Diclofenac plasma protein binding: PK-PD modelling in cardiac patients submitted to cardiopulmonary bypass

Twenty-four surgical patients of both sexes without cardiac, hepatic, renal or endocrine dysfunctions were divided into two groups: 10 cardiac surgical patients submitted to myocardial revascularization and cardiopulmonary bypass (CPB), 3 females and 7 males aged 65 ± 11 years, 74 ± 16 kg body weight, 166 ± 9 cm height and 1.80 ± 0.21 m2 body surface area (BSA), and control, 14 surgical patients not submitted to CPB, 11 female and 3 males aged 41 ± 14 years, 66 ± 14 kg body weight, 159 ± 9 cm height and 1.65 ± 0.16 m2 BSA (mean ± SD). Sodium diclofenac (1 mg/kg, im Voltaren 75® twice a day) was administered to patients in the Recovery Unit 48 h after surgery. Venous blood samples were collected during a period of 0-12 h and analgesia was measured by the visual analogue scale (VAS) during the same period. Plasma diclofenac levels were measured by high performance liquid chromatography. A two-compartment open model was applied to obtain the plasma decay curve and to estimate kinetic parameters. Plasma diclofenac protein binding decreased whereas free plasma diclofenac levels were increased five-fold in CPB patients. Data obtained for analgesia reported as the maximum effect (EMAX) were: 25% VAS (CPB) vs 10% VAS (control), P<0.05, median measured by the visual analogue scale where 100% is equivalent to the highest level of pain. To correlate the effect versus plasma diclofenac levels, the EMAX sigmoid model was applied. A prolongation of the mean residence time for maximum effect (MRTEMAX) was observed without any change in lag-time in CPB in spite of the reduced analgesia reported for these patients, during the time-dose interval. In conclusion, the extent of plasma diclofenac protein binding was influenced by CPB with clinically relevant kinetic-dynamic consequences

The mental health of graduate students at the Federal University of São Paulo: a preliminary report

We present data regarding the care provided to graduate level health professionals at the mental health center of the Federal University of São Paulo. From September 1996 to September 2003, 146 graduate students (99 in the Master's degree program and 47 in the Doctoral program) were attended. This population was predominantly female (68.5%), with a mean (± SD) age of 28.6 ± 4.42 years, not married (71.9%). Most of the subjects were professionals who had not graduated from the Federal University (78.1%). The students who sought help for psychological and/or psychiatric problems were classified into two categories: situational-adaptive crises and psychopathological crises. The main diagnoses were depression and anxiety disorders (44%) causing 4.5% of the subjects to be temporarily suspended from their graduate studies; 19.2% reported that they had used psychotropic drugs within the previous month, and 47.9% referred to sleep disturbances. Suicidal tendencies were mentioned by 18% of those interviewed. Students with emotional disturbances and academic dysfunctions should be recognized at an early stage, and it is fundamental for them to have access to mental health programs that provide formal, structured and confidential care. Thus, it is important that professors and advisors in graduate programs build a warm and affective learning environment. If we consider the expressive growth in Brazilian scientific production resulting from the implementation of an extensive national system of graduate education, it is important to focus efforts on enhancing and upgrading the mental health care system.

Hereditary motor and autonomic neuronopathy 1 maps to chromosome 20q13.2-13.3

The spinal muscular atrophies (SMA) or hereditary motor neuronopathies result from the continuous degeneration and death of spinal cord lower motor neurons, leading to progressive muscular weakness and atrophy. We describe a large Brazilian family exhibiting an extremely rare, late-onset, dominant, proximal, and progressive SMA accompanied by very unusual manifestations, such as an abnormal sweating pattern, and gastrointestinal and sexual dysfunctions, suggesting concomitant involvement of the autonomic nervous system. We propose a new disease category for this disorder, `hereditary motor and autonomic neuronopathy', and attribute the term, `survival of motor and autonomic neurons 1' (SMAN1) to the respective locus that was mapped to a 14.5 cM region on chromosome 20q13.2-13.3 by genetic linkage analysis and haplotype studies using microsatellite polymorphic markers. This locus lies between markers D20S120 and D20S173 showing a maximum LOD score of 4.6 at D20S171, defining a region with 33 known genes, including several potential candidates. Identifying the SMAN1 gene should not only improve our understanding of the molecular mechanisms underlying lower motor neuron diseases but also help to clarify the relationship between motor and autonomic neurons.

Lapsen neurologinen tutkiminen Touwenin menetelmällä

Opinnäytetyön tarkoituksena oli tehdä ohjekirja Touwenin testistä. Touwenin testin avulla voidaan tehdä laaja-alainen ja yksityiskohtainen neurologinen tutkimus lapselle. Tutkimus kohdistuu erityisesti lieviin neurologisiin poikkeavuuksiin (Minor Neurological Dysfunctions, MND). Tulosten avulla lapset jaotellaan neurologisesti normaaleihin, lievästi poikkeaviin (Simple MND), merkittävästi poikkeaviin (Complex MND) ja CP-vammaa sairastaviin lapsiin. Tutkittavia osa-alueita ovat asento ja lihasjänteys, refleksit, tahattomat liikkeet, koordinaatio ja tasapaino, hienomotoriikka, liitännäisliikkeet, tuntoaisti ja aivohermojen toiminta. Lasten hermosto on nopeasti kehittyvä ja laadullisesti erilainen kuin aikuisilla, sillä lapsen neurologinen kehitys on vielä kesken. Tämä täytyy huomioida lapsen neurologisessa tutkimuksessa ja tulosten tulkinnassa. Touwenin testi on suunnattu erityisesti 4-13-vuotiaille lapsille. Motoriset vaikeudet voivat vaikuttaa fyysiseen ja sosiaaliseen aktiivisuuteen sekä mielenterveyteen. Monesti niillä on yhteys myös oppimis- ja käytöshäiriöihin. Motorisen kehityksen merkittävät häiriöt olisi tärkeä löytää mahdollisimman varhain, jotta näiden lasten kehitystä voitaisiin tukea. Motorisia toimintahäiriöitä on huomattavasti enemmän lapsilla, jotka ovat syntyneet ennen raskausviikkoa 32 ja joiden syntymäpaino on alhainen. Tämän vuoksi keskosten neurologisen kehityksen seuranta on erityisen tärkeää.

Male gonadal function, prolactin secretion and lactotroph population in an experimental model of cirrhosis

Liver cirrhosis, a highly prevalent chronic disease, is frequently associated with endocrine dysfunctions, notably in the gonadal axis. We evaluated lactotroph population by immunohistochemistry, gonadotropins and prolactin by immunoradiometric assay and testosterone and estradiol by radioimmunoassay in adult male Wistar rats with cirrhosis induced by carbon tetrachloride. No significant difference in mean ± SEM percentages of lactotrophs was found between cirrhotic animals and controls (N = 12, mean 18.95 ± 1.29%). Although there was no significant difference between groups in mean serum levels of prolactin (control: 19.2 ± 4 ng/mL), luteinizing hormone (control: 1.58 ± 0.43 ng/mL), follicle-stimulating hormone (control: 19.11 ± 2.28 ng/mL), estradiol (control: 14.65 ± 3.22 pg/mL), and total testosterone (control: 138.41 ± 20.07 ng/dL), 5 of the cirrhotic animals presented a hormonal profile consistent with hypogonadism, all of them pointing to a central origin of this dysfunction. Four of these animals presented high levels of estradiol and/or prolactin, with a significant correlation between these two hormones in both groups (r = 0.54; P = 0.013). It was possible to detect the presence of central hypogonadism in this model of cirrhotic animals. The hyperestrogenemia and hyperprolactinemia found in some hypogonadal animals suggest a role in the genesis of hypogonadism, and in the present study they were not associated with lactotroph hyperplasia.

Pharmacology and toxicology of diphenyl diselenide in several biological models

The pharmacology of synthetic organoselenium compounds indicates that they can be used as antioxidants, enzyme inhibitors, neuroprotectors, anti-tumor and anti-infectious agents, and immunomodulators. In this review, we focus on the effects of diphenyl diselenide (DPDS) in various biological model organisms. DPDS possesses antioxidant activity, confirmed in several in vitro and in vivo systems, and thus has a protective effect against hepatic, renal and gastric injuries, in addition to its neuroprotective activity. The activity of the compound on the central nervous system has been studied since DPDS has lipophilic characteristics, increasing adenylyl cyclase activity and inhibiting glutamate and MK-801 binding to rat synaptic membranes. Systemic administration facilitates the formation of long-term object recognition memory in mice and has a protective effect against brain ischemia and on reserpine-induced orofacial dyskinesia in rats. On the other hand, DPDS may be toxic, mainly because of its interaction with thiol groups. In the yeast Saccharomyces cerevisiae, the molecule acts as a pro-oxidant by depleting free glutathione. Administration to mice during cadmium intoxication has the opposite effect, reducing oxidative stress in various tissues. DPDS is a potent inhibitor of d-aminolevulinate dehydratase and chronic exposure to high doses of this compound has central effects on mouse brain, as well as liver and renal toxicity. Genotoxicity of this compound has been assessed in bacteria, haploid and diploid yeast and in a tumor cell line.

Reduced folate carrier 1 (RFC1) is associated with cleft of the lip only

In this report, we have reanalyzed genotyping data in a collection of families from South America based on maternal origin. Genotyping analysis was performed at the Craniofacial Anomalies Research Center at the University of Iowa. These genotypes were derived from genomic DNA samples obtained from blood spots from children born with isolated orofacial clefts in 45 hospitals located in eight countries (Argentina, Bolivia, Brazil, Chile, Ecuador, Paraguay, Uruguay, and Venezuela) collaborating with ECLAMC (Latin American Collaborative Studies of Congenital Malformations) between January 1998 and December 1999. Dried blood samples were sent by regular mail to the Laboratory of Congenital Malformations, Federal University of Rio de Janeiro. Previous findings suggested that mitochondrial haplotype D is more commonly found among cleft cases born in South America. We hypothesized that association of certain genes may depend upon the ethnic origin, as defined by population-specific markers. Therefore, we tested if markers in MTHFR (5,10-methylenetetrahydrofolate reductase) and RFC1 (reduced folate carrier 1) were associated with oral clefts, depending on the maternal origin defined by the mitochondrial haplotype. Transmission distortion of alleles in MTHFR C677T and RFC1 G80A polymorphic variants was tested in 200 mother/affected child pairs taking into consideration maternal origin. RFC1 variation was over-transmitted to children born with cleft lip only (P = 0.017) carrying mitochondrial DNA haplotypes other than haplotype D. Our results provide a new indication that variation in RFC1 may contribute to cleft lip only. Future studies should investigate the association between oral clefts and RFC1 based on more discrete phenotypes.

Learning about brain physiology and complexity from the study of the epilepsies

The brain is a complex system, which produces emergent properties such as those associated with activity-dependent plasticity in processes of learning and memory. Therefore, understanding the integrated structures and functions of the brain is well beyond the scope of either superficial or extremely reductionistic approaches. Although a combination of zoom-in and zoom-out strategies is desirable when the brain is studied, constructing the appropriate interfaces to connect all levels of analysis is one of the most difficult challenges of contemporary neuroscience. Is it possible to build appropriate models of brain function and dysfunctions with computational tools? Among the best-known brain dysfunctions, epilepsies are neurological syndromes that reach a variety of networks, from widespread anatomical brain circuits to local molecular environments. One logical question would be: are those complex brain networks always producing maladaptive emergent properties compatible with epileptogenic substrates? The present review will deal with this question and will try to answer it by illustrating several points from the literature and from our laboratory data, with examples at the behavioral, electrophysiological, cellular and molecular levels. We conclude that, because the brain is a complex system compatible with the production of emergent properties, including plasticity, its functions should be approached using an integrated view. Concepts such as brain networks, graphics theory, neuroinformatics, and e-neuroscience are discussed as new transdisciplinary approaches dealing with the continuous growth of information about brain physiology and its dysfunctions. The epilepsies are discussed as neurobiological models of complex systems displaying maladaptive plasticity.

Increased levels of glutamate in the central nervous system are associated with behavioral symptoms in experimental malaria

Cerebral malaria (CM) is a severe complication resulting from Plasmodium falciparum infection. This condition has been associated with cognitive, behavioral and motor dysfunctions, seizures and coma. The underlying mechanisms of CM are incompletely understood. Glutamate and other metabolites such as lactate have been implicated in its pathogenesis. In the present study, we investigated the involvement of glutamate in the behavioral symptoms of CM. Seventeen female C57BL/6 mice (20-25 g) aged 6-8 weeks were infected with P. berghei ANKA by the intraperitoneal route using a standardized inoculation of 10(6) parasitized red blood cells suspended in 0.2 mL PBS. Control animals (N = 17) received the same volume of PBS. Behavioral and neurological symptoms were analyzed by the SmithKline/Harwell/Imperial College/Royal Hospital/Phenotype Assessment (SHIRPA) battery. Glutamate release was measured in the cerebral cortex and cerebrospinal fluid of infected and control mice by fluorimetric assay. All functional categories of the SHIRPA battery were significantly altered in the infected mice at 6 days post-infection (dpi) (P ≤ 0.05). In parallel to CM symptoms, we found a significant increase in glutamate levels in the cerebral cortex (mean ± SEM; control: 11.62 ± 0.90 nmol/mg protein; infected at 3 dpi: 10.36 ± 1.17 nmol/mg protein; infected at 6 dpi: 26.65 ± 0.73 nmol/mg protein; with EGTA, control: 5.60 ± 1.92 nmol/mg protein; infected at 3 dpi: 6.24 ± 1.87 nmol/mg protein; infected at 6 dpi: 14.14 ± 0.84 nmol/mg protein) and in the cerebrospinal fluid (control: 128 ± 51.23 pmol/mg protein; infected: 301.4 ± 22.52 pmol/mg protein) of infected mice (P ≤ 0.05). These findings suggest a role of glutamate in the central nervous system dysfunction found in CM.

Sleep pattern and learning in knockdown mice with reduced cholinergic neurotransmission

Impaired cholinergic neurotransmission can affect memory formation and influence sleep-wake cycles (SWC). In the present study, we describe the SWC in mice with a deficient vesicular acetylcholine transporter (VAChT) system, previously characterized as presenting reduced acetylcholine release and cognitive and behavioral dysfunctions. Continuous, chronic ECoG and EMG recordings were used to evaluate the SWC pattern during light and dark phases in VAChT knockdown heterozygous (VAChT-KDHET, n=7) and wild-type (WT, n=7) mice. SWC were evaluated for sleep efficiency, total amount and mean duration of slow-wave, intermediate and paradoxical sleep, as well as the number of awakenings from sleep. After recording SWC, contextual fear-conditioning tests were used as an acetylcholine-dependent learning paradigm. The results showed that sleep efficiency in VAChT-KDHET animals was similar to that of WT mice, but that the SWC was more fragmented. Fragmentation was characterized by an increase in the number of awakenings, mainly during intermediate sleep. VAChT-KDHET animals performed poorly in the contextual fear-conditioning paradigm (mean freezing time: 34.4±3.1 and 44.5±3.3 s for WT and VAChT-KDHET animals, respectively), which was followed by a 45% reduction in the number of paradoxical sleep episodes after the training session. Taken together, the results show that reduced cholinergic transmission led to sleep fragmentation and learning impairment. We discuss the results on the basis of cholinergic plasticity and its relevance to sleep homeostasis. We suggest that VAChT-KDHET mice could be a useful model to test cholinergic drugs used to treat sleep dysfunction in neurodegenerative disorders.

Expression of MMP-2 and MMP-9 in the rat trigeminal ganglion during the development of temporomandibular joint inflammation

Orofacial pain is a prevalent symptom in modern society. Some musculoskeletal orofacial pain is caused by temporomandibular disorders (TMDs). This condition has a multi-factorial etiology, including emotional factors and alteration of the masticator muscle and temporomandibular joints (TMJs). TMJ inflammation is considered to be a cause of pain in patients with TMD. Extracellular proteolytic enzymes, specifically the matrix metalloproteinases (MMPs), have been shown to modulate inflammation and pain. The purpose of this investigation was to determine whether the expression and level of gelatinolytic activity of MMP-2 and MMP-9 in the trigeminal ganglion are altered during different stages of temporomandibular inflammation, as determined by gelatin zymography. This study also evaluated whether mechanical allodynia and orofacial hyperalgesia, induced by the injection of complete Freund's adjuvant into the TMJ capsule, were altered by an MMP inhibitor (doxycycline, DOX). TMJ inflammation was measured by plasma extravasation in the periarticular tissue (Evans blue test) and infiltration of polymorphonuclear neutrophils into the synovial fluid (myeloperoxidase enzyme quantification). MMP expression in the trigeminal ganglion was shown to vary during the phases of the inflammatory process. MMP-9 regulated the early phase and MMP-2 participated in the late phase of this process. Furthermore, increases in plasma extravasation in periarticular tissue and myeloperoxidase activity in the joint tissue, which occurred throughout the inflammation process, were diminished by treatment with DOX, a nonspecific MMP inhibitor. Additionally, the increases of mechanical allodynia and orofacial hyperalgesia were attenuated by the same treatment.

Molecular patterns behind immunological and metabolic alterations in lysinuric protein intolerance

Lysinuric protein intolerance (LPI) is a recessively inherited disorder characterised by reduced plasma and increased urinary levels of cationic amino acids (CAAs), protein malnutrition, growth failure and hyperlipidemia. Some patients develop severe immunological, renal and pulmonary complications. All Finnish patients share the same LPIFin mutation in the SLC7A7 gene that encodes CAA transporter y+LAT1. The aim of this study was to examine molecular factors contributing to the various symptoms, systemic metabolic and lipid profiles, and innate immune responses in LPI. The transcriptomes, metabolomes and lipidomes were analysed in whole-blood cells and plasma using RNA microarrays and gas or liquid chromatography-mass spectrometry techniques, respectively. Toll-like receptor (TLR) signalling in monocyte-derived macrophages exposed to pathogens was scrutinised using qRT-PCR and the Luminex technology. Altered levels of transcripts participating in amino acid transport, immune responses, apoptosis and pathways of hepatic and renal metabolism were identified in the LPI whole-blood cells. The patients had increased non-essential amino acid, triacylglycerol and fatty acid levels, and decreased plasma levels of phosphatidylcholines and practically all essential amino acids. In addition, elevated plasma levels of eight metabolites, long-chain triacylglycerols, two chemoattractant chemokines and nitric oxide correlated with the reduced glomerular function in the patients with kidney disease. Accordingly, it can be hypothesised that the patients have increased autophagy, inflammation, oxidative stress and apoptosis, leading to hepatic steatosis, uremic toxicity and altered intestinal microbe metabolism. Furthermore, the LPI macrophages showed disruption in the TLR2/1, TLR4 and TLR9 pathways, suggesting innate immune dysfunctions with an excessive response to bacterial infections but a deficient viral DNA response.

Why budget accountability fails? The elusive links between parliaments and audit agencies in the oversight of the budget

ABSTRACTParliaments and audit agencies have critical and complementary roles in the oversight of the budget and the enforcement of government accountability. Yet, the nexus between parliaments and audit agencies is one of the weakest links in the accountability chain, generating an accountability gap in the budget process. This articles analyses the interactions between parliaments and audit agencies in the oversight of government finances during the latter stages of the budget process. Using proxies to evaluate the quality of those linkages, such as the follow-up to audit findings and the discharge of government, it shows important dysfunctions in the interactions between parliaments and audit agencies due to a combination of technical capacity constraints and political economy disincentives. It suggests that the effective functioning of the system of checks and balances in public budgeting critically hinges on the agility of the linkages between accountability institutions. As such, the failure of budget accountability is due to systemic dysfunctions in the systems of accountability, rather than the failure of an individual accountability institution acting in isolation. In addition, the effectiveness of the horizontal accountability architecture depends on the political economy incentives shaping the budget process, which are generated by the interactions between the choice of institutional design and budget rules, with the degree of political competition and electoral rules.

Pour une Église-communauté-de-paix dans un contexte multiethnique conflictuel : le cas du Cameroun

L’effervescence religieuse et politique au Cameroun engendre progressivement la fragmentation ethnique du peuple chrétien camerounais. Face à la manipulation politique, l’autre nom de l’injustice ethnique, la plupart des Camerounais et Camerounaises y compris les chrétiens réagissent désormais par le tribalisme, l’autre nom de la résignation ou mieux du déchirement social. Les Camerounais et Camerounaises donnent l’impression d’avoir perdu l’esprit de résistance/dissidence qui leur a valu la liberté ou mieux l’indépendance. Comment ignorer que de s’accoutumer au drame de la dérive ethnique, en s’installant, pour des raisons de survie, dans l’éclatement le plus abject, c’est opter pour l’asservissement volontaire d’un peuple qui mène inexorablement au génocide collectif ? Notre recherche repose sur l’hypothèse que les conflits ethniques ont pénétré la sphère du christianisme et font désormais partie des dysfonctionnements de l’Église du Cameroun. Ces dysfonctionnements internes nuisent à la crédibilité de l’Église. Il y a un lien entre les défaillances observées dans l’Église et les défaillances de la société Camerounaise. De plus, le rapport de convergence entre les rivalités ethniques et la religion, provoque un questionnement théologique inévitable : comment amener les différentes ethnies qui forment la plupart des États africains à un harmonieux vivre - ensemble inspiré par le mode de vie et de fonctionnement des Églises chrétiennes, au Cameroun en l'occurrence ? Faut-il se limiter à l’adoption d’une nouvelle image de l’Église par exemple l’Église-famille-de-Dieu, ou bien faut-il prendre le taureau par les cornes et éduquer les peuples africains à une culture de la paix ? La démarche de cette thèse s’inspire de la méthode adoptée par la théologie pratique, c’est-à-dire la praxéologie1, en relation avec la théologie contextuelle2, au niveau du lien avec les méthodes d’analyses des sciences sociales et sciences humaines, et au niveau de sa dimension prophétique créatrice. Elle est construite autour de quatre coordonnées: observation (médiation sociale), interprétation (médiation herméneutique), intervention pastorale (médiation pratique) et prospective. 1 Cf. G. ROUTHIER, et M.VIAU, (dir.), Précis de théologie pratique, Montréal/Bruxelles, Novalis/Lumen Vitae, 2004, 819 p. 2 Cf. C. BOFF, Théorie et pratique . La méthode des théologies de la libération, Paris, Cerf, 1990, 400 p. ii La thèse comporte quatre parties. La première partie (chapitres 1, 2 et 3) consacrée à l’observation cerne la problématique du vivre ensemble multiethnique, pour permettre de mieux percevoir la manifestation du phénomène du tribalisme dans l’Église (les Églises) et la société camerounaise. Elle montre que des situations dramatiques, de malheurs, de pauvreté, de famine, de conflits et de guerres sont causées en partie par le tribalisme exclusif. La deuxième partie (chapitres 4 et 5) porte sur la question du sens. Elle analyse et met à l’épreuve la compréhension du phénomène du tribalisme et des conflits ethniques dans la société et dans les Églises du Cameroun. Sont ainsi abordés, successivement, les principales articulations du tribalisme, la stratégie mise sur pied (diviser pour mieux régner) pour la transformation des structures sociales au Cameroun pendant la colonisation, puis récupérée par les politiciens comme idéologie politique depuis les indépendances. Nous en sommes arrivés à constater que cette idéologie a conduit à une profonde déstructuration de la société camerounaise jusque dans l’Église (les Églises). La troisième partie (chapitres 6 et 7) est consacrée à la pratique ecclésiale du dialogue de la diversité ethnique africaine pour la paix ; nous y montrons comment les solidarités ethniques purifiées au feu de l’Évangile peuvent avoir une influence sur la pratique chrétienne. Nous cherchons ensuite à démontrer que le dialogue interethnique bien articulé est le chemin de la réconciliation. La quatrième partie (chapitre 8) est un effort pour passer de l’utopie mise en pratique à une pratique en forme d’utopie. Nous cherchons à montrer que le dialogue pastoral enrichi par la diversité ethnique et religieuse entraînera la transformation de l’Église locale dans son interaction avec les différentes ethnies du Cameroun et d’Afrique.

Le sommeil des personnes atteintes de schizophrénie : résultats d’études par questionnaire, polysomnographie et analyse spectrale de l’EEG en sommeil paradoxal

Les personnes atteintes de schizophrénie peuvent présenter un sommeil anormal même lorsqu’elles sont stables cliniquement sous traitements pharmacologiques. Les études présentées dans cette thèse ont pour but de mesurer le sommeil afin de mieux comprendre les dysfonctions des mécanismes cérébraux pouvant être impliqués dans la physiopathologie de la schizophrénie. Les trois études présentées dans cette thèse rapportent des résultats sur le sommeil dans la schizophrénie à trois niveaux d’analyse chez trois groupes différents de patients. Le premier niveau est subjectif et décrit le sommeil à l’aide d’un questionnaire administré chez des personnes atteintes de schizophrénie cliniquement stables sous traitements pharmacologiques. Le deuxième niveau est objectif et évalue le sommeil par une méta-analyse des études polysomnographiques chez des patients atteints de schizophrénie ne recevant pas de traitement pharmacologique. Le troisième niveau est micro-structurel et utilise l’analyse spectrale de l’électroencéphalogramme (EEG) afin de caractériser le sommeil paradoxal de patients en premier épisode aigu de schizophrénie avant le début du traitement pharmacologique. La première étude montre que, lorsqu’évaluées par un questionnaire de sommeil, les personnes atteintes de schizophrénie cliniquement stables sous traitements pharmacologiques rapportent prendre plus de temps à s’endormir, se coucher plus tôt et se lever plus tard, passer plus de temps au lit et faire plus de siestes comparativement aux participants sains. Aussi, tout comme les participants sains, les personnes atteintes de schizophrénie rapportent un nombre normal d’éveils nocturnes, se disent normalement satisfaites de leur sommeil et se sentent normalement reposées au réveil. La deuxième étude révèle qu’objectivement, lorsque les études polysomnographiques effectuées chez des patients non traités sont soumises à une méta-analyse, les personnes atteintes de schizophrénie montrent une augmentation du délai d’endormissement, une diminution du temps total en sommeil, une diminution de l’efficacité du sommeil et une augmentation de la durée des éveils nocturnes comparativement aux participants sains. Les patients en arrêt aigu de traitement ont des désordres plus sévères au niveau de ces variables que les patients jamais traités. Seulement les patients jamais traités ont une diminution du pourcentage de stade 2 comparativement aux participants sains. La méta-analyse ne révèle pas de différence significative entre les groupes en ce qui concerne le sommeil lent profond et le sommeil paradoxal. La troisième étude, portant sur l’analyse spectrale de l’EEG en sommeil paradoxal, montre une diminution de l’amplitude relative de la bande de fréquence alpha dans les régions frontales, centrales et temporales et montre une augmentation de l’amplitude relative de la bande de fréquence bêta2 dans la région occipitale chez les personnes en premier épisode de schizophrénie jamais traitées comparativement aux participants sains. L’activité alpha absolue est positivement corrélée aux symptômes négatifs dans les régions frontales, centrales et temporales et négativement corrélée aux symptômes positifs dans la région occipitale. L’activité beta2 absolue ne montre pas de corrélation significative avec les symptômes positifs et négatifs de la schizophrénie. Ces résultats sont discutés suivant la possibilité que des dysfonctions au niveau des mécanismes de la vigilance seraient impliquées dans la physiopathologie de la schizophrénie.