Fatigue symptoms in relation to neuroticism, anxiety-depression, and musculoskeletal pain. A longitudinal twin study

Background: The nature of the relationship between fatigue and its risk factors is poorly understood. In the present study the genetic and environmental association between anxiety-depression, musculoskeletal (MS) pain and fatigue was examined, and the role of neuroticism as a shared risk factor that may possibly explain the co-occurrence between these phenotypes was investigated in a combined cross-sectional and longitudinal twin design. Methods: The sample consisted of 746 monozygotic (MZ) and 770 dizygotic (DZ) twins in the age group of 50–65 (mean = 57.11 years, SD = 4.5). Continuous measures of fatigue symptoms and the other phenotypes were employed. Using Cholesky modeling, genetic and environmental influences on the phenotypes, and the associations among them, were determined. Analyses were performed using measures of neuroticism obtained concurrently and 13–19 years earlier. Results: Results from multiple regression analyses showed that neuroticism, anxiety-depression symptoms, and MS pain were all significantly associated with fatigue, controlling for sex, education, and general health indices. The best-fitting biometric models included additive genetic and individual-specific environmental effects. Heritabilities in the 0.40–0.53 range were demonstrated. Furthermore, while there was a considerable overlap in genetic risk factors between the four phenotypes, a substantial proportion of the genetic risk shared between anxiety-depression and fatigue, and between MS pain and fatigue, was independent of neuroticism. Conclusion: Evidence for a common underlying susceptibility to report fatigue symptoms, genetically linked to neuroticism, anxiety-depression, and MS pain, was found. Both unique and pleiotropic effects appear to be involved in the genetic architecture of the phenotypes.