Severe fatigue in adolescents : psychological, neuro-endocrine, and immunological characteristics

Abstract

Fatigue is a common complaint among adolescents. In a pilot study, we observed 8% of healthy adolescents to report fatigue severity which was comparable to fatigue severity reported by chronic fatigue syndrome (CFS) patients. This observation led to an extensive investigation on psychological, neuro-endocrine, and immunological characteristics of severe fatigued in adolescents. In an epidemiological study, we investigated the prevalence of severe fatigue, its comorbidities and the role of life style. In a sample of 3454 high school students, 20.5% of girls and 6.5% of boys reported severe fatigue on a standardized questionnaire. Despite this female preponderance, in both genders fatigue was strongly related to depression, anxiety and CFS-related symptoms, such as pain, unrefreshing sleep, and cognitive problems. In a longitudinal study among girls, we revealed that the onset and persistence of fatigue was predicted by emotional problems. In addition, life style played a minor role in fatigue. Reduced physical activity and night rest were related to fatigue as well. To investigate whether fatigue was related to physiological disturbances, we selected a subgroup of severely fatigued and non-fatigued female participants and tested them on three occasions during one year. We compared these two groups on functions of the hypothalamus-pituitary-adrenal (HPA)-axis and the immune system since previous research showed dysfunctions in these systems in CFS patients. Cortisol Awakening Response (CAR), which is a commonly used read out of adrenal functioning, did not differ between the fatigued and non-fatigued group, neither did results on the low-dose dexamethasone (DEX) suppression test, which tests the negative feedback function of the HPA-axis. Basal cortisol measured in plasma, on the other hand, was higher in fatigued participants than in non-fatigued girls. Groups did not differ in mitogen-induced cytokine production and T-cell proliferation. Yet, a subgroup of fatigued girls with high levels of emotional comorbidity had a skewing in cytokine production towards an anti-inflammatory milieu. Also, a small sample of adolescent CFS patients produced relatively more anti-inflammatory cytokines. Receptor sensitivity of T-cells and monocytes to DEX did not differ between fatigued and non-fatigued participants, suggesting no dysfunctions of the immune system and the interactions between the immune system and the HPA-axis. However, also in these analyses we discovered deviations in a subgroup of fatigued participants. T-cell receptor sensitivity to DEX was reduced in participants with persistent fatigue. All immune functions measured in our studies showed seasonal variation, with systematically different values in spring compared to autumn. Nevertheless, relatively to the other participants of the group, values of each individual were fairly stable. We conclude that, the involvement of emotional problems in the onset and persistence of fatigue suggests that both preventive and therapeutic strategies with respect to fatigue treatment in adolescents should concentrate on emotional well being. Moreover, adolescents at risk should be stimulated to spend more time on physical activities and to sleep longer. Although fatigue is frequently reported, neuro-endocrine and immunological functions are not always affected. It would be interesting to investigate whether the subgroups of participants with physiological deviations have a higher risk to develop fatigue-related illnesses in the future