Altered ultradian cortisol rhythmicity as a potential neurobiologic substrate for chronic insomnia

Abstract

Chronic insomnia is highly prevalent and associated with significant morbidity (i.e., confers risk for multiple psychiatric and medical disorders, such as depression and hypertension). Therefore, it is essential to identify factors that perpetuate this disorder. One candidate factor in the neurobiology of chronic insomnia is hypothalamic-pituitary-adrenal-axis dysregulation, and in particular, alterations in circadian cortisol rhythmicity. Cortisol secretory patterns, however, fluctuate with both a circadian and an ultradian rhythm (i.e., pulses every 60-120 min). Ultradian cortisol pulses are thought to be involved in the maintenance of wakefulness during the day and their relative absence at night may allow for the consolidation of sleep and/or shorter nocturnal awakenings. It is possible that the wakefulness that occurs in chronic insomnia may be associated with the aberrant occurrence of cortisol pulses at night. While cortisol pulses naturally occur with transient awakenings, it may also be the case that cortisol pulsatility becomes a conditioned phenomenon that predisposes one to awaken and/or experience prolonged nocturnal awakenings. The current review summarizes the literature on cortisol rhythmicity in subjects with chronic insomnia, and proffers the suggestion that it may be abnormalities in the ultradian rather than circadian cortisol that is associated with the pathophysiology of insomnia.

The Effect of sequential bilateral low‐frequency rTMS over dorsolateral prefrontal cortex on serum level of BDNF and GABA in patients with primary insomnia

“…First, a large number of basic and clinical studies have indicated that the cerebral cortex of PI patients is in an excessively awakened state, which leads to excessive hyperactivities of the hypothalamic–pituitary–adrenal axis and hypothalamic–pituitary–thyroid axis function in the body, resulting in elevation of serum corticosterone, adrenocorticotrophic hormone, thyrotropin, and free T3 and T4 levels. Therefore, serum concentrations of these hormones indirectly reflect the cortical arousal level to some extent (Riemann et al, ; Vargas et al, ). Based on this, some researchers have shown that low‐frequency rTMS on the right DLPFC reduces the levels of adrenocorticotrophic hormone, thyroid‐stimulating hormone (TSH), and free T3 and T4 levels in the serum of PI patients (Jiang, Zhang, Yue, Yi, & Gao, ), suggesting that low‐frequency TMS may reduce the excitability of the cortex.…”

Acute and Chronic Insomnia: What Has Time and/or Hyperarousal Got to Do with It?

“…Examples of autonomic measures include heart rate [60], heart rate variability [61], electrodermal activity [62], epinephrine or norepinephrine [63], core body temperature measures [64], and/or metabolic rate measures [65]. Endocrine measures typically include bloodand/or saliva-based measures of cortisol [66,67]. It is important to consider, however, that prior research on the hyperarousal theory of insomnia has mostly observed incremental increases in psychobiological indices (e.g., evening levels in cortisol, core body temperature, glucose metabolism, etc.)…”

Sleep and Wellbeing, Now and in the Future

“…Hang-ups (not being able to let go) at bedtime postpone sleep. Stress, worries and anxiety culminate in heightened arousals with consequential increases in the pulsatility of nocturnal cortisol, when only few, regular cortisol pulses should exist [29].…”