title: When time stands still: an integrative review on the role of chronodisruption in posttraumatic stress disorder.
abstract: OBJECTIVE
  The human circadian system creates and maintains cellular and systemic rhythmicity essential to homeostasis. Loss of circadian rhythmicity fundamentally affects the neuroendocrine, immune and autonomic system, similar to chronic stress and, thus, may play a central role in the development of stress-related disorders. This article focuses on the role of circadian misalignment in the pathophysiology of posttraumatic stress disorder (PTSD).
  
  
  RESULTS
  Sleep disruption is a core feature of PTSD supporting the important supraordinate pathophysiological role of circadian system in PTSD. Furthermore, direct and indirect human and animal PTSD research suggests circadian system linked neuroendocrine, immune, metabolic and autonomic dysregulation with blunted diurnal rhythms, specific sleep pattern pathologies and cognitive deficits, as well as endocannabinoid and neuropeptide Y system alterations and altered circadian gene expression, linking circadian misalignment to PTSD pathophysiology.
  
  
  CONCLUSIONS
  PTSD development is associated with chronodisruption findings. Evaluation and treatment of sleep and circadian disruption should be the first steps in PTSD management. State-of-the-art methods of circadian rhythm assessment should be applied to bridge the gap between clinical significance and limited understanding of the relationship between traumatic stress, sleep and circadian system.
authors.affiliation: aDepartment of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany bVeterans Affairs Center of Excellence for Stress and Mental Health cDepartment of Psychiatry, University of California dVA San Diego Healthcare System, San Diego, California, USA eDepartment of Psychiatry and Psychotherapy, Charité University Medical Center, Campus Benjamin Franklin, Berlin, Germany.
authors.forename: Agorastos
authors.initials: A
authors.lastname: Agorastos
authors.forename: Michael
authors.initials: M
authors.lastname: Kellner
authors.forename: Dewleen G
authors.initials: DG
authors.lastname: Baker
authors.forename: Christian
authors.initials: C
authors.lastname: Otte
mesh_terms: D002940:Circadian Rhythm / Q000502:physiology*; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology; D010913:Pituitary-Adrenal System / Q000502:physiology; D020178:Sleep Disorders, Circadian Rhythm / Q000150:complications / Q000503:physiopathology*; D013313:Stress Disorders, Post-Traumatic / Q000209:etiology / Q000503:physiopathology*; D013315:Stress, Psychological / Q000503:physiopathology*