Fatigue is a symptom characterised by a subjective experience of decreased capacity for activity and an increased need for rest, which is disproportionate to the effort expended. While fatigue is commonly observed in association with a wide range of chronic illnesses and interest in research on this symptom is steadily increasing, clear recommendations for its assessment, treatment and management remain lacking. Although research has identified several biopsychosocial mechanisms associated with fatigue, much remains to be identified in terms of the crucial mechanisms for fatigue treatment. Furthermore, potential confounders such as genetic and dispositional vulnerabilities may complicate our perception of the relationships between fatigue and other symptoms as being causal, while their co-occurrence may in fact only stem from shared vulnerabilities.
Patients with traumatic brain injury (TBI) often struggle with fatigue following injury. Fatigue is commonly reported in the early phases following injury and remains a troublesome symptom for many patients in the later phases of adaptation to life with the sequela of TBI.
While earlier research has established an abundance of associations between fatigue and various biological, psychological and social factors, much remains to be explored regarding the exact nature of these relationships. In relation to TBI, severe injuries are often associated with more severe cognitive, emotional and functional deficits. Despite this, associations are rarely found between injury severity and fatigue, or these are found to be marginal when significant associations have been documented. Similarly, no specific localisation of brain injury has been linked to an increased risk of fatigue, despite progress being made into neural underpinnings of the symptom. While cognitive dysfunction has been associated with fatigue in some studies, it has rarely accounted for much of the variation in fatigue. Self-reported biopsychosocial factors such as pain, depressive symptoms and trait neuroticism generally demonstrate more robust associations with fatigue than objective measures such as the severity of somatic illness and performance-based cognitive tests in TBI, other health conditions and the general population.
Much of the research into fatigue has revolved around examining cross-sectional hypotheses, with the primary aim of characterising those patients who develop persistent fatigue following injury, and those who do not. For the research field to move beyond mere correlation and towards verification or falsification of causal assumptions, studies need to incorporate measures for dealing with confounding from shared vulnerabilities between fatigue and its correlates.
The overall aims of this thesis were to (1) explore the biopsychosocial correlates of fatigue using an improved and parsimonious characterisation of risk and protective factors and (2) identify the factors associated with fatigue over time. In the pursuit of a clearer understanding of how the mechanisms in this vast network of symptoms interact, this doctoral thesis has approached the problem from various angles in three scientific papers.
In Paper I, the primary aim was to examine (1) the behavioural genetic underpinnings of fatigue in a sample of mono- and dizygotic twins from the general population and (2) the degree of shared genetic and stable or time-varying environmental influences between fatigue, pain and psychological distress.
In Paper II, the primary aim was to explore potential parsimonious structures underlying the commonly implicated biopsychosocial mechanisms involved in the initiation, maintenance, and exacerbation of fatigue 6 months after TBI.
In Paper III, the aim was to better understand which factors contribute to the persistence and amelioration of fatigue from 6 to 12 months after TBI via an exploration of the between- and within-subject biopsychosocial correlates of fatigue.
The findings indicate that several biopsychosocial factors can be used to identify which individuals are at risk of developing fatigue following injury, while a smaller group of factors also covary with fatigue within subjects. Pain, somatic symptom burden, psychological distress and behavioural inhibition were implicated as the crucial factors to address within rehabilitation aimed at the amelioration of fatigue following injury. Combined, the studies described in these papers shed light on novel ways of understanding fatigue. As such, they may guide future research and clinical efforts aimed at managing fatigue through a parsimonious taxonomy of protective and vulnerability factors involved in the initiation, maintenance and exacerbation of fatigue following TBI.