Association Between Sleep Reactivity, Pre-Sleep Arousal State, and Neuroendocrine Hormones in Patients with Chronic Insomnia Disorder

Ke Yu,1 Lan Xia,1 Hui-Hui Chen,1 Tian-Tian Zou,1 Yu Zhang,1 Ping Zhang,1 Ye Yang,1 Ru-Meng Wei,1 Zeng-Feng Su,2 Gui-Hai Chen1 1Department of Neurology (Sleep Disorder), The Affiliated Chaohu Hospital of Anhui Medical University, Hefei (Chaohu), Anhui Province, 238000, People’s Republic of China; 2Department of General Practice, The Affiliated Chaohu Hospital of Anhui Medical University, Hefei (Chaohu), Anhui Province, 238000, People’s Republic of ChinaCorrespondence: Gui-Hai Chen, Department of Neurology (Sleep Disorders), The Affiliated Chaohu Hospital of Anhui Medical University, Hefei (Chaohu), 238000, People’s Republic of China, Email [email protected] Zeng-Feng Su, Department of General Practice, The Affiliated Chaohu Hospital of Anhui Medical University, Hefei (Chaohu), 238000, Anhui Province, People’s Republic of China, Email [email protected]: The purpose of this study was to look into the relationship between pre-sleep arousal state, sleep reactivity, and serum levels of neuroendocrine hormones (cortisol, copeptin, and corticotropin-releasing hormone) in patients with chronic insomnia disorders (CID), and whether the effects of sleep reactivity and pre-sleep arousal on insomnia are related to the levels of these neuroendocrine hormones.Patients and Methods: This study included 61 CID patients and 27 healthy controls (HC) whose base data were matched to those of the CID patients. The Pittsburgh Sleep Quality Index(PSQI), Pre-Sleep Arousal Scale (PSAS), and the Ford Insomnia Response to Stress Test (FIRST) were used to evaluate the participants’ sleep, stress, and neuropsychological function. We measured the participants’ serum concentration levels of cortisol, copeptin, and corticotropin-releasing hormone (CRH), using quantitative sandwich enzyme-linked immunosorbent assays.Results: The CID group had significantly greater serum levels of copeptin, CRH, and cortisol, as well as higher FIRST and PSAS scores than the HC group. The partial correlation analysis revealed a substantial and positive association among cortisol, CRH, copeptin PSQI, PSAS, and FIRST after adjusting for sex, age, depression, and cognition. Principal component analysis showed that PSQI, FIRST, and PSAS, as well as cortisol, CRH, and copeptin, were all loaded on factor 1.Conclusion: Patients with CID showed increased sleep reactivity and pre-sleep arousal, which correlated with serum levels of cortisol, copeptin, and CRH. Changes in neuroendocrine hormone levels may influence how pre-sleep arousal and sleep reactivity affect the development of insomnia.Keywords: chronic insomnia disorder, pre-sleep arousal, sleep reactivity, hormones, neuroendocrine