Hypothalamic–pituitary–adrenal (HPA) axis response to exogenous corticotropin‐releasing hormone (CRH) is attenuated in men with chronic insomnia

Abstract

Although insomnia is by far the most common sleep disorder, our understanding of its neurobiology is limited. Insomnia, particularly when associated with objective sleep disturbance, has been associated with activation of the hypothalamic-pituitaryadrenal axis. The objective of this experimental study was to compare the response of the hypothalamic-pituitary-adrenal axis to ovine corticotropin-releasing hormone, a stress test, in men with insomnia versus controls. Circulating adrenocorticotropic hormone and cortisol levels were assayed before (−30 min, −15 min), at (0 min) and after (+5 min, +15 min, +30 min, +60 min, +90 min, +120 min) exogenous ovine corticotropin-releasing hormone administration in 23 men (11 insomnia, 12 controls), who underwent four consecutive nights of in-lab polysomnography. Men with insomnia compared with controls demonstrated markedly and significantly shorter total sleep time (368.4 ± 8.99 min versus 411.61 ± 8.61 min; p < 0.01) and lower sleep efficiency (76.77 ± 1.80% versus 86.04 ± 1.72%; p < 0.01) on polysomnography, and showed decreased adrenocorticotropic hormone and cortisol levels after ovine corticotropin-releasing hormone administration. Adrenocorticotropic hormone levels at 15 min and 30 min were significantly lower in men with insomnia than in controls (p < 0.05). Similarly, the peak levels of cortisol at +60 min, and the total and net area under the curve levels of this hormone were significantly lower in men with insomnia than controls (all p < 0.01). Adrenocorticotropic hormone and cortisol response to ovine corticotropin-releasing hormone administration was attenuated in men with insomnia associated with objective sleep disturbance, suggesting that objectively defined insomnia subtypes have a disrupted hypothalamic-pituitary-adrenal axis function and highlight the need to develop treatments targeting the underlying hypothalamic-pituitary-adrenal axis dysregulation.

Association between Insomnia Symptoms and Risk of Heart Failure: A Meta-analysis of Prospective Cohort Studies

“…Firstly, in terms of the neuroendocrine system, insomnia is characterized by hyperarousal and chronic activation of stress responses, including increased activity in the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system 24 . These results in elevated cortisol levels, upregulation of the renin-angiotensin-aldosterone system, and increased heart rate, decreased heart rate variability, and elevated blood pressure, all of which are known risk factors for HF 25,26 . Secondly, in terms of inflammation, insomnia is associated with the increased secretion of pro-inflammatory cytokines and catecholamines, further contributing to the HF risk 27 .…”

“…heart rate variability, and elevated blood pressure, all of which are known risk factors for HF 25,26 . Secondly, in terms of inflammation, insomnia is associated with the increased secretion of pro-inflammatory cytokines and catecholamines, further contributing to the HF risk 27 .…”

Sleep duration and the risk of new-onset arthritis in middle-aged and older adult population: results from prospective cohort study in China

“…Sleep is crucial for maintaining the neuroendocrine balance of the immune system. Insufficient sleep disrupts the hypothalamic–pituitary–adrenal (HPA) axis ( 33 ) and sympathetic nervous system (SNS) ( 34 ), increasing inflammatory responses and interfering with hormone levels. Correspondingly, this in turn may regulate neural adaptability and innate immune response ( 35 ).…”

COVID-19-related social isolation and symptoms of depression and anxiety in young men in Poland: Does insomnia mediate the relationship?

“…Human and animal investigations of neuroendocrine stress mechanisms suggest that social isolation increases activation of the HPA axis [ 39 ]. Similarly, dysfunction of the HPA axis is implicated in the pathogenesis of insomnia [ 40 ], which has been considered a physiological “hyperarousal” disorder, reflected by HPA axis activation [ 41 ]. Moreover, research findings point to the possibility of HPA axis overactivity in insomnia and both depression [ 42 ] and anxiety [ 43 ].…”