Stress-related sleep disturbance and polysomnographic response to caffeine

Abstract

Background and purpose

To determine the sleep response to caffeine in individuals vulnerable to stress-related sleep disturbance as measured by polysomnography.

Patients and methods

Eleven healthy individuals without insomnia scoring low (4 women, mean age=32.64±15.46 years) and 10 healthy individuals also without insomnia scoring high (6 women, mean age=34.20±13.73 years) on a measure of vulnerability to stress-related sleep disturbance were studied in a laboratory protocol. A moderate-low dose of caffeine (3 mg/kg) was administered 1 h prior to lights-out and compared to a counterbalanced control night with each condition separated by 1 week. Standard polysomnographic measures were assessed (i.e. total sleep time, sleep efficiency, latency to persistent sleep, and sleep stage percentages) for both control and caffeine nights.

Results

There were no between-group differences in sleep on the control night. Importantly, individuals reporting vulnerability to stress-related sleep disturbance had significantly prolonged latency to persistent sleep in response to the caffeine challenge (interaction; P<0.05).

Conclusion

Normal sleepers with an identified vulnerability to stress-induced sleep disturbance exhibited greater objectively verifiable sleep-reactivity in response to a caffeine challenge compared to non-vulnerable individuals. These results suggest that the construct of individual differences in vulnerability to sleep disturbance applies to a pharmacological ‘stressor’ (i.e. caffeine) as well as to previously assessed stressors such as a first-night effect. This finding provides further support for generalized trait vulnerability by demonstrating a sleep disturbance to a wake-promoting pharmacological challenge in specific a priori identified individuals.

Introduction

Insomnia is now recognized as one of the most prevalent [1], [2] and costly [3], [4] sleep disorders. Criteria for insomnia in the diagnostic and statistical manual of mental disorders (DSM-IV) include a patient report of difficulty falling asleep, staying asleep, or having non-restorative sleep for a period of at least 4 weeks, associated with impairment in daytime functioning (e.g. occupational, social, other). In addition, these symptoms cannot be accounted for by another medical or psychiatric condition. Studies have begun to document a high degree of morbidity associated with insomnia including reductions in quality of life that are comparable to other chronic illnesses such as congestive heart failure and depression [5], [6].

Although there are a number of well established options available for insomnia treatment [7], data regarding the etiology of this disorder remain sparse. However, there is an increasing body of literature regarding the psychological and physiological differences between insomniacs and good sleepers. Several studies have demonstrated a greater prevalence of intrusive thoughts, worry, and rumination [8], poor sleep hygiene [9], [10], dysregulation of the hypothalamic pituitary axis [11], elevations in sympathetic activity [12], and metabolic rate [13], increased daytime alertness [14], and elevated high-frequency electroencephalographic (EEG) activity [15], [16], [17] in patients with insomnia compared to good sleepers.

Clearly, these data represent a growing body of evidence supporting the association between both cognitive and physiological measures of hyperarousal and insomnia. However, an important question remains. Specifically, what is the temporal relationship between hyperarousal and the development of insomnia as well as the progression of the disorder? Laboratory studies have demonstrated the ability to produce sleep disturbance in healthy good sleepers similar to that of insomniacs through experimental challenges [18], [19]. These findings, along with converging evidence for an elevation in physiological and cognitive arousal measures in insomnia patients, are a first step in determining whether elevated arousal in insomnia represents the underlying pathophysiology of the disorder or a concomitant process resulting from the sleep disturbance itself.

An alternative approach to answering these questions is to study specific aspects of sleep-related processes prior to the onset of the disorder. Although this approach presents many challenges, such as identifying individuals with a ‘high risk’ for developing insomnia, it has produced promising results. We have recently developed [20] and longitudinally validated [21] the Ford Insomnia Response to Stress Test (FIRST), a measure to identify individuals predisposed to sleep disturbance and the subsequent development of chronic insomnia. This nine-item self-report instrument assesses the potential likelihood that an individual will experience sleep disturbance following various stressful events/situations. The FIRST was designed to assess sleep-related ‘reactivity’. While insomniacs do score high on this measure [22], it is not intended to identify insomniacs per se, but rather to determine individuals who may be ‘at risk’ for developing insomnia in the future. Although, as might be expected, scores are elevated in insomniacs [22], preliminary data in non-insomniacs suggests that individuals scoring high on this measure have a greater risk for the development of insomnia over the course of the next year [21]. This instrument has facilitated research on individuals at risk for insomnia to be carried out prior to the development of the disorder.

In a previous study, we demonstrated the existence of a trait vulnerability to hyperarousal and its association with elevated polysomnographically (PSG) measured sleep disturbance in response to the stress of a first night in the laboratory as predicted by the FIRST [20]. However, further studies addressing the beginning stages of the evolution of insomnia are needed. Specifically, the extent to which this trait vulnerability is generalizable to other stressors or challenges beyond those previously assessed has yet to be determined. Furthermore, the characteristic emotional reactivity typically associated with insomnia [23], sometimes alluded to as a ‘predisposing’ factor [24], has rarely been tested using a physiologic challenge. In 2003, Bonnet and Arand [25], assessed the sleep-related response of individuals who demonstrated differentially poor sleep on laboratory adaptation and found that these individuals also had poor sleep in response to caffeine administration and a circadian phase-shift challenge. This demonstrationed the widely held belief that some individuals have a trait vulnerability to situational insomnia. The present study was aimed at comparing the sleep-related reactivity of individuals “a priori” hypothesized to be vulnerable to developing insomnia compared with normal healthy sleepers using low-moderate nocturnal caffeine (3 mg/kg).