Exploring the neurophysiological underpinnings of objective short sleep duration as a distinct subtype of insomnia disorder

Abstract

Insomnia is the most common sleep disorder, entailing a significant cost to society and to the individual. It is believed to be a highly heterogeneous disorder, but, to date, clinically reliable subtypes have been difficult to establish and treatments have remained generic. Insomnia with objective short sleep duration (ISSD) (total sleep time <6h measured by polysomnography (PSG) or actigraphy) was proposed as a distinct subtype in 1998, and a significant amount of literature has emerged, associating it with higher morbidity and mortality. As a biomarker for insomnia disorder, objective short sleep duration (SSD), as currently proposed, has limitations. PSG is costly and not widely available; a single night PSG may not reflect habitual sleep time as persons with insomnia show significant variability in sleep durations from night to night. SSD may reflect underlying pathophysiology of sleep but it is not a direct reflection, unlike the sleep spindle which is a neurophysiological hallmark of non-rapid eye movement sleep (NREM sleep). The overarching objective of this thesis was to explore objective SSD and its neurophysiological correlates to see whether it can define reliably a distinct subtype for insomnia disorder. In the first chapters of this thesis, I conducted a systematic review and meta-analysis of the ISSD subtype and its association with cardiovascular, endocrine and cognitive outcomes. This thesis reports the first meta-analytic data associating ISSD with higher risk Type II diabetes mellitus (T2DM) and hypertension (HTN). The first paper used a case control design with a small sample of patients with traumatic brain injury (N= 24) to determine that insomnia disorder was associated with a higher incidence of somatoform symptoms and stress compared to persons with obstructive sleep apnoea and hypersomnolence. The second paper utilised an innovative automatic spindle algorithm to examine sleep spindle activity in 168 participants. Lower fast spindle density in central and parietal regions was associated with the ISSD subtype compared to persons with insomnia with normal sleep duration (INSD). Furthermore, modest significant correlations were found between fast spindle density in frontal and central regions and longer total grand mean execution time (TGMT) on the Tower of London (TOL) test for executive functioning. However, TOL scores did not differ between participants divided according to objective short sleep duration. In the third paper, in a cohort of 96 participants, neither spindle density nor objective short sleep duration was associated with significant changes in insomnia severity index (ISI) scores at 16-weeks following a six-week course of cognitive behavioural therapy for insomnia (CBT I) delivered via a digital platform. The overall finding of the thesis was that objective short sleep duration does seem to define a subgroup of individuals with insomnia disorder with measurable neurophysiological differences on PSG. However, there are significant limitations to using objective sleep duration as a biomarker for insomnia disorder. It has been challenging to find meaningful subtypes in insomnia disorder. However, subtyping insomnia disorder may lead to insights into insomnia’s neurobiology, its clinical consequences and holds the promise of more effective, tailored treatments. The ISSD subtype has been effective in refocusing interest on the neurobiology of insomnia disorder yet has limitations. A neurophysiological characteristic of sleep, such as the sleep spindle, may contribute to more sophisticated models that reflect insomnia’s complexity.