Neurobehavioural performance in primary insomnia and healthy individuals: role of circadian rhythms, prior sleep and psychological well-being

Abstract

Despite growing awareness that the daytime impairments associated with insomnia are among its most disabling symptoms, they are poorly understood and in particular, the cognitive deficits remain inadequately characterised. Following a review of the insomnia literature, and based on the evidence that the circadian system may have a causative role in insomnia, it was concluded that circadian factors have not been adequately addressed in studies investigating the cognitive deficits associated with insomnia. Prior to investigating whether cognitive testing scheduled in the early evening could account for some of the discrepancy seen in past research, it was necessary to investigate the extent to which performance in healthy controls is influenced by the circadian system at this time of day. The aim of study one was therefore to investigate whether neurobehavioural performance is influenced by the Wake Maintenance Zone (WMZ), a time in the early evening when the circadian system promotes alertness. Thirty-one healthy young adults (8 F; 18 – 29 years) completed an inpatient laboratory study which consisted of a baseline day (8 hr sleep:16 hr wake) and a ~50 h constant routine (CR) protocol. Plasma melatonin was sampled every 30-60 minutes and subjects completed a comprehensive neurobehavioural test battery every 60-120 minutes. Performance in the three hours before the onset of melatonin synthesis (i.e., the expected WMZ) was compared to performance during a three hour block earlier in the day and it was determined that performance improved during the expected WMZ. These results confirmed that circadian phase is a major contributor to daytime functioning and demonstrated a clear need to consider time of day effects when investigating the objective performance deficits in insomnia patients. Particularly because in many previous studies performance testing may have coincided with the Wake Maintenance Zone. The aim of study two was therefore to compare the cognitive performance of patients with insomnia to healthy controls under controlled laboratory conditions using a protocol which addressed time of day effects. Fifty individuals diagnosed with primary insomnia (29 F, 37.04  12.35 years (M  SD) and 20 healthy good-sleepers (14 F, 34.75  12.05 years) completed at least 7 days of at home sleep-wake reporting and a set of subjective daytime dysfunction questionnaires, before attending a ~12 hour afternoon/evening laboratory visit. During this visit, all events were scheduled relative to each participants habitual bedtime and a modified constant posture protocol was followed. Participants provided saliva samples every 30 to 60 minutes. They also completed a comprehensive neurobehavioural test battery every 60 to 180 minutes including tasks measuring sustained and switching attention, working memory, as well as subjective measures of sleepiness, effort and mood, and a single driving simulator task. Compared to the control group, the insomnia group was shown to exhibit significantly slower performances on a switching attention task and a working memory task, but performances on a simple and a complex task of sustained attention were comparable between the groups. Exploratory analysis showed significant associations between neurobehavioural performance and self-reported depression, fatigue and insomnia severity in the insomnia patients but not the control group. No relationship between sleepiness or prior sleep duration and cognitive performance was present in the insomnia group. In the third study, circadian phase information was incorporated in the analysis comparing insomnia patients and controls. The circadian timing (DLMO) of the insomnia group and control group were comparable, however the insomnia group demonstrated a large range of phase angle difference (between habitual bedtime and DLMO) than the control group. When DLMO or phase angle difference were statistically controlled the insomnia group continued to show significant impairment on working memory and switching attention tasks, with performance on sustained attention tasks preserved relative to controls. Correlation analysis revealed associations between phase angle difference and the daytime (neurobehavioural performance, depression, fatigue and insomnia severity) and night time (sleep onset latency) symptoms of insomnia patients. No such pattern was seen in the control group. Together, the results of study two and three provide evidence for higher level cognitive deficits in patients with insomnia, and suggest that daytime performance is not associated with sleepiness or prior sleep disturbance, but is associated with symptoms such as fatigue, depression, quality of life, as well as circadian factors. These findings challenge the assumption that the daytime functional impairments of insomnia stem simply and directly from the chronic sleep disturbance, and instead provide evidence that the impairments result from multiple factors. Underscoring the important contribution that the circadian system makes to the pathophysiology and daytime symptoms of insomnia, these results provide evidence for a potential new avenue of treatment for some patients with insomnia.