Table of Contents:
The aim of this thesis was to find out which factors predict and increase fatigue in everyday life with the aim of shedding light on mechanisms relevant for the chronification of fatigue. We expected stress to (prospectively) predict fatigue. Also, we expected fatigue to (prospectively) predict stress because it diminishes subjective coping abilities. Further, we expected hypoactivity of the Hypothalamic Pituitary Adrenal (HPA) axis and hyperactivity of the Autonomic Nervous System (ANS) to be associated with fatigue, and the relationship between stress and fatigue to be mediated by these biological mechanisms. Moreover, sleep quality was expected to mediate the stress-fatigue relationship from one day to the next. Being in a close relationship and physical activity are investigated as important factors directly influencing fatigue, or influencing fatigue mediated by HPA axis and ANS activity.
First, in light of the multitude of existing labels and definitions, we decided to review different attempts to define and classify chronic fatigue conditions and their differentiation from depression (Doerr & Nater, 2013). This review helps to grasp the concept of chronic medically unexplained fatigue and shed light on why difficulties with and conflicts regarding this symptom are present in society. In the first empirical study, we then investigated the influence of stress on fatigue and the mediating capability of HPA axis activity, ANS activity, as well as sleep quality in a student sample. As part of these analyses, we were also interested in whether the stress-fatigue relationship is reciprocal in nature (Doerr et al., 2015). In a second study, relationship-specific influences on fatigue were analyzed using a dyadic ambulatory assessment approach (Doerr, Nater, Spoerri, Ehlert, & Ditzen, ready to be submitted). In a third study, we investigated the association of HPA axis, ANS, and physical activity, with fatigue in a sample of female patients with fibromyalgia syndrome (FMS) (Doerr, Fischer, Nater, & Strahler, under review).
The narrative review revealed that current definitions of syndromes that present with medically unexplained fatigue as the major symptom overlap and cannot be clearly differentiated. Nevertheless, each of their labels has a different underlying functionality, and one should be aware of this before applying them. As concluded in this review, research on the symptom of fatigue is warranted, and not necessarily comparisons between healthy subjects and persons suffering from fatigue syndromes (as they lack valid definitions).
Summary of results from empirical studies:
Stress and fatigue. Stress and fatigue co-varied within persons in the student sample and the FMS sample, but not in the sample of couples. Moreover, we found a prospective reciprocal association between stress and fatigue within days as well as between days in the student sample. Fatigue levels were also heightened in the student sample in the exam condition.
HPA axis activity. Neither in the student sample nor in the sample of couples was there a momentary association between cortisol and fatigue. The CAR emerged as a negative predictor of mean daily fatigue in the FMS sample, but was not associated with fatigue levels in the student sample. Furthermore, momentary cortisol levels were positively associated with physical fatigue in the FMS sample. In the student sample, morning cortisol levels were heightened in the exam condition.
ANS activity. ANS activity, as measured by sAA, only explained variance in momentary fatigue in the women of the couple sample (negative association). It was not associated with fatigue levels in any of the other studies. It was, however, altered (steeper slope) during exam preparation in the student sample.
Sleep quality. Sleep quality was found to be a mediator between mean daily stress levels and mean daily fatigue levels in the student sample.
Relationship-specific influences. Fatigue, stress, and HPA axis activity were co-regulated within couples. Furthermore, ANS activity co-varied with that of the partner in women. Positive interaction with the partner was associated with reduced fatigue levels.
Physical activity. Objectively measured mean daily physical activity was positively associated with mean same-day stress level and negatively associated with mean next-day fatigue in the FMS sample. However, it was not associated with HPA axis or ANS activity.
Studies are now needed that investigate the influence of stress and changes in HPA axis and ANS activity using longer time periods of investigation. The clinical implication that emerges most clearly from our studies is that stress management training can be seen as the most important approach for prevention and treatment of chronic fatigue.