Sleep disturbance and melatonin levels following traumatic brain injury

Abstract

Objectives: Sleep disturbances commonly follow traumatic brain injury (TBI) and contribute to ongoing disability. However, there are no conclusive findings regarding specific changes to sleep quality and sleep architecture measured using polysomnography. Possible causes of the sleep disturbances include disruption of circadian regulation of sleep-wakefulness, psychological distress, and a neuronal response to injury. We investigated sleep-wake disturbances and their underlying mechanisms in a TBI patient sample. Methods:This was an observational study comparing 23 patients with TBI (429.7 Ϯ 287.6 days post injury) and 23 age-and gender-matched healthy volunteers on polysomnographic sleep measures, salivary dim light melatonin onset (DLMO) time, and self-reported sleep quality, anxiety, and depression.Results: Patients with TBI reported higher anxiety and depressive symptoms and sleep disturbance than controls. Patients with TBI showed decreased sleep efficiency (SE) and increased wake after sleep onset (WASO). Although no significant group differences were found in sleep architecture, when anxiety and depression scores were controlled, patients with TBI showed higher amount of slow wave sleep. No differences in self-reported sleep timing or salivary DLMO time were found. However, patients with TBI showed significantly lower levels of evening melatonin production. Melatonin level was significantly correlated with REM sleep but not SE or WASO. Conclusions:Reduced evening melatonin production may indicate disruption to circadian regulation of melatonin synthesis. The results suggest that there are at least 2 factors contributing to sleep disturbances in patients with traumatic brain injury. We propose that elevated depression is associated with reduced sleep quality, and increased slow wave sleep is attributed to the effects of mechanical brain damage. Neurology ® 2010;74:1732-1738 GLOSSARY AUC ϭ area under the curve; DLMO ϭ dim light melatonin onset; EOG ϭ electrooculogram; ESS ϭ Epworth Sleepiness Scale; HADS ϭ Hospital Anxiety and Depression Scale; MEQ ϭ Morningness Eveningness Questionnaire; NREM ϭ non-REM; PSQI ϭ Pittsburgh Sleep Quality Index; PTA ϭ posttraumatic amnesia; SE ϭ sleep efficiency; SOL ϭ sleep onset latency; SWS ϭ slow wave sleep; TBI ϭ traumatic brain injury; WASO ϭ wake after sleep onset.Sleep disturbances are common following traumatic brain injury (TBI), reported by 30%-75% of individuals and contributing to ongoing disability.

Sleep, Sleep Disorders, and Mild Traumatic Brain Injury. What We Know and What We Need to Know: Findings from a National Working Group

“…Poor subjective sleep quality is one of the most common complaints of patients who have experienced mTBI, with milder injury being associated with greater impairments in both subjective and objective measures of sleep [22]. Furthermore, the incidence of sleep disorder diagnoses is greater in patients with mTBI than in the general population.…”

“…More specifically, patients with mTBI demonstrate increased sleep fragmentation, delayed sleep onset, increased awakenings and time awake during the night, and reduced sleep efficiency (e.g., [81]). Further, at least 3 studies have found that relative to matched healthy controls, patients with mixed-severity TBI demonstrate increased slow-wave sleep (SWS) [22,82], although another study found reduced SWS and lower NREM delta power [83]. In light of the regenerative effects of SWS (e.g., axonal sprouting and synaptic remodeling), these findings appear to suggest a potential role for SWS in recovery from TBI.…”

“…For example, mTBI is frequently associated with significant autonomic dysregulation and alterations in normal circadian patterns [53,78]. Head injuries and neurotrauma may affect normal melatonin production [22]. Alterations in melatonin production and secretion following TBI not only both promote and propagate circadian dysregulation and insomnia, but it might also portend worse outcomes as melatonin provides neuroprotective properties in animal models [97].…”

“…Similarly, acute changes that occur with brain injury impact cellular functions and neural microstructure, potentially causing cell death and more persistent changes in brain function, including increased sleep drive [12]. Other hypothesized shared mechanisms between sleep disturbance and TBI of varying severity, including mTBI, include impaired neurotransmitter function [54,[110][111][112], cerebrovascular autoregulatory dysfunction [113,114], neuroinflammation [115], and dysregulation of circadian hormones [22,116,117]. In addition, interactions between mTBI and comorbid conditions such as PTSD [118], polytrauma, and chronic pain [119], have received increasing attention in the literature.…”

Electrophysiologic Evaluation of Diffuse Axonal Injury after Traumatic Brain Injury

“…The degree of damage to sleep-wake regulating centers such as the ascending reticular formation and associated pathways or neurotransmitter systems affect sleep disturbances [10,11]. Anxiety and depression frequently occur after TBI, and increased depression is associated with decreased sleep quality [12,13].…”