Can sustained arousal explain the Chronic Fatigue Syndrome?

Vegard B Wyller, Hege R Eriksen, Kirsti Malterud, Vegard B Wyller, Hege R Eriksen, Kirsti Malterud

Abstract

We present an integrative model of disease mechanisms in the Chronic Fatigue Syndrome (CFS), unifying empirical findings from different research traditions. Based upon the Cognitive activation theory of stress (CATS), we argue that new data on cardiovascular and thermoregulatory regulation indicate a state of permanent arousal responses - sustained arousal - in this condition. We suggest that sustained arousal can originate from different precipitating factors (infections, psychosocial challenges) interacting with predisposing factors (genetic traits, personality) and learned expectancies (classical and operant conditioning). Furthermore, sustained arousal may explain documented alterations by establishing vicious circles within immunology (Th2 (humoral) vs Th1 (cellular) predominance), endocrinology (attenuated HPA axis), skeletal muscle function (attenuated cortical activation, increased oxidative stress) and cognition (impaired memory and information processing). Finally, we propose a causal link between sustained arousal and the experience of fatigue. The model of sustained arousal embraces all main findings concerning CFS disease mechanisms within one theoretical framework.

Figures

Figure 1
Figure 1
Normal arousal response, according to the Cognitive activation theory of stress (CATS). A threat to homeostasis elicits an arousal response, characterized by nervous and endocrine adjustments aiming at regaining homeostatic stability (1). This compensatory mechanism is mutually connected to cognitive processes; in addition, it is influenced by personality, genetic traits and sensitization (2). If successful, i.e. if homeostasis is restored, the arousal response is turned off (3).
Figure 2
Figure 2
Proposed model of the origin of sustained arousal in Chronic fatigue syndrome. Certain threats to homeostasis, such as long-lasting infections and psychosocial challenges, may elicit a prolonged arousal response, which does not, however, solve the initial problem (1). The mutual relation to cognitive processes results in negative stimulus and response outcome expectancies, creating a vicious circle (2). Certain genetic traits and aspects of personality may reinforce the arousal response further. This situation causes homeostatic instability in itself, establishing another vicious circle (3). In addition, the arousal response may eventually become associated with neutral events, such as moderate physical activity, through the process of classical conditioning (4). We propose that these mechanisms altogether elicit a state of sustained arousal (5).
Figure 3
Figure 3
Proposed model on the consequences of sustained arousal in CFS. Sustained arousal may cause alterations of immunity, skeletal muscle, cognitions, endocrine function and hemodynamics. Some of these alterations may in turn establish vicious circles due to altered cytokine pattern, oxidative tissue damage and insufficient coping. Finally, sustained arousal might be directly responsible for the experience of fatigue in these patients.

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