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

Background: Fatigue symptoms are associated with a variety of syndromes and diseases, but in many cases no specific underlying disease activity or psychiatric condition can be found. Both common fatigue conditions and the more... [ view full abstract ]

Background: Fatigue symptoms are associated with a variety of syndromes and diseases, but in many cases no specific underlying disease activity or psychiatric condition can be found. Both common fatigue conditions and the more serious chronic fatigue syndrome (CFS) have been shown to be linked to pain symptoms, particularly musculoskeletal (MS) pain, and to negative affect symptoms such as anxiety and depression. However, the nature of this relationship is poorly understood. In the present study the genetic and environmental association between anxiety-depression, 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). Using Cholesky modeling, genetic and environmental influences on neuroticism, anxiety-depression, MS and fatigue symptoms, and the associations among these phenotypes, were determined. Results: The best-fitting biometric models included additive genetic and individual-specific environmental effects. All four phenotypes were moderately to strongly influenced by genetic factors [heritability (h²) = 0.40-0.53]. 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. The independent genetic influence of MS pain on fatigue was substantial, and the genetic correlation between the two phenotypes was particularly strong (i.e., 0.88). 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.