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Stress, fatigue et troubles du sommeil : un trio sociétal moderne ?

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Presentation on theme: "Stress, fatigue et troubles du sommeil : un trio sociétal moderne ?"— Presentation transcript:

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

2 Surcharge d’informations (‘overflow’) Exigences de l’immédiateté ?
Evolutions sociétales versus adaptations évolutives … ? … une question sur la comparaison d’inégalités au niveau des vitesses ! Surcharge d’informations (‘overflow’) Exigences de l’immédiateté ?

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

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

7 Plan… Epidémiologies Cliniques Réflexions

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

9 Fatigue et sommeil : population générale
Pop. N = 150 [1] & [2] [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

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

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

13 la dyssomnie avec éveil matinal précoce vient en 2e position : 62 %
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 % la dyssomnie avec éveil matinal précoce vient en 2e position : 62 %

14 So I will try to give you a quick overview of the progression of the investigated
tracks and their findings. As I just said, I had to start by seeing how much or how far I could separate both (F&S) regarding perception, discrimination abilities and relations to sleep. We chose at the beginning namely clinical conditions that are supposed to be preferentially related to either one of both concepts. But even then we found that, if we want to go further, we had to try to render things as pure as possible  quickly give results

15 S & F differentiation abilities …?
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 I’m sorry for the overload here, but I may quickly summarize these ideas. We were rapidly confronted with the fact that discrimination abilities were different among population samples. … Metaphorically spoken you could say that for example, for someone who was never been confronted to low back or neuropathic pain it is difficult to imagine what it feels like The same could in contrast to sleepiness (which has a physiological component) apply to chronic fatigue for instance. Do we all have similar abilities to differentiate between S & F … what does it depend on ? Semantic explanations only ? Or is there something else ? It seems as if certain conditions or repeated experience of sleep restriction may also rise the discriminative abilities in certain cases… Le Bon O, Neu D, et al. Sleep 2008;31(Suppl):221 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 Mairesse O, Neu D, Vandersmissen R, Cluydts R. Fatigue, sleepiness and sleep quality perception, in day, night and shift workers. BASS Autumn meeting 2008 15

16 discrimination abilities …?
When patients with high PSQI discriminated visibly better than “ good sleepers” … because they probably better know what chronic fatigue feels like (cf. pain) 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 Comprendre la fatigue ? Definitions de concepts...
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 : 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. It is often difficult for both patients and clinicians to distinguish the semiological notions of F&S although their potential physiopathological aspects and functional underpinnings can be very different. The main idea of all these upcoming slides is in fact first to contribute to a descriptive distinction by investigating separations, differences but also similarities in associated features to both F&S and second to investigate especially the unclear relations that fatigue has with sleep. 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 17

18 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. Excessive daytime sleepiness (EDS) associated with - sleep fragmentation or - sleep loss due to - a PSD (excepted insomnia) - external factors. best described as a higher sleep propensity usually resolves with sleep. This review in the Belgian Neurological Acta just summarizes the currently available data and conceptualizations & in the end we came up with the following distinctive state definitions … EXPLIQUER : - sleep fragmentation or relative deprivation  direct link link of CF to sleep seems to be at least of a more indirect nature and is mainly linked to systemic conditions (inflammatory process, infections, MDD, stress, etc.)

19 Sleepiness : Functional Modelization
Sleepiness as a concept has indeed already a physiological function with a genius modelization which is known by all of us. I would also like to thank our president from which I borrowed the smaller slide Borbély AA, A two process model of sleep regulation. Hum Neurobiology 1(3):

20 Fatigue : Functional Modelization ?
[intensity of fatigue] F1 : anti-homeostatic ?? F on the other hand, is not at all a unified concept and we still have no common ground for F, There is no universal objective measurement and no theoretical model. We have also no clear vision of the relationships between F and sleep, despite the fact that all patients with chronic daytime F express a systematic complaint of NRS or of unrefreshing sleep (for what ever this means …) F2 : circadian component(s) ?? [time of day] Wake up Neu D. et al. Clinical semantics, semiology and auto-evaluation. The challenging case of fatigue and sleepiness. Eur Neuropsychopharmacol. 2009; 19(S3): 346

21 intersections… impairments associated to both phenomena
F Performances depending upon the level/intesity of stimuli(s) ..better if high stimulation Attentional deficits, Vigilance, Concentration Performances not depending upon stimuli level/intensity ..less if higher stimulation 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
F Objective quality ? Subjective quality ?? « sleep quality »? The SAHS who does not complain about his sleep !! But we find SOMETHING The CFS patient who complains a lot and heavily about his sleep … and we do not find ANYTHING !! (or don’t we look at the right things !?) 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? L’Encéphale 2009;35:6 Neu D. & Mairesse O. Fatigue, sleepiness and sleep quality perception, in day, night and shift workers. BASS Meeting 2008

23 Discrimination abilities …
Discrimination abilities ….TRD study of psychomotor and cognitive function in tt resist MDD Same thing here with a study in TR MDD These patients, also in contrast to a non-clinical sample show very distinctive relations between fatigue and affective symptoms (high effect sizes top of left figure) and between S and affective symptoms (bottom of left figure : NS) Study with 17 TRD patients (two tt essais without remission) & 17 matched ctrls and 2 measure points, at a 2 week interva,l of cognitive function, psychometric data, vigilance assessments and affective symptoms intensity, 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.

26 ? ? Mais c’est quoi la “qualité” du sommeil ….?
Quelles sont les caractéristiques d’un sommeil « récupérateur » ..?

27 Etude du sommeil…polysomnographie ?
α – δ sleep (intrusion d’actvités 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 d’apparition SP ‘allongée’)

28 Can PSG contribute to distinguish between F & S ?
…. « yes we can ?! » Colin Shapiro from Toronto (current ed-in chief of the JPR) is certainly one of the central personalities that pushed a lot of keystone studies in the field of F & S investigations rising the awareness of the unadressed but necessary distinction as well as the lack of understanding concerning fatigue. So one of the most inspiring papers for me was this one… Total absolute power over complete TIB (N=330) 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

29 “too much love will kill you..”
Brian May, 1988 SWS => Sleepiness SWS => Fatigue ? a desperate try of quantitative compensation for a qualitative altered function ..? One could summarize several studies regarding sleep in CFS that we did and the available literature reviews on other chronic fatigue states like chronic infections (CFJD, HIV, HCV) with this provocative question. Another recurrent element would be the supposed frequent alteration of SWS with an alpha-like intrusion (phasic or tonic)

30 …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 However this must be kept secret because otherwise Pr Le Bon will cut my head off … this is a paper that we are currently submitting where we will be propose a different way to look at SWS or SWA in chronic fatigue and the respective energy levels of EEG spectral bands among electrode sites This is even more striking on the background that we found absolute similar coherence values after application of a linear modelization of power bands unpublished data

31 Surcharge d’informations (‘overflow’) Exigences de l’immédiateté
Evolutions sociétales versus adaptations évolutives … ? … une question sur la comparaison d’inégalités au niveau des vitesses ! ? Surcharge d’informations (‘overflow’) Exigences de l’immédiateté

32 the future directions… 4 Axes :
Expansions to other clinical models (MS, PR, HIV, Lymphoma, MDD, insomnia, narcolepsy, HI, sleep deprivations .. Pre-clinical models (murine forced swim test vs sleep deprivation, hypocaloric intakes vs sleep restriction..) Functional neuroimaging (fatiguability tasks vs sleep restriction Molecular genetics, cellular energy metabolism, broader investigations of neurotransmitter turnovers and of differential cytokine activations And for the next 5 to 10 years, I truly hope to develop these tracks to further improve our understanding of what the essence of any fatigue might possibly be and mostly how chronic fatigue relates to sleep … if it ever comes out that there really is any relationship of this kind !

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 Qu’est-ce que l’insomnie? ….suite
L’insomnie – classification étiologique & temporelle (durée des symptômes) primaire : insomnie qui n’est 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 d’une 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; jusqu’à 21 jours Chronique: souvent une association de facteurs comprenant des troubles physiques et mentaux; au moins 1 mois. L’insomnie primaire est un trouble chronique (>1 mois) DSM IV-TR & ICSD

35 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) Ramsawh HJ, Stein MB, et al. Relationship of anxiety disorders, sleep quality, and functional impairment. J Psychiatr Res Jul;43(10): Monti JM, Monti D. Sleep disturbance in generalized anxiety disorder and its treatment. Sleep Med Rev Jun;4(3): Harvey AG, Stinson K, et al. The subjective meaning of sleep quality: a comparison of individuals with and without insomnia. Sleep Mar 1;31(3):


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