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Stress, fatigue et troubles du sommeil : un trio sociétal moderne ? Daniel Neu, M.D. Laboratoire du Sommeil & Unité de Chronobiologie U78 Cycle Eli-Lilly.

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Presentation on theme: "Stress, fatigue et troubles du sommeil : un trio sociétal moderne ? Daniel Neu, M.D. Laboratoire du Sommeil & Unité de Chronobiologie U78 Cycle Eli-Lilly."— Presentation transcript:

1 Stress, fatigue et troubles du sommeil : un trio sociétal moderne ? Daniel Neu, M.D. Laboratoire du Sommeil & Unité de Chronobiologie U78 Cycle Eli-Lilly « Le stress dans tous ses états » 14 Mars 2011

2 Evolutions sociétales versus adaptations évolutives … ? … une question sur la comparaison dinégalités au niveau des vitesses ! Surcharge dinformations (overflow) Exigences de limmédiateté ?

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4 Keyword search (recherche mots-clés): Fatigue, Stress, Sleep Google (1 AND) : 7.300.000 Youtube : 451 (& 2820 pour fatigue AND stress) Google (2,, ) : 10.600 Pubmed (NIH) : 589 (dont 147 articles de revue !)

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6 Stress Fatigue Troubles du sommeil Liens… ? Directionalités…Causalités (étiopathogenèse)…Réciprocités

7 Epidémiologies Cliniques Réflexions Plan…

8 En Belgique : Plaintes de sommeil non-récupérateur : 38 % Plaintes de sommeil non-récupérateur : 38 % Plaintes de fatigue anormale et intense : 34 % Plaintes de fatigue anormale et intense : 34 %

9 Fatigue et sommeil : population générale [1] Le Bon O, Neu D, Verbanck P, Linkowski P. Relationships between sleepiness, fatigue, affective symptoms and non-restorative sleep complaints. Sleep 2008;31(Suppl):221 [2] Neu D, et al. Do sleepy and tired go together? Neuroepidemiology 2010;35:1–11 Pop. N = 150 [1] & [2]

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11 Prévalences de linsomnie Linsomnie (transitoire, intermittente ou chronique) est lun des troubles les plus courants du SNC; elle affecte environ 1/3 de la population générale. La prévalence de linsomnie est plus élevée chez les femmes que chez les hommes; environ 2/3 des patients sont des femmes. La prévalence de linsomnie augmente avec lâge. Weyerer and Dilling, Sleep.1991 Oct;14(5):392-8

12 Prévalences de linsomnie..suite 1. Weyerer and Dilling, Sleep.1991 Oct;14(5):392-8 2. Le Bon O, Neu D. et al. Sleep 2008;31(Suppl):221 Prévalence augment avec lâge

13 CHU Brugmann, Clinique du Stress, Service de Psychiatrie, Université Libre de Bruxelles (U.L.B.) Parmi les patients stressés, la fatigue est de loin le symptôme le plus fréquent : 75,8 % Parmi les patients stressés, la fatigue est de loin le symptôme le plus fréquent : 75,8 % la dyssomnie avec éveil matinal précoce vient en 2e position : 62 % la dyssomnie avec éveil matinal précoce vient en 2e position : 62 %

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15 S & F differentiation abilities …? Mairesse O, Neu D. Individual differences in the integration of homeostatic and circadian factors in sleepiness judgments. (Short, long and midrange sleepers) Sleep 2008;31(Suppl):53 Neu D, Cluydts R, et al. Clinical semantics, semiology and auto- evaluation. The challenging case of fatigue and sleepiness. Eur Neuropsychopharmacol. 2009; 19(S3): 346 Mairesse O, Neu D, Vandersmissen R, Cluydts R. Fatigue, sleepiness and sleep quality perception, in day, night and shift workers. BASS Autumn meeting 2008 Le Bon O, Neu D, et al. Sleep 2008;31(Suppl):221

16 discrimination abilities …? Neu D, Mairesse O, et al. An inconvenient truth about sleepiness: bad sleepers discriminate better fatigue from sleepiness than good sleepers J Sleep Res 2010; 19(Suppl 2): 179

17 Definitions de concepts... 1) Neu D, Mairesse O, Hoffmann G, et al. Do sleepy and tired go together? Neuroepidemiology 2010;35:1–11 2) Neu D, Linkowski P, Le Bon O. Clinical complaints of daytime sleepiness and fatigue: How to distinguish and treat them, especially when they are 'excessive' or 'chronic'? Acta Neurologica 2010; 110(1): 15-25 Sleepiness Sleepiness : trigger signal for spontaneous onset of sleep. Physiological phenomenon depending on previous sleep (S) and occurring at regular intervals following circadian (C) rhythms (two process model). In pathological conditions excessive daytime sleepiness (EDS) can be irrepressible. Sleepiness is best described by sleep propensity (1,2). Fatigue Fatigue : generally a condition in which maintaining of motor or mental energy level gets more difficult with duration of exercise (1,2). Fatigue needs rest not sleep to recover from. Comprendre la fatigue ?

18 sleepiness Excessive daytime sleepiness (EDS) associated with - sleep fragmentation or - sleep loss due to - a PSD (excepted insomnia) or - external factors. best described as a higher sleep propensity usually resolves with sleep. Fatigue Fatigue (clinical symptom) associated with - faster decrease of performance levels following a given motor or mental activity task. - many systemic medical conditions (including MDD) in all cases, directly or indirectly related to the CNS. Altered sleep quality seems to worsen fatigue states or contribute to its maintenance. Sleep disorders such as insomnia also classically present with daytime complaints of fatigue Invalidating fatigue, which interferes significantly with major daytime functions, must be chronic by nature and definition. leads more rapidly to a state of exhaustion and needs higher (increased) amounts of rest to recover from.

19 Sleepiness : Functional Modelization Borbély AA, 1982. A two process model of sleep regulation. Hum Neurobiology 1(3): 195-204

20 Neu D. et al. Clinical semantics, semiology and auto-evaluation. The challenging case of fatigue and sleepiness. Eur Neuropsychopharmacol. 2009; 19(S3): 346 Fatigue : Functional Modelization ? F1 : anti-homeostatic ?? F2 : circadian component(s) ?? [intensity of fatigue] [time of day] Wake up

21 intersections… impairments associated to both phenomena Attentional deficits, Vigilance, Concentration Performances depending upon the level/intesity of stimuli(s)..better if high stimulation Performances not depending upon stimuli level/intensity..less if higher stimulation SF Neu D, Kajosch H, Peigneux P, Verbanck P, et al. Cognitive impairment in fatigue and sleepiness associated conditions. Psychiatry Research, 2010 (in press)

22 Intersections…& relations Neu D. et al. Sleep quality perception in the chronic fatigue syndrome. Neuropsychobiology 2007; 56: 40-46 Neu D. et al. Qualité du sommeil : perceptions subjectives et observations objectives. Quels liens entre psychologie et physiologie? LEncéphale 2009;35:6 Neu D. & Mairesse O. Fatigue, sleepiness and sleep quality perception, in day, night and shift workers. BASS Meeting 2008 « sleep quality »? S F Subjective quality ?? Objective quality ?

23 Discrimination abilities ….TRD study of psychomotor and cognitive function in tt resist MDD Neu D, Kornreich C, Montana X, Hoffmann G, Sentissi O, Verbanck P. Cognitive impairment and altered vigilance in treatment-resistant depression. European Psychiatry 2010; 25(S1): 299

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25 Pharmacol Ther. 2011 Immune system to brain signaling: Neuropsychopharmacological implications. Capuron L, Miller AH. The immune system can influence the brain and behavior at any level. In the context of inflammation, pro-inflammatory cytokines that can access the CNS and interact with a cytokine network in the brain to influence virtually every aspect of brain function relevant to behavior including neurotransmitter metabolism, neuroendocrine function, synaptic plasticity, and neurocircuits that regulate mood, motor activity, motivation, anxiety and alarm. Behavioral consequences of these effects of the immune system on the brain include depression, anxiety, fatigue, psychomotor slowing, anorexia, cognitive dysfunction and sleep impairment; symptoms that overlap with those which characterize neuropsychiatric disorders, especially depression. Pathways that appear to be especially important in immune system effects on the brain include the cytokine signaling molecules, p38 mitogen-activated protein kinase and nuclear factor kappa B; indoleamine 2,3 dioxygenase and its downstream metabolites, kynurenine, quinolinic acid and kynurenic acid; the neurotransmitters, serotonin, dopamine and glutamate; and neurocircuits involving the basal ganglia and anterior cingulate cortex. A series of vulnerability factors including aging and obesity as well as chronic stress also appears to interact with immune to brain signaling to exacerbate immunologic contributions to neuropsychiatric disease.

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27 Etude du sommeil…polysomnographie ? α – δ sleep (intrusion dactvités EEG veille ds le SLP) CAP (cyclic alternating pattern, motifs EEG récurrents…) idiopathic micro-arousals (éveils inconscients ultracourts sans cause objectivable) REM deficiency (diminution du %) delayed REMS onset (latence dapparition SP allongée)

28 Neu D, Verbanck P, Linkowski P, Le Bon O. Fatigue, sleepiness, sleep quality and their relationships to affective symptom intensity in sleep-disordered patients. European Psychiatry 2010; 25(Suppl 1): 1445 Can PSG contribute to distinguish between F & S ? …. « yes we can ?! » Total absolute power over complete TIB (N=330)

29 too much love will kill you.. SWS =>Sleepiness SWS=>Fatigue ? Brian May, 1988 a desperate try of quantitative compensation for a qualitative altered function..?

30 unpublished data …mapping fatigue ? About SWA deficits and alpha-intrusion less energy in (ultra-)low range frequencies …and more in high frequency ranges..despite higher SWS duration …and absolute similar coherences vindication of alpha-delta sleep

31 Evolutions sociétales versus adaptations évolutives … ? … une question sur la comparaison dinégalités au niveau des vitesses ! ? Surcharge dinformations (overflow) Exigences de limmédiateté

32 the future directions… 4 Axes : 1.Expansions to other clinical models (MS, PR, HIV, Lymphoma, MDD, insomnia, narcolepsy, HI, sleep deprivations.. 2.Pre-clinical models (murine forced swim test vs sleep deprivation, hypocaloric intakes vs sleep restriction..) 3.Functional neuroimaging (fatiguability tasks vs sleep restriction 4.Molecular genetics, cellular energy metabolism, broader investigations of neurotransmitter turnovers and of differential cytokine activations

33 Laboratoire du Sommeil & Unité de Chronobiologie U78 CHU Brugmann U.L.B. Daniel Neu, Guy Hoffmann, Monique Kentos, Axelle Ransquin, Luc Stulens, Fatiha Mebarka, Marleen Bocken, Philippe Dupont, Paul Verbanck

34 Linsomnie – classification étiologique & temporelle (durée des symptômes) primaire : insomnie qui nest pas attribuable à une maladie physique, une maladie mentale ou une cause environnementale connue mais qui est caractérisée par une série constante de symptômes ; aussi dite psycho-physiologique secondaire (co-morbide): insomnie qui est un symptôme résultant dune maladie (physique ou mentale) existante transitoire : causée par excitation ou stress; peut ne durer que qqs nuits Intermittente: associée à un stress persistant ou une maladie; jusquà 21 jours Chronique: souvent une association de facteurs comprenant des troubles physiques et mentaux; au moins 1 mois. Linsomnie primaire est un trouble chronique (>1 mois) Quest-ce que linsomnie? ….suite DSM IV-TR & ICSD

35 1)Ramsawh HJ, Stein MB, et al. Relationship of anxiety disorders, sleep quality, and functional impairment. J Psychiatr Res. 2009 Jul;43(10):926-33. 2)Monti JM, Monti D. Sleep disturbance in generalized anxiety disorder and its treatment. Sleep Med Rev. 2000 Jun;4(3):263-276. 3)Harvey AG, Stinson K, et al. The subjective meaning of sleep quality: a comparison of individuals with and without insomnia. Sleep. 2008 Mar 1;31(3):383-93. Relations étroites (qualité du sommeil, sensation de récupération diurne, fatigue), réciproques (bi-directionnels), probablement en partie étiopathogéniques (vulnérabilités communes ? ; facteurs déclenchants communs ?) ou du moins physiopathologiques (liens physio et neurobio discutés), ayant des impacts cliniques et thérapeutiques importantes : orientation thérapeutique, qualité de vie, symptômes associés, risques associés, choix des traitements… (1,2,3)


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