Glucocorticoid and inflammatory reactivity to a repeated physiological stressor in insomnia disorder☆

Abstract

Despite known associations of insomnia disorder with alterations in cytokine and glucocorticoid (GC) production, neither the sensitivity of immune cells to a GC signal nor the reactivity of the hypothalamus-pituitary-adrenal (HPA) axis and inflammatory system to stress, or adaptation of these systems to repeated stress have been assessed in patients with insomnia. To investigate potential dysregulation in stress reactivity and adaptation to repeated exposure, a physiological stressor (the cold pressor test; CPT) was repeatedly administered to N\u202f=\u202f20 participants with insomnia disorder (based on DSM-V, 18 females, age 30\u202f±\u202f2.5 years) and N\u202f=\u202f20 sex-matched healthy controls following an at-home actigraphy and in-laboratory PSG. HPA and inflammatory markers (serum cortisol, plasma interleukin [IL]-6) were measured at baseline/resting levels and following each of the three CPTs. In addition, sensitivity of monocytes to the synthetic GC dexamethasone was assessed in-vitro at baseline levels in order to examine the cortisol-IL-6 interplay at the cell level. Compared to healthy controls, individuals with insomnia disorder exhibited shorter sleep duration as assessed by actigraphy and PSG (p\u202f≤\u202f0.05). HPA, but not inflammatory reactivity to the repeated CPT challenge was greater in insomnia disorder (p\u202f≤\u202f0.05 for group effect), due to greater cortisol responses to the initial CPT (p\u202f≤\u202f0.05). There were no between-group differences in the ability of the HPA to adapt to stress repetition nor in basal/resting levels of cortisol, IL-6, and GC sensitivity. These findings suggest that insomnia disorder potentiates HPA axis reactivity to initial/novel stressors, which may constitute a pathway underlying adverse health consequences in the long term.