title: Circadian Melatonin Rhythm Following Traumatic Brain Injury.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: Department of Psychiatry, Harvard Medical School, MA, USA Department of Psychiatry, Beth Israel Deaconess Medical Center, MA, USA School of Psychological Sciences and Institute for Cognitive and Clinical Neurosciences, Monash University, VIC, Australia Monash-Epworth Rehabilitation Research Centre, VIC, Australia.
authors.forename: Natalie A
authors.initials: NA
authors.lastname: Grima
authors.affiliation: School of Psychological Sciences and Institute for Cognitive and Clinical Neurosciences, Monash University, VIC, Australia Monash-Epworth Rehabilitation Research Centre, VIC, Australia.
authors.forename: Jennie L
authors.initials: JL
authors.lastname: Ponsford
authors.affiliation: Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital, MA. USA Division of Sleep Medicine, Department of Medicine, Harvard Medical School, MA, USA.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: St Hilaire
authors.affiliation: School of Psychological Sciences and Institute for Cognitive and Clinical Neurosciences, Monash University, VIC, Australia Monash Lung and Sleep, Monash Health, VIC, Australia.
authors.forename: Darren
authors.initials: D
authors.lastname: Mansfield
authors.affiliation: School of Psychological Sciences and Institute for Cognitive and Clinical Neurosciences, Monash University, VIC, Australia Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital, MA. USA Division of Sleep Medicine, Department of Medicine, Harvard Medical School, MA, USA Shantha.rajaratnam@monash.edu.
authors.forename: Shantha M
authors.initials: SM
authors.lastname: Rajaratnam
mesh_terms: D000328:Adult; D019540:Area Under Curve; D000070642:Brain Injuries, Traumatic / Q000378:metabolism*; D016022:Case-Control Studies; D002940:Circadian Rhythm / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008550:Melatonin / Q000378:metabolism*; D008875:Middle Aged; D012463:Saliva / Q000378:metabolism; D055815:Young Adult
chemical_list: D008550:Melatonin
keywords: sleep; traumatic brain injury