Alterations in Hypothalamus-Pituitary-Adrenal/Thyroid Axes and Gonadotropin-Releasing Hormone in the Patients with Primary Insomnia: A Clinical Research

Abstract

The hypothalamus-pituitary-target gland axis is thought to be linked with insomnia, yet there has been a lack of further systematic studies to prove this. This study included 30 patients with primary insomnia (PI), 30 patients with depression-comorbid insomnia (DCI), and 30 healthy controls for exploring the alterations in the hypothalamus-pituitary-adrenal/thyroid axes’ hormones and gonadotropin-releasing hormone (GnRH). The Pittsburgh Sleep Quality Index was used to evaluate sleep quality in all subjects. The serum concentrations of corticotrophin-releasing hormone (CRH), thyrotrophin-releasing hormone (TRH), GnRH, adrenocorticotropic hormone (ACTH), thyroid stimulating hormone (TSH), cortisol, total triiodothyronine (TT3), and total thyroxine (TT4) in the morning (between 0730 h and 0800 h) were detected. Compared to the controls, all hormonal levels were elevated in the insomniacs, except ACTH and TSH in the PI group. Compared to the DCI patients, the PI patients had higher levels of CRH, cortisol, TT3, and TT4 but lower levels of TRH, GnRH, and ACTH. Spearman’s correlation analysis indicated that CRH, TRH, GnRH, TSH, cortisol, TT4, and TT3 were positively correlated with the severity of insomnia. The linear regression analysis showed that only CRH, GnRH, cortisol, and TT3 were affected by the PSQI scores among all subjects, and only CRH was included in the regression model by the “stepwise” method in the insomnia patients. Our results indicated that PI patients may have over-activity of the hypothalamus-pituitary-adrenal/thyroid axes and an elevated level of GnRH in the morning.

Patients with chronic insomnia have selective impairments in memory that are modulated by cortisol

“…However, it is possible that alterations in neuroendocrine hormones, including hormones of the HPA axis, the HPT axes, and GnRH, have detrimental effects on memory formation, synaptic plasticity, and neurogenesis (Fuite, Vernon, & Broderick, ; Kamath, Yarbrough, Prange, & Winokur, ; Morale et al, ; Rohleder, Schommer, Hellhammer, Engel, & Kirschbaum, ). Both our previous study (Xia et al, ) and the present study showed that patients with insomnia had elevated morning serum levels of CRH, cortisol, TRH, total triiodothyronine, total thyroxine, and GnRH (Figure and Table ). Therefore, it is possible these alterations in hormone levels exert a negative effect on multiple aspects of the memory system in patients with insomnia.…”

“…In addition, hormones of the hypothalamic-pituitarythyroid (HPT) axis and hypothalamic-pituitary-gonadal axis influence memory function (Galea et al, 2013;Gan & Pearce, 2012;Grigorova & Sherwin, 2012). Our previous study found neuroendocrine alterations in patients with chronic primary insomnia (Xia, Chen, Li, Jiang, & Shen, 2013); however, the role of neuroendocrine alterations in the memory impairments observed in patients with chronic insomnia disorder (CID) is unclear.…”

The exploratory power of sleep effort, dysfunctional beliefs and arousal for insomnia severity and polysomnography‐determined sleep

“…Our result that PSG‐determined TST was predicted by somatic presleep arousal supports the hyperarousal model of insomnia (Riemann et al ., ). Research suggests that a persistent increase of physiological arousal in patients with PI is associated with reduced activity of the parasympathetic nervous system (Farina et al ., ; Spiegelhalder et al ., ; Yang and Lo, ) and increased activity of the hypothalamic–pituitary–adrenal axis (HPA axis) (Xia et al ., ; Zhang et al ., ) as shown, for example, by increased cortisol levels. Some evidence also suggests that increased cortisol levels were correlated with PSG‐determined sleep disturbance (Vgontzas et al ., , ).…”

Hyperarousal and Beyond: New Insights to the Pathophysiology of Insomnia Disorder through Functional Neuroimaging Studies

“…Physiological studies of patients with primary insomnia (PI) and good sleeper controls (GS) have identified peripheral nervous system (PNS) markers of hyperarousal that seem to support this intuitive explanation, linking insomnia to heightened body temperature [2], greater 24-h metabolic rate [3], and more rapid heart rate and elevated low-frequency power in heart rate, a marker of sympatho-vagal balance, during sleep [4]. Heightened cortisol levels, particularly in the pre- and early-sleep periods, have also been linked to insomnia, a finding interpreted by some as evidence of central nervous system (CNS) hyperarousal in insomnia [5,6,7,8]. …”