title: Dysregulated stress signal sensitivity and inflammatory disinhibition as a pathophysiological mechanism of stress-related chronic fatigue.
abstract: Chronic stress and its subsequent effects on biological stress systems have long been recognized as predisposing and perpetuating factors in chronic fatigue, although the exact mechanisms are far from being completely understood. In this review, we propose that sensitivity of immune cells to glucocorticoids (GCs) and catecholamines (CATs) may be the missing link in elucidating how stress turns into chronic fatigue. We searched for in vitro studies investigating the impact of GCs or CATs on mitogen-stimulated immune cells in chronically stressed or fatigued populations, with 34 original studies fulfilling our inclusion criteria. Besides mixed cross-sectional findings for stress- and fatigue-related changes of GC sensitivity under basal conditions or acute stress, longitudinal studies indicate a decrease with ongoing stress. Research on CATs is still scarce, but initial findings point towards a reduction of CAT sensitivity under chronic stress. In the long run, resistance of immune cells to stress signals under conditions of chronic stress might translate into self-maintaining inflammation and inflammatory disinhibition under acute stress, which in turn lead to fatigue.
authors.affiliation: Clinical Biopsychology, University of Marburg, Gutenbergstrasse 18, Marburg, 35037, Germany. Electronic address: strahler@uni-marburg.de.
authors.forename: Jana
authors.initials: J
authors.lastname: Strahler
authors.affiliation: Clinical Biopsychology, University of Marburg, Gutenbergstrasse 18, Marburg, 35037, Germany. Electronic address: Skoluda@uni-marburg.de.
authors.forename: Nadine
authors.initials: N
authors.lastname: Skoluda
authors.affiliation: Health Psychology, Friedrich-Alexander-University Erlangen-Nuremberg, Nägelsbachstrasse 49a, Erlangen, 91052, Germany. Electronic address: nicolas.rohleder@fau.de.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Rohleder
authors.affiliation: Clinical Biopsychology, University of Marburg, Gutenbergstrasse 18, Marburg, 35037, Germany. Electronic address: nater@uni-marburg.de.
authors.forename: Urs M
authors.initials: UM
authors.lastname: Nater
mesh_terms: D003430:Cross-Sectional Studies; D005221:Fatigue; D005938:Glucocorticoids; D007249:Inflammation; D010913:Pituitary-Adrenal System; D013312:Stress, Physiological
chemical_list: D005938:Glucocorticoids
keywords: Autonomic nervous system; Chronic fatigue; Chronic stress; HPA axis; Inflammation; Stress signal sensitivity