Sleep disturbance and melatonin levels following traumatic brain injury

School of Psychology and Psychiatry, Monash University, Victoria 3800, Australia.
Neurology (Impact Factor: 8.29). 05/2010; 74(21):1732-8. DOI: 10.1212/WNL.0b013e3181e0438b
Source: PubMed


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.
This was an observational study comparing 23 patients with TBI (429.7 +/- 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.
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.
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.


Available from: Jennie Ponsford, Feb 28, 2015
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    • "sleep recordings after chronic TBI show alterations in sleep architecture . Reports of sleep architecture vary , however , suggesting either lower percentage of sleep in non - rapid eye movement stage 2 ( NREM2 ) and REM ( Parcell et al . , 2008 ; Schreiber et al . , 2008 ) or a higher percentage of Slow Wave Sleep ( SWS ; Parcell et al . , 2008 ; Shekleton et al . , 2010 ; Sommerauer et al . , 2013 ) when compared to those without a history of TBI . Finally , alterations in spectral power , a measure of synaptic strength and synchronization , have also been found following injury ( Khoury et al . , 2013 ) . Atypical sleep architecture may exacerbate long - term cognitive deficits caused by injury , as sl"
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    ABSTRACT: Individuals with a history of traumatic brain injury (TBI) often report sleep disturbances, which may be caused by changes in sleep architecture or reduced sleep quality (greater time awake after sleep onset, poorer sleep efficiency, and sleep stage proportion alterations). Sleep is beneficial for memory formation, and herein we examine whether altered sleep physiology following TBI has deleterious effects on sleep-dependent declarative memory consolidation. Participants learned a list of word pairs in the morning or evening, and recall was assessed 12-hrs later, following an interval awake or with overnight sleep. Young adult participants (18-22 yrs) were assigned to one of four experimental groups: TBI Sleep (n=14), TBI Wake (n=12), non-TBI Sleep (n=15), non-TBI Wake (n=15). Each TBI participant was >1 yr post-injury. Sleep physiology was measured with polysomnography. Memory consolidation was assessed by comparing change in word-pair recall over 12-hr intersession intervals. The TBI group spent a significantly greater proportion of the night in SWS than the non-TBI group at the expense of NREM1. The TBI group also had marginally lower EEG delta power during SWS in the central region. Intersession changes in recall were greater for intervals with sleep than without sleep in both groups. However, despite abnormal sleep stage proportions for individuals with a TBI history, there was no difference in the intersession change in recall following sleep for the TBI and non-TBI groups. In both Sleep groups combined, there was a positive correlation between Intersession Change and the proportion of the night in NREM2 + SWS. Overall, sleep composition is altered following TBI but such deficits do not yield insufficiencies in sleep-dependent memory consolidation.
    Frontiers in Human Neuroscience 06/2015; 9. DOI:10.3389/fnhum.2015.00328 · 3.63 Impact Factor
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    • "Limited data are available in traumatic brain injury (TBI), demonstrating that melatonin secretion is markedly impaired in severe brain injury patients (Moskala et al., 2004; Paparrigopoulos et al., 2006; Shekleton et al., 2010). This study aimed to investigate the nocturnal melatonin levels and the integrity of the pathway regulating melatonin secretion, in particular the RHT, in VS patients by means of the melatonin suppression test by light. "
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    ABSTRACT: Circadian rhythms were recently proposed as a measure of physiological state and prognosis in disorders of consciousness (DOC). So far, melatonin regulation was never assessed in vegetative state (VS). Aim of our research was to investigate the nocturnal melatonin levels and light-induced melatonin suppression in a cohort of VS patients. We assessed six consecutive patients (four men, age 33.3 ± 9.3 years) with post-traumatic VS and nine age-matched healthy volunteers (five men, age 34.3 ± 8.9 years) on two consecutive nights: one baseline and one light exposure night. During baseline, night subjects were in bed in a dim (<5 lux) room from 10 pm to 8 am. Blood samples were collected hourly 00:30-3:30 am (00:30 = MLT1; 1:30 = MLT2; 2:30 = MLT3; and 3:30 = MLT4). Identical setting was used for melatonin suppression test night, except for the exposure to monochromatic (470 nm) light from 1:30 to 3:30 am. Plasma melatonin levels were evaluated by radioimmunoassay. Magnitude of melatonin suppression was assessed by melatonin suppression score (caMSS) and suppression rate. We searched for group differences in melatonin levels, differences between repeated samples melatonin concentrations during baseline night and light exposure night, and light-induced suppression of melatonin secretion. During baseline night, controls showed an increase of melatonin (MLT4 vs MLT1, p = 0.037), while no significant changes were observed in VS melatonin levels (p = 0.172). Baseline night MLT4 was significantly lower in VS vs controls (p = 0.036). During light-exposure night, controls displayed a significant suppression of melatonin (MLT3 and MLT4 vs MLT2, p = 0.016 and 0.002, respectively), while VS patients displayed no significant changes. The magnitude of light-induced suppression of melatonin levels was statistically different between groups considering control adjusted caMSS (p = 0.000), suppression rate (p = 0.002) and absolute percentage difference (p = 0.012). These results demonstrate for the first time that VS patients present an alteration in night melatonin secretion and reduced light-induced melatonin suppression. These findings confirm previous studies demonstrating a disruption of the circadian system in DOC and suggest a possible benefit from melatonin supplementation in VS.
    Chronobiology International 03/2014; 31(5). DOI:10.3109/07420528.2014.901972 · 3.34 Impact Factor
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    • "Series of studies from Baumann et al. revealed reduced number of hypothalamic hypocretin (orexin) neurons in patients who died of severe TBI, low and undetectable cerebrospinal fluid levels of hypocretin (orexin) in the acute period after TBI and an association between low hypocretion levels and posttraumatic sleepiness [14,35,36]. Apart from hypocretin (orexin), reduced evening melatonin production due to traumatic brain damage may be associated with disturbed sleep in TBI population [18]. TBI can cause a variety of brain injuries. "
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    ABSTRACT: Sleep disturbance is very common following traumatic brain injury (TBI), which may initiate or exacerbate a variety of co-morbidities and negatively impact rehabilitative treatments. To date, there are paradoxical reports regarding the associations between inherent characteristics of TBI and sleep disturbance in TBI population. The current study was designed to explore the relationship between the presence of sleep disturbance and characteristics of TBI and identify the factors which are closely related to the presence of sleep disturbance in TBI population. 98 TBI patients (72 males, mean age ± SD, 47 ± 13 years, range 18-70) were recruited. Severity of TBI was evaluated based on Glasgow Coma Scale (GCS). All participants performed cranial computed tomography and were examined on self-reported sleep quality, anxiety, and depression. TBI was mild in 69 (70%), moderate in 15 (15%) and severe in 14 (15%) patients. 37 of 98 patients (38%) reported sleep disturbance following TBI. Insomnia was diagnosed in 28 patients (29%) and post-traumatic hypersomnia in 9 patients (9%). In TBI with insomnia group, 5 patients (18%) complained of difficulty falling asleep only, 8 patients (29%) had difficulty maintaining sleep without difficulty in initial sleep and 15 patients (53%) presented both difficulty falling asleep and difficulty maintaining sleep. Risk factors associated with insomnia were headache and/or dizziness and more symptoms of anxiety and depression rather than GCS. In contrast, GCS was independently associated with the presence of hypersomnia following TBI. Furthermore, there was no evidence of an association between locations of brain injury and the presence of sleep disturbance after TBI. Our data support and contribute to a growing body of evidence which indicates that TBI patients with insomnia are prone to suffer from concomitant headache and/or dizziness, report more symptoms of anxiety and depression and severe TBI patients are likely to experience hypersomnia.
    PLoS ONE 10/2013; 8(10):e76087. DOI:10.1371/journal.pone.0076087 · 3.23 Impact Factor
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