The putative role of oxidative stress and inflammation in the pathophysiology of sleep dysfunction across neuropsychiatric disorders: Focus on chronic fatigue syndrome, bipolar disorder and multiple sclerosis - 07/08/18

Doi : 10.1016/j.smrv.2018.03.007

Gerwyn Morris ^a, Brendon Stubbs ^b,^c, Cristiano A. Köhler ^d, Ken Walder ^e, Anastasiya Slyepchenko ^f,^g, Michael Berk ^h,^i,^j, André F. Carvalho ^k,^l,^⁎
^a Tir Na Nog, Bryn Road Seaside 87, Llanelli, SA152LW, Wales, United Kingdom
^b Physiotherapy Department, South London and Maudsley NHS Foundation Trust, Denmark Hill, London, SE5 8AZ, United Kingdom
^c Health Service and Population Research Department, Institute of Psychiatry, Psychology and Neuroscience King's College London, De Crespigny Park, London, SE5 8AF, United Kingdom
^d Department of Clinical Medicine and Translational Psychiatry Research Group, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil
^e Deakin University, The Centre for Molecular and Medical Research, School of Medicine, P.O. Box 291, Geelong, 3220, Australia
^f Women's Health Concerns Clinic, St. Joseph's Healthcare Hamilton, 100 West 5th Street, Suite C124, Hamilton, ON, L8N 3K7, Canada
^g MiNDS Neuroscience Graduate Program, McMaster University, 1280 Main St. W., Hamilton, ON, Canada
^h Deakin University, IMPACT Strategic Research Centre, School of Medicine, Barwon Health, P.O. Box 291, Geelong, 3220, Australia
ⁱ Orygen Youth Health Research Centre and the Centre of Youth Mental Health, The Florey Institute for Neuroscience and Mental Health, University of Melbourne, Parkville, 3052, Australia
^j Department of Psychiatry, University of Melbourne, Parkville, 3052, Australia
^k Department of Psychiatry, University of Toronto, Toronto, ON, Canada
^l Centre for Addiction & Mental Health (CAMH), Toronto, ON, Canada

^∗Corresponding author.

Sous presse. Épreuves corrigées par l'auteur. Disponible en ligne depuis le Tuesday 07 August 2018

Summary

Sleep and circadian abnormalities are prevalent and burdensome manifestations of diverse neuro-immune diseases, and may aggravate the course of several neuropsychiatric disorders. The underlying pathophysiology of sleep abnormalities across neuropsychiatric disorders remains unclear, and may involve the inter-play of several clinical variables and mechanistic pathways. In this review, we propose a heuristic framework in which reciprocal interactions of immune, oxidative and nitrosative stress, and mitochondrial pathways may drive sleep abnormalities across potentially neuroprogressive disorders. Specifically, it is proposed that systemic inflammation may activate microglial cells and astrocytes in brain regions involved in sleep and circadian regulation. Activated glial cells may secrete pro-inflammatory cytokines (for example, interleukin-1 beta and tumour necrosis factor alpha), nitric oxide and gliotransmitters, which may influence the expression of key circadian regulators (e.g., the Circadian Locomotor Output Cycles Kaput (CLOCK) gene). Furthermore, sleep disruption may further aggravate oxidative and nitrosative, peripheral immune activation, and (neuro) inflammation across these disorders in a vicious pathophysiological loop. This review will focus on chronic fatigue syndrome, bipolar disorder, and multiple sclerosis as exemplars of neuro-immune disorders. We conclude that novel therapeutic targets exploring immune and oxidative & nitrosative pathways (p.e. melatonin and molecular hydrogen) hold promise in alleviating sleep and circadian dysfunction in these disorders.

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Keywords : Chronic fatigue syndrome, Bipolar disorder, Multiple sclerosis, Sleep, Inflammation, Oxidative stress