methods, regression models, and latent class analysis.

Results. Our results raise fundamental questions about the 1994 Centers for Disease Control criteria as (1) there was no empirical support for the requirement of four of eight cardinal CFS symptoms; (2) these eight symptoms were not equivalent in their capacity to predict fatigue; and (3) no combination of symptoms was markedly more heritable. Critically, latent class analysis identified a syndrome strongly resembling CFS-like illness.

Conclusions. Our data are consistent with the ‘existence’ of CFS-like illness although the dominant nosological approach captures population-level variation poorly. We suggest that studying a more parsimonious case definition – impairing chronic fatigue not due to a known cause – would represent a way forward.

c1 Department of Genetics, CB#7264, 4109D Neurosciences Research Building, University of North Carolina, Chapel Hill, NC 27599-7264, USA. (Email: