0300 STRESS SYSTEM DYSREGULATION IN INSOMNIA DISORDER

Abstract

Insomnia disorder (ID) is highly co-morbid with chronic pain conditions. Dysregulation of the hypothalamus-pituitary adrenal (HPA) stress system suggests a contribution to both ID and chronic pain. We investigated HPA system integrity in individuals with ID, indicated by measures of resting cortisol levels and IL-6 expression in monocytes, glucocorticoid (GC) sensitivity (i.e., sensitivity of cells to the counter-inflammatory signal cortisol), and reactivity of cortisol to a repeated challenge. We hypothesized deterioration of HPA system integrity may represent a mechanistic pathway by which ID increases chronic pain vulnerability. This is an ongoing study with N=19 participants (ages 18–49). Seven participants (1 male) diagnosed of insomnia disorder (ID) based on DSM-V criteria and 12 healthy controls (HC;3 male) completed an overnight polysomnographic (PSG) sleep recording in the Clinical Research Center. The following morning, resting blood samples were collected for measurements of basal serum cortisol levels, IL-6 positive monocytes, and GC sensitivity of monocytes as assessed by flow cytometry. To determine serum cortisol reactivity, participants completed a cold pressor test (CPT) challenge three times in succession (1300,1430,1600) by placing their hand in a temperature-controlled cold water bath for at least one minute. Blood was drawn 20 and 50 minutes after each CPT to measure post-challenge cortisol levels. ID participants had significantly shorter PSG sleep duration (ID:341 ± 110 min; HC:422 ± 31 min). Basal cortisol levels, IL-6 positive monocytes and GC sensitivity did not differ between groups, but cortisol levels in the ID group were significantly higher 20 min (ID:14.24 ± 3.34μg/dL; HC:10.86 ± 2.38μg/dL) and 50 min (ID:11.46 ± 2.40μg/dL; HC:8.99 ± 2.04μg/dL) after the first CPT challenge, and 20 min after the second CPT challenge (ID:11.24 ± 3.59; HC:7.92 ± 1.59μg/dL). While basal levels of cortisol, IL-6 expression by monocytes, and GC sensitivity did not significantly differ between ID and HC cortisol reactivity in the first and second CPT challenge was increased. These preliminary results suggest a stronger stress system responsiveness to novel challenges, which may mechanistically contribute to the relationship between ID and vulnerability to chronic pain. Investigator-initiated grant from Merck Inc., NIH/UL1 RR02758 and M01-RR-01032 from National Center for Research Resources to Harvard Clinical and Translational Science Center.