Genetic epidemiological studies of the functional somatic syndromes : chronic widespread pain and chronic fatigue

Abstract: Fibromyalgia and chronic fatigue syndrome are two symptom-defined conditions with many physical symptoms in common, such as muscle pain, fatigue, unrefreshing sleep, and impairment in memory or concentration. These two conditions often co-occur and frequently co-exist with other symptom-defined conditions (e.g., irritable bowel syndrome and recurrent headache), have a female predominance, and share psychosocial or psychiatric characteristics. It has been suggested that fibromyalgia, chronic fatigue syndrome, and other symptom-defined conditions can be considered as syndromes that share underlying pathogenesis, and hence named ¡°functional somatic syndromes¡±. To date, little is known about the causes of functional somatic syndromes and their co-occurrence (comorbidity). The present study aimed at investigating the etiology of this comorbidity with a focus on chronic widespread pain (the cardinal symptom of fibromyalgia) and chronic fatigue. Data were obtained from the participants in the Screening Across the Lifespan Twins (SALT) study of the population-based Swedish Twin Registry. All living, contactable, and consenting twins born in Sweden before December 1958 were contacted between March 1998 and December 2002 to participate in a computer-assisted telephone interview. Of 61,355 eligible twins, 44,897 individuals (73.2%) participated in the interview which screened, amongst others, for chronic widespread pain, chronic fatigue, irritable bowel syndrome, recurrent headache, major depression, and generalized anxiety disorder. Zygosity was determined using questions regarding childhood similarity. Psychological risk factors (personality and stress) were assessed using questionnaires administered to monozygotic and same-sex dizygotic twins in 1972-73. Univariate and multivariate twin analyses were implemented in order to estimate the relative importance of genetic and environmental influences on chronic widespread pain, to assess sex differences in the estimates, and to determine the etiological model that best explains the comorbidity of the functional somatic syndromes. Matched case-control and co-twin case-control analyses were performed in order to evaluate the associations between chronic widespread pain and its comorbid conditions, to examine premorbid risks of psychological factors for chronic fatigue, and to assess familial (genetic and family environmental) influences on these associations. Modest genetic influences and no family environmental influences were found in chronic widespread pain. The estimates did not differ significantly by sex. Strong associations were found between chronic widespread pain and chronic fatigue, followed in magnitude by irritable bowel syndrome. Associations of chronic widespread pain with psychiatric disorders were no longer significant when discordant monozygotic twins were used, whereas associations with most of the other conditions decreased but remained significant, suggesting familial influences on the associations. Emotional instability and perceived stress were significantly associated with chronic fatigue screened ¡Ý 25 years later in subjects aged < 65. When monozygotic twins were used, the association with emotional instability was no longer significant but that with perceived stress increased in the severer definition of chronic fatigue, suggesting different effects of genetic influences on the associations. Finally, for women a model with two latent traits shared by four functional somatic syndromes and two psychiatric disorders best explains the etiology of their comorbidities. The psychiatric disorders loaded on only one of the two latent traits, suggesting that the two latent traits reflect the affective and non-affective (or physiological) aspects of functional symptoms. Each illness is also influenced by genetic and environmental factors specific to each. In conclusion, the comorbidity of functional somatic syndromes is attributed to latent etiological traits (one of which is affective and the other not) shared by these syndromes, whereas the differences among them are attributable to genetic and environmental factors specific to each illness.