Influence of corticotropin releasing hormone receptor type 1 genotype on changes of hypothalamo-pituitary-adrenocortical hormones and sleep after Trier social stress test

Introduction:

The Trier social stress test (TSST) is well established to induce psychological stress in human experiments. So far the effect of TSST, performed in the late evening, on sleep and on stress hormone secretion before sleep onset was not examined. The corticotropin releasing hormone receptor type 1 (CRH R1) gene encodes the CRHR1 receptor. This protein is essential in the activation of the stress response of the hypothalamo-pituitary-adrenocortical (HPA) system. Variants of the single nucleotide polymorphism (SNP) rs110402 of the CRHR1 gene were shown to influence the risk to develop depression after childhood maltreatment. This risk is elevated in homozyguous C carriers of this SNP, whereas TT carriers appear to be more resilient to this risk. We examined the effect of TSST on sleep and HPA hormones and whether this effect is influenced by the CRHR 1 genotype.

Methods:

52 male healthy volunteers, 20 to 30 years old, without any history of childhood trauma or any other risk of psychiatric disorder in their own and family history, were selected for their CRHR1 genotype. According to randomized schedule 31 CC and 21 TT carriers underwent two sessions, separated by one week. Each session consisted of one night of adaptation and one polysomnography (PSG, 23.00 to 07.00) in our sleep laboratory. Before PSG subjects were either exposed to a TSST from 22.30 to 22.40 or underwent a control setting without stress. Mental stress before and after TSST was assessed by visual analogue scale. Saliva for later analysis of cortisol and cortisone was collected four times between 20.00 and 22.55.

Results:

The TT carriers showed significantly higher cortisol reactivity compared to the CC. Cortisone increased without effect of genotype. The perceived stress was inversely to the cortisol reactivity for the CC carriers significantly higher than for the TT carriers. Analysis of polysomnography showed reduced time spent in rapid eye movement (REM) sleep, elevated percentage of wakefulness during sleep period time and prolonged sleep onset latency after TSST compared to baseline irrespective of genotype.

Conclusion:

Our findings suggest that psychosocial stress by TSST stimulates HPA hormone secretion and impairs sleep. The changes of subjectively perceived stress and of cortisol levels were influenced by CRHR1 genotype. Interestingly healthy CC carriers without history of childhood maltreatment show elevated mental stress and reduced cortisol response after TSST. Changes of cortisone and of sleep after TSST were independent of CRHR1 genotype.