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Explanation of the mechanism of exhaustion and feeling tired from a psychological


Fatigue is a common symptom in somatic and mental illness. Musculoskeletal pain and psychological distress have in turn frequently been shown to be associated with fatigue across clinical conditions and in the general population. The study aims to disentangle direct effects from those due to mere confounding from shared etiologies.


The study used genetically informative longitudinal twin data, through a co-twin control design with an additional within-person dimension.


Data on fatigue, pain and distress from 2196 mono – and dizygotic twins from the Norwegian Twin Registry examined at two time points five years apart was analyzed using multilevel generalized linear regression modeling. Fatigue was regressed on pain and distress, with further controls added for confounding from genetic and stable non-shared environmental sources.


Pain and distress had a significant impact on fatigue at genetic, stable non-shared environmental and time-varying levels, even when controlling for somatic comorbidity.


The findings indicate that a significant proportion of the association between fatigue, pain and distress is due to genetic and environmental confounding. Pain and distress exert significant, albeit smaller effects on fatigue even when controlling for genetic and stable environmental contributions, indicating direct effects. Potential etiological pathways and underlying mechanisms are discussed.

KEYWORDS: Fatigue, pain, psychological distress, behavioral genetics


The experience of fatigue involves strong sensations of mental and physical tiredness, weakness, exhaustion, and difficulty with concentration. One definition conceptualizes fatigue as an awareness of a decreased capacity for physical or mental activity due to an imbalance in the availability, utilization or restoration of resources needed to perform an activity (Aaronson et al., ). Life stressors and homeostatic factors (i.e. overexertion) may contribute to acute fatigue in otherwise healthy individuals (Finsterer & Mahjoub, ). For some, however, the symptom may linger and take on a persistent, chronic form (Duncan, Wu, & Mead, ; Mollayeva et al., ), which is the case in, e.g. Chronic Fatigue Syndrome (CFS) (also denoted Myalgic Encephalomyelitis (ME)) (Cortes Rivera, Mastronardi, Silva-Aldana, Arcos-Burgos, & Lidbury, ). Fatigue is frequently reported in general primary care and community studies, and the exact threshold between common fatigue (e.g. ‘feeling tired and weak’) and diagnosable CFS can be arbitrary. Fatigue is therefore presumably best conceptualized as a continuously distributed symptom in the general population (Bültmann, Kant, Kasl, Beurskens, & van den Brandt, ; Loge, Ekeberg, & Kaasa, ).