Shantha M. W. Rajaratnam

Sleep disturbance and melatonin levels following traumatic brain injury

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 ± 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.

Disturbances in melatonin secretion and circadian sleep–wake regulation in Parkinson disease

OBJECTIVEnUsing salivary dim light melatonin onset (DLMO) and actigraphy, our study sought to determine if Parkinson disease (PD) patients demonstrate circadian disturbance compared to healthy controls. Additionally, our study investigated if circadian disturbances represent a disease-related process or may be attributed to dopaminergic therapy.nnnMETHODSnTwenty-nine patients with PD were divided into unmedicated and medicated groups and were compared to 27 healthy controls. All participants underwent neurologic assessment and 14 days of actigraphy to establish habitual sleep-onset time (HSO). DLMO time and area under the melatonin curve (AUC) were calculated from salivary melatonin sampling. The phase angle of entrainment was calculated by subtracting DLMO from HSO. Overnight polysomnography (PSG) was performed to determine sleep architecture.nnnRESULTSnDLMO and HSO were not different across the groups. However, the phase angle of entrainment was more than twice as long in the medicated PD group compared to the unmedicated PD group (U = 35.5; P = .002) and was more than 50% longer than controls (U = 130.0; P = .021). The medicated PD group showed more than double the melatonin AUC compared to the unmedicated group (U = 31; P = 0.001) and controls (U = 87; P = .001). There was no difference in these measures comparing unmedicated PD and controls.nnnCONCLUSIONSnIn PD dopaminergic treatment profoundly increases the secretion of melatonin. Our study reported no difference in circadian phase and HSO between groups. However, PD patients treated with dopaminergic therapy unexpectedly showed a delayed sleep onset relative to DLMO, suggesting dopaminergic therapy in PD results in an uncoupling of circadian and sleep regulation.

Actigraphic Assessment of Sleep Disturbances following Traumatic Brain Injury

The current study examined the use of actigraphy in measurement of sleep following traumatic brain injury (TBI). Twenty-one patients with TBI and self-reported sleep and/or fatigue problems and 21 non-injured controls were studied over seven days using actigraphy and sleep diary reports. Although strong associations between diary and actigraphic assessment of sleep duration were observed in both participant groups, agreement between these methods appeared to weaken in patients with TBI. Associations between sleep diary and actigraphic assessments of sleep disturbance, i.e., wake after sleep onset (WASO) and sleep onset latency (SOL) were not apparent in either group, although weaker agreement between methods for WASO was again observed in patients with TBI. Actigraphy may prove useful to supplement self-report measures of sleep following TBI. More work is required to understand the accuracy of these measures in this population.

Circadian Melatonin Rhythm Following Traumatic Brain Injury.

Background: Sleep-wake disturbances are highly prevalent following traumatic brain injury (TBI), impeding rehabilitaion and quality of life. However, the mechanisms underlying these sleep disturnbances are unclear, and efficacious treatments are lacking. To investigate possible mechanisms underlying sleep disturbance in TBI, we examined characteristics of the circadian rhythm of melatonin, a hormone involved in sleep-wake regulation. We compared TBI patients reporting sleep disturbance with age- and gender-matched healthy volunteers. Methods: We conducted an overnight observational study with salivary melatonin samples collected hourly in 9 patients with severe TBI and 9 controls. Salivary dim light melatonin onset (DLMO) as well as melatonin synthesis onset (SynOn) and offset (SynOff) were used to determine circadian timing. Total overnight salivary melatonin production was calculated as the area under the curve from melatonin synthesis onset to offset. Results: Compared with healthy individuals, TBI patients showed 42% less melatonin production overnight (d = 0.87; P = .034). The timing of DLMO was delayed by approximately 1.5 hours in patients with TBI compared with controls (d = 1.23; P = .003). Conclusions: In patients with TBI, melatonin production was attenuated overnight, and the timing of melatonin secretion was delayed. We suggest that disruption to the circadian regulation of melatonin synthesis is a feature of severe TBI, possibly contributing to the sleep difficulties that are commonly reported in this population.

Sleep Disturbances in Traumatic Brain Injury: A Meta-Analysis.

STUDY OBJECTIVESnSleep disturbances are frequently reported following traumatic brain injury (TBI); however, the exact disturbances remain unclear. This meta-analysis aimed to characterize sleep disturbance in community dwelling patients with TBI as compared to controls.nnnMETHODSnTwo investigators independently conducted a systematic search of multiple electronic databases from inception to May 27, 2015. Studies were selected if they compared sleep in community dwelling individuals with TBI relative to a control population without head injury. Data were pooled in meta-analysis with outcomes expressed as the standard mean difference (SMD) and 95% confidence interval (CI). The primary outcomes were derived from polysomnography and secondary outcomes were derived from subjective sleep measures.nnnRESULTSnSixteen studies were included, combining 637 TBI patients and 567 controls, all of whom were community dwelling. Pooled polysomnography data revealed that TBI patients had poorer sleep efficiency (SMD = -0.47, CI: -0.89, -0.06), shorter total sleep duration (SMD = -0.37, CI: -0.59, -0.16), and greater wake after sleep onset time (SMD = 0.60, CI: 0.33, 0.87). Although sleep architecture was similar between the groups, a trend suggested that TBI patients may spend less time in REM sleep (SMD = -0.22, CI: -0.45, 0.01). Consistent with polysomnographic derangement, TBI patients reported greater subjective sleepiness and poorer perceived sleep quality.nnnCONCLUSIONSnThe evidence suggests that TBI is associated with widespread objective and subjective sleep deficits. The present results highlight the need for physicians to monitor and address sleep deficits following TBI.

Cognitive Behavior Therapy to Treat Sleep Disturbance and Fatigue After Traumatic Brain Injury: A Pilot Randomized Controlled Trial

OBJECTIVEnTo evaluate the efficacy of adapted cognitive behavioral therapy (CBT) for sleep disturbance and fatigue in individuals with traumatic brain injury (TBI).nnnDESIGNnParallel 2-group randomized controlled trial.nnnSETTINGnOutpatient therapy.nnnPARTICIPANTSnAdults (N=24) with history of TBI and clinically significant sleep and/or fatigue complaints were randomly allocated to an 8-session adapted CBT intervention or a treatment as usual (TAU) condition.nnnINTERVENTIONSnCognitive behavior therapy.nnnMAIN OUTCOME MEASURESnThe primary outcome was the Pittsburgh Sleep Quality Index (PSQI) posttreatment and at 2-month follow-up. Secondary measures included the Insomnia Severity Index, Fatigue Severity Scale, Brief Fatigue Inventory (BFI), Epworth Sleepiness Scale, and Hospital Anxiety and Depression Scale.nnnRESULTSnAt follow-up, CBT recipients reported better sleep quality than those receiving TAU (PSQI mean difference, 4.85; 95% confidence interval [CI], 2.56-7.14). Daily fatigue levels were significantly reduced in the CBT group (BFI difference, 1.54; 95% CI, 0.66-2.42). Secondary improvements were significant for depression. Large within-group effect sizes were evident across measures (Hedges g=1.14-1.93), with maintenance of gains 2 months after therapy cessation.nnnCONCLUSIONSnAdapted CBT produced greater and sustained improvements in sleep, daily fatigue levels, and depression compared with TAU. These pilot findings suggest that CBT is a promising treatment for sleep disturbance and fatigue after TBI.

Intoxication and criminal behaviour

The common law position in Australia in relation to self‐induced intoxication and criminal responsibility is that evidence of intoxication should be taken into account when determining whether the Crown has proved beyond reasonable doubt that an accused person acted voluntarily and intentionally. In the Code jurisdictions, similar principles apply, although evidence of intoxication is generally only relevant to certain classes of offences. Although many legal commentaries on the issue of intoxication and criminal responsibility have been published in recent years, many of these have largely ignored the vast and rapidly growing scientific literature on the nature and effects of intoxication. This article describes the major effects of various psychoactive drugs, with particular emphasis on the potential effects of these drugs on criminal behaviour. The drugs are classified according to their major pharmacological properties — central nervous system depressants, central nervous system stimulants, opiates, cannabis, hallucinogens and anabolic steroids. The literature reviewed in this article suggests that the effects of intoxication on criminal behaviour may vary greatly depending on the type of drug that is taken and a number of situational factors. Therefore, it is considered inappropriate to deal with the law on intoxication and criminal responsibility with ‘blanket’ principles. Instead, each individual case of intoxication should be considered separately to determine whether the accuseds behaviour was likely to be a consequence of intoxication.

Prevalence of Circadian Misalignment and Its Association With Depressive Symptoms in Delayed Sleep Phase Disorder

Study ObjectivenTo examine the prevalence of circadian misalignment in clinically diagnosed delayed sleep phase disorder (DSPD) and to compare mood and daytime functioning in those with and without a circadian basis for the disorder.nnnMethodsnOne hundred and eighty-two DSPD patients aged 16-64 years, engaged in regular employment or school, underwent sleep-wake monitoring in the home, followed by a sleep laboratory visit for assessment of salivary dim light melatonin onset (DLMO). Based on the DLMO assessments, patients were classified into two groups: circadian DSPD, defined as DLMO occurring at or after desired bedtime (DBT), or non-circadian DSPD, defined as DLMO occurring before DBT.nnnResultsnOne hundred and three patients (57%) were classified as circadian DSPD and 79 (43%) as non-circadian DSPD. DLMO occurred 1.66 hours later in circadian DSPD compared to non-circadian DSPD (p < .001). Moderate-severe depressive symptoms (Beck Depression Inventory-II) were more prevalent in circadian DSPD (14.0%) than in non-circadian DSPD (3.8%; p < .05). Relative to non-circadian DSPD patients, circadian DSPD patients had 4.31 times increased odds of at least mild depressive symptoms (95% CI 1.75 to 10.64; p < .01). No group differences were found for daytime sleepiness or function, but DSPD symptoms were rated by clinicians to be more severe in those with circadian DSPD.nnnConclusionsnAlmost half of patients clinically diagnosed with DSPD did not show misalignment between the circadian pacemaker and the DBT, suggesting that the reported difficulties initiating sleep at the DBT are unlikely to be explained by the (mis)timing of the circadian rhythm of sleep propensity. Circadian misalignment in DSPD is associated with increased depressive symptoms and DSPD symptom severity.

Randomized, Prospective Study of the Impact of a Sleep Health Program on Firefighter Injury and Disability

Study ObjectivesnFirefighters schedules include extended shifts and long work weeks which cause sleep deficiency and circadian rhythm disruption. Many firefighters also suffer from undiagnosed sleep disorders, exacerbating fatigue. We tested the hypothesis that a workplace-based Sleep Health Program (SHP) incorporating sleep health education and sleep disorders screening would improve firefighter health and safety compared to standard practice.nnnDesignnProspective station-level randomized, field-based intervention.nnnSettingnUS fire department.nnnParticipantsn1189 firefighters.nnnInterventionsnSleep health education, questionnaire-based sleep disorders screening, and sleep clinic referrals for respondents who screened positive for a sleep disorder.nnnMeasurements and ResultsnFirefighters were randomized by station. Using departmental records, in an intention-to-treat analysis, firefighters assigned to intervention stations which participated in education sessions and had the opportunity to complete sleep disorders screening reported 46% fewer disability days than those assigned to control stations (1.4 ± 5.9 vs. 2.6 ± 8.5 days/firefighter, respectively; p = .003). There were no significant differences in departmental injury or motor vehicle crash rates between the groups. In post hoc analysis accounting for intervention exposure, firefighters who attended education sessions were 24% less likely to file at least one injury report during the study than those who did not attend, regardless of randomization (OR [95% CI] 0.76 [0.60, 0.98]; χ2 = 4.56; p = .033). There were no significant changes pre- versus post-study in self-reported sleep or sleepiness in those who participated in the intervention.nnnConclusionsnA firefighter workplace-based SHP providing sleep health education and sleep disorders screening opportunity can reduce injuries and work loss due to disability in firefighters.

Diagnosis, cause, and treatment approaches for delayed sleep-wake phase disorder

Delayed sleep-wake phase disorder (DSWPD) is commonly defined as an inability to fall asleep and wake at societal times resulting in excessive daytime sleepiness. Although the cause is multifaceted, delays in sleep time are largely driven by misalignment between the circadian pacemaker and the desired sleep-wake timing schedule. Current treatment approaches focus on correcting the circadian delay; however, there is a lack of data investigating combined therapies for treatment of DSWPD.