Physiology, assessment, and disorders of the pupil.

Proper examination of the pupil provides an objective measure of the integrity of the pregeniculate afferent visual pathway and allows assessment of sympathetic and parasympathetic innervation to the eye. Infrared videography and pupillography are increasingly used to study the dynamic behavior of the pupil in common disorders, such as Horner's syndrome and tonic pupil.

Daytime sleepiness and the COMT val158met polymorphism in patients with Parkinson disease.

STUDY OBJECTIVE: A preliminary study by our group suggested an association between daytime sleepiness and the catechol-O-methyltransferase (COMT) val158met polymorphism (rs4680) in patients with Parkinson disease (PD). We sought to confirm this association in a large group of patients with PD. DESIGN: Genetic association study in patients with PD. SETTING: Movement disorder sections at 2 university hospitals. PARTICIPANTS: PD patients with and without episodes of suddenly falling asleep matched for antiparkinsonian medication, disease duration, sex, and age, who participated in a previous genetic study on dopamine-receptor polymorphisms. INTERVENTIONS: Not applicable. MEASUREMENTS AND RESULTS: In this study, 240 patients with PD (154 men; age 65.1 +/- 6.1 years; disease duration 9.4 +/- 6.0 years) were included. Seventy had the met-met (LL), 116 the met-val (LH), and 54 the val-val (HH) genotype. In the combined LL+LH group (featuring reduced COMT activity), the mean Epworth Sleepiness Scale (ESS) score was 9.0 +/- 5.9 versus 11.0 +/- 6.1 in the HH (high COMT activity) group (P = .047). Forty-seven percent of the LL and LH patients had sudden sleep onset compared with 61% of the HH patients (P = .07). Logistic regression, however, showed that both pathologic ESS scores (i.e., > 10) and sudden sleep onset were predicted by subjective disease severity (P < .001 each) but not by the COMT genotype. CONCLUSIONS: Our previous finding that the L-allele may be associated with daytime sleepiness could not be confirmed in the present study. Altogether, our data do not support a clinically relevant effect of the COMT genotype on daytime sleepiness in PD.

Analog circuit for real-time computation of respiratory mechanical impedance in sleep studies

The aim of this work was to develop a low-cost circuit for real-time analog computation of the respiratory mechanical impedance in sleep studies. The practical performance of the circuit was tested in six patients with obstructive sleep apnea. The impedance signal provided by the analog circuit was compared with the impedance calculated simultaneously with a conventional computerized system. We concluded that the low-cost analog circuit developed could be a useful tool for facilitating the real-time assessment of airway obstruction in routine sleep studies.

Médecine de l'adolescence : troubles des conduites alimentaires atypiques [Adolescent medicine : eating disorders not otherwise specified (EDNOS)]

Young people (mostly females) suffering from eating disorders not otherwise specified (EDNOS) are more and more numerous and their difficulties pose serious problems to health care providers as well as the society. These situations correspond to eating disorders which do not totally meet the DSM-IV criteria for either anorexia or bulimia nervosa. The duration of the symptoms, the extent of suffering as well as the impact on daily life should be taken into account to set-up the treatment. The therapeutic approach to these disorders should ideally include both cognitive/dietary and psychodynamic approaches. The Multidisciplinary Unit for Adolescent Health in Lausanne has set-up a group treatment for these patients.

Differential effects of sodium oxybate and baclofen on EEG, sleep, neurobehavioral performance, and memory.

STUDY OBJECTIVES: Sodium oxybate (SO) is a GABA(B) agonist used to treat the sleep disorder narcolepsy. SO was shown to increase slow wave sleep (SWS) and EEG delta power (0.75-4.5 Hz), both indexes of NREM sleep (NREMS) intensity and depth, suggesting that SO enhances recuperative function of NREM. We investigated whether SO induces physiological deep sleep. DESIGN: SO was administered before an afternoon nap or before the subsequent experimental night in 13 healthy volunteers. The effects of SO were compared to baclofen (BAC), another GABA(B) receptor agonist, to assess the role of GABA(B) receptors in the SO response. MEASUREMENTS AND RESULTS: As expected, a nap significantly decreased sleep need and intensity the subsequent night. Both drugs reversed this nap effect on the subsequent night by decreasing sleep latency and increasing total sleep time, SWS during the first NREMS episode, and EEG delta and theta (0.75-7.25 Hz) power during NREMS. The SO-induced increase in EEG delta and theta power was, however, not specific to NREMS and was also observed during REM sleep (REMS) and wakefulness. Moreover, the high levels of delta power during a nap following SO administration did not affect delta power the following night. SO and BAC taken before the nap did not improve subsequent psychomotor performance and subjective alertness, or memory consolidation. Finally, SO and BAC strongly promoted the appearance of sleep onset REM periods. CONCLUSIONS: The SO-induced EEG slow waves seem not to be functionally similar to physiological slow waves. Our findings also suggest a role for GABA(B) receptors in REMS generation. CITATION: Vienne J; Lecciso G; Constantinescu I; Schwartz S; Franken P; Heinzer R; Tafti M. Differential effects of sodium oxybate and baclofen on EEG, sleep, neurobehavioral performance, and memory. SLEEP 2012;35(8):1071-1084.

Role of major histocompatibility complex class II expression by non-hematopoietic cells in autoimmune and inflammatory disorders: facts and fiction.

It is well established that interactions between CD4(+) T cells and major histocompatibility complex class II (MHCII) positive antigen-presenting cells (APCs) of hematopoietic origin play key roles in both the maintenance of tolerance and the initiation and development of autoimmune and inflammatory disorders. In sharp contrast, despite nearly three decades of intensive research, the functional relevance of MHCII expression by non-hematopoietic tissue-resident cells has remained obscure. The widespread assumption that MHCII expression by non-hematopoietic APCs has an impact on autoimmune and inflammatory diseases has in most instances neither been confirmed nor excluded by indisputable in vivo data. Here we review and put into perspective conflicting in vitro and in vivo results on the putative impact of MHCII expression by non-hematopoietic APCs-in both target organs and secondary lymphoid tissues-on the initiation and development of representative autoimmune and inflammatory disorders. Emphasis will be placed on the lacunar status of our knowledge in this field. We also discuss new mouse models-developed on the basis of our understanding of the molecular mechanisms that regulate MHCII expression-that constitute valuable tools for filling the severe gaps in our knowledge on the functions of non-hematopoietic APCs in inflammatory conditions.

Fourth cranial nerve palsy and brown syndrome: two interrelated congenital cranial dysinnervation disorders?

Based on neuroimaging data showing absence of the trochlear nerve, congenital superior oblique palsy is now classified as a congenital cranial dysinnervation disorder. A similar absence of the abducens nerve is accompanied by misinnervation to the lateral rectus muscle from a branch of oculomotor nerve in the Duane retraction syndrome. This similarity raises the question of whether some cases of Brown syndrome could arise from a similar synkinesis between the inferior and superior oblique muscles in the setting of congenital superior oblique palsy. This hypothesis has gained support from the confluence of evidence from a number of independent studies. Using Duane syndrome as a model, we critically review the accumulating evidence that some cases of Brown syndrome are ultimately attributable to dysgenesis of the trochlear nerve.

Constructive thinking skills and impulsivity dimensions in conduct and substance use disorders: differences and relationships in an adolescents' sample.

Impact of conduct disorder (CD) and substance use disorder (SUD) on constructive thinking skills and impulsivity was explored. 71 offending adolescents were assessed for CD and SUD. Furthermore, the constructive thinking inventory, the immediate and delayed memory tasks and the UPPS impulsive behaviour scale were administered. Results showed that youths with CD, independently from SUD, presented higher personality impulsivity (urgency) and altered constructive thinking skills (categorical thinking and personal superstitious thinking). Furthermore, trait-impulsivity explained variation in constructive thinking skills. The implications of these results were discussed.

Ontogeny of Sleeping in Color - Linking melanism to sleep architecture and rhythmicity variation in wild barn owl nestlings

The function of sleep remains unknown. To gain insight into the function of sleep in natural conditions, I assessed variation in sleep architecture and its link with fitness-related phenotypic traits. I considered melanin-based coloration because its underlying genetic basis is very well known giving an opportunity to examine whether some genes pleiotropically regulate both coloration and sleep. The melanocortin system is known to generate covariation between melanin-based coloration and other phenotypes like behaviour, physiology and life history traits. I investigated whether this system of genes could participate in the co-expression of coloration and sleep. I carried out a study with nestling barn owls (Tyto alba) in order to tackle the potential link between variation in color traits and the ontogeny of sleep under natural conditions. For this I established a suitable method for recording the brain activity (electroencephalogram) of owls in nature. Birds are especially interesting, because they convergently evolved sleep states similar to those exhibited by mammals. As in mammals, I found that in owlets time spent in rapid eye movement (REM) sleep declines with age, a relationship thought to eflect developmental changes in the brain. Thus this developmental trajectory appears to reflect a fundamental feature of sleep. Additionally, I discovered an association between a gene involved in melanism expressed in the feather follicles (proprotein convertase subtilisin/kexin type 2, PCSK2) and the age-related changes in sleep in the brain. Nestlings with higher expression levels of PCSK2 showed a more precocial pattern of sleep development and a higher degree of melanin-based coloration compared to nestlings with lower PCSK2 expression. Also sleep architecture and the development of rhythmicity in brain and physical activity was related to plumage traits of the nestlings and their biological parents. This pattern during ontogeny might reflect differences in life l history strategies, antipredator behaviour and developmental pace. Therefore, differently colored individuals may differentially deal with trade-offs between the costs and benefits of sleep which in turn lead to differences in brain organization and ultimately fitness. These results should stimulate evolutionary biologists to consider sleep as a major life history trait. Résumé La fonction du sommeil reste inconnue. Afin d'acquérir une meilleur compréhension de la fonction du sommeil dans les conditions naturelles, j'ai analysé la variation dans l'architecture du sommeil et son lien avec d'autres traits phénotypiques liés au succès reproducteur (fitness). J'ai choisi et examiné la coloration mélanique, car ses bases génétiques sont bien connues et il est ainsi possible d'étudier si certains gènes, de façon pléiotropique régulent à la fois la coloration et le sommeil. J'ai exploré si ce système génétique était impliqué dans la co-expression de la coloration et du sommeil. J'ai effectué mon étude sur des poussins de chouette effraie (Tyto alba) en condition naturelle, pour rechercher ce lien potentiel entre la variation de la coloration et l'ontogenèse du sommeil. Dans ce but, j'ai établi une méthodologie permettant d'enregistrer l'activité cérébrale (électroencéphalogramme) des chouettes dans la nature. Les oiseaux sont particulièrement intéressants car ils ont développé, par évolution convergente, des phases de sommeil similaires à celles des mammifères. De manière semblable à ce qui a été montré chez les mammifères, j'ai découvert que le temps passé dans le sommeil paradoxal diminue avec l'âge des poussins. On pense que ceci est dû aux changements développementaux au niveau du cerveau. Cette trajectoire développementale semble refléter une caractéristique fondamentale du sommeil. J'ai également découvert une association entre l'un des gènes impliqué dans le mélanisme, exprimé dans les follicules plumeux (proprotein convertase subtilisin/kexin type 2, PCSK2), et les changements dans la structure du sommeil avec l'âge. Les poussins ayant un niveau d'expression génétique élevé de la PCSK2 présentent une structure du sommeil plus précoce et un taux de coloration dû à la mélanine plus élevé que des poussins avec un niveau d'expression moindre de la PCSK2. L'architecture du sommeil et le développement de la rythmicité dans le cerveau ainsi que l'activité physique sont également liés à la coloration des plumes des poussins et pourraient ainsi refléter des différences de stratégies d'histoire de vie, de comportements anti-prédateur et de vitesses développementales. Ainsi, des individus de coloration différente sembleraient traiter différemment les coûts et les bénéfices du sommeil, ce qui aurait des conséquences sur l'organisation cérébrale et pour finir, sur le succès reproducteur. Ces résultats devraient encourager les biologistes évolutionnistes à considérer le sommeil comme un important trait d'histoire de vie. Zusammenfassung Die Funktion von Schlaf ist noch unbekannt. Um mehr Einsicht in diese unter natürlichen Bedingungen zu bekommen, habe ich die Variation in der Schlafarchitektur und die Verknüpfung mit phänotypischen Merkmalen, die mit der Fitness zusammenhängen, studiert. Ich habe mir melanin-basierte Färbung angesehen, da die zugrunde liegende genetische Basis bekannt ist und somit die Möglichkeit gegeben ist, zu untersuchen, ob einige Gene beides regulieren, Färbung und Schlaf. Das melanocortin System generiert eine Kovariation zwischen melanin-basierter Färbung und anderen phänotypischer Merkmale wie Verhalten, Physiologie und Überlebensstrategien. Ich habe untersucht, ob dieses Gensystem an einer gleichzeitigen Steuerung von Färbung und Schlaf beteiligt ist. Dazu habe ich Schleiereulen (Tyto alba) studiert um einen möglichen Zusammenhang zwischen der Variation in der Pigmentierung und der Entwicklung des Schlafs unter natürlichen Bedingungen zu entdecken. Für diese Studie entwickelte ich eine Methode um die Gehirnaktivität (Elektroenzephalogramm) bei Eulen in der Natur aufzunehmen. Vögel sind besonders interessant, da sie die gleichen Schlafstadien aufweisen wie Säugetiere und diese unabhängig konvergent entwickelt haben. Genauso wie bei Säugetieren nahm die Dauer des sogenannten ,,rapid eye movement" (REM) - Schlafes mit zunehmendem Alter ab. Es wird angenommen, dass dieser Zusammenhang die Entwicklung des Gehirns widerspiegelt. Daher scheint dieses Entwicklungsmuster ein fundamentaler Aspekt von Schlaf zu sein. Zusätzlich entdeckte ich einen Zusammenhang zwischen der Aktivität eines Gens in den Federfollikeln (proprotein convertase subtilisin/kexin type 2, PCSK2), das für die Ausprägung schwarzer Punkte auf den Federn der Eulen verantwortlich ist, und den altersabhängigen Änderungen im Schlafmuster im Gehirn. Küken mit höherer Aktivität von PCSK2 zeigten eine frühreifere Schlafentwicklung und eine dunklere Färbung als Küken mit niedriger PCSK2 Aktivität. Die Architekture des Schlafes und die Entwicklung der Rhythmik im Gehirn und die der physischen Aktivität ist mit der Färbung des Gefieders von den Küken und ihren Eltern verknüpft. Dieses Muster während der Entwicklung kann Unterschiede in Überlebensstrategien, Feindabwehrverhalten und in der Entwicklungsgeschwindigkeit reflektieren. Unterschiedlich gefärbte Individuen könnten unterschiedliche Strategien haben um zwischen den Kosten und Nutzen von Schlaf zu entscheiden, was zu Unterschieden in der Gehirnstruktur führen kann und letztendlich zur Fitness. Diese Ergebnisse sollten Evolutionsbiologen stimulieren Schlaf als einen wichtigen Bestandteil des Lebens zu behandeln.

Sleep and vigilance linked to melanism in wild barn owls.

Understanding the function of variation in sleep requires studies in the natural ecological conditions in which sleep evolved. Sleep has an impact on individual performance and hence may integrate the costs and benefits of investing in processes that are sensitive to sleep, such as immunity or coping with stress. Because dark and pale melanic animals differentially regulate energy homeostasis, immunity and stress hormone levels, the amount and/or organization of sleep may covary with melanin-based colour. We show here that wild, cross-fostered nestling barn owls (Tyto alba) born from mothers displaying more black spots had shorter non-REM (rapid eye movement) sleep bouts, a shorter latency until the occurrence of REM sleep after a bout of wakefulness and more wakefulness bouts. In male nestlings, the same sleep traits also correlated with their own level of spotting. Because heavily spotted male nestlings and the offspring of heavily spotted biological mothers switched sleep-wakefulness states more frequently, we propose the hypothesis that they could be also behaviourally more vigilant. Accordingly, nestlings from mothers displaying many black spots looked more often towards the nest entrance where their parents bring food and towards their sibling against whom they compete. Owlets from heavily spotted mothers might invest more in vigilance, thereby possibly increasing associated costs due to sleep fragmentation. We conclude that different strategies of the regulation of brain activity have evolved and are correlated with melanin-based coloration.

Impact on assertivity of a social skills training with adolescents suffering from psychotic or anxiety/mood disorders: An exploratory study

During adolescence numerous of important social abilities are acquired within interactions with peers. Severe psychiatric disorders interfere with the acquisition of these social skills. For example, due to excessive shyness, adolescents with psychiatric disorders may not experiment positive social interactions. Social skills training (SKT) may help adolescents to remediate to these diffi culties. This exploratory study aims to assess the SKT's effect on assertivity, in a population of adolescents presenting psychiatric disorder and attending a day care unit for adolescents. The SKT, delivered in group, deals with different themes such as contact, conversation, problem solving, confl ict, fail, success, learning, effort, separation, breakdown, and project. In this context, 38 adolescents (19 suffering from anxiety / mood disorder and 19 suffering from psychotic disorder) rate their level of assertivity before and after a SKT with the Rathus assertivity scale. This scale allows to differentiate between inhibited, assertive and assertiveaggressive adolescents. Results showed a general improvement on assertivity after the SKT. More specifi cally, adolescents suffering from anxiety disorder and the 'inhibited' adolescents showed the higher benefi t from the SKT. Thus, two hours per week of SKT seems to enhance social abilities in a population with severe psychiatric disorders. More specifi - cally, adolescents with anxiety / mood disorders reported more benefi ts of the SKT on their assertivity. Nevertheless, adolescents with psychotic disorders did not report strong benefi ts from the SKT despite the improvement observed at a clinical level. This observation raises questions about the usefulness of self-reported questionnaire to measure such benefi t for adolescents with psychosis.

Cellular perspectives on the glutamate-monoamine interactions in limbic lobe structures and their relevance for some psychiatric disorders.

Dopaminergic, serotonergic and noradrenergic nuclei form the trimonoamine modulating system (TMMS). This system modulates emotional/motivational activities mediated by the limbic circuitry, where glutamate is the major excitatory neurotransmitter. Two main concepts are the basis of this review. First, since 1950 and the discovery of the antipsychotic activity of the dopamine D2 receptor antagonist chlorpromazine, it appears that drugs that can modulate the TMMS possess therapeutic psychiatric properties. Second, the concept of glutamate/trimonoamine imbalance in the cortico-striato-thalamo-cortical loop that has been so successful in explaining the pathophysiology of Parkinson disease has been applied in the pathophysiology of schizophrenia. This review will focus on the complex interactions between the fast synaptic glutamatergic transmission and the TMMS in specific parts of the limbic lobe and we will try to link these interactions to some psychiatric disorders, mainly depression, schizophrenia and drug addiction.

Positional therapy for obstructive sleep apnea: an objective measurement of patients' usage and efficacy at home.

BACKGROUND: Positional therapy that prevents patients from sleeping supine has been used for many years to manage positional obstructive sleep apnea (OSA). However, patients' usage at home and the long term efficacy of this therapy have never been objectively assessed. METHODS: Sixteen patients with positional OSA who refused or could not tolerate continuous positive airway pressure (CPAP) were enrolled after a test night study (T0) to test the efficacy of the positional therapy device. The patients who had a successful test night were instructed to use the device every night for three months. Nightly usage was monitored by an actigraphic recorder placed inside the positional device. A follow-up night study (T3) was performed after three months of positional therapy. RESULTS: Patients used the device on average 73.7 ± 29.3% (mean ± SD) of the nights for 8.0 ± 2.0 h/night. 10/16 patients used the device more than 80% of the nights. Compared to the baseline (diagnostic) night, mean apnea-hypopnea index (AHI) decreased from 26.7 ± 17.5 to 6.0 ± 3.4 with the positional device (p<0.0001) during T0 night. Oxygen desaturation (3%) index also fell from 18.4 ± 11.1 to 7.1 ± 5.7 (p = 0.001). Time spent supine fell from 42.8 ± 26.2% to 5.8 ± 7.2% (p < 0.0001). At three months (T3), the benefits persisted with no difference in AHI (p = 0.58) or in time spent supine (p = 0.98) compared to T0 night. The Epworth sleepiness scale showed a significant decrease from 9.4 ± 4.5 to 6.6 ± 4.7 (p = 0.02) after three months. CONCLUSIONS: Selected patients with positional OSA can be effectively treated by a positional therapy with an objective compliance of 73.7% of the nights and a persistent efficacy after three months.

Nicotinamide phosphoribosyltransferase as a target in inflammation- related disorders.

NAD(+) biosynthesis through nicotinamide phosphoribosyltransferase (NAMPT) holds potential as a target for the treatment of inflammatory disorders due to NAD(+)'s role in immune cell signaling and metabolism. In addition to its activity as an enzyme, NAMPT is also secreted in the extracellular space where it acts as a pro-inflammatory and proangiogenic cytokine. NAMPT inhibition with FK866 has anti-inflammatory activity in different models of immune disorders and it prevents ischemia-reperfusion-induced heart damage by dampening the production of neutrophil chemoattractants. NAMPT blockade with a neutralizing antibody has beneficial effects in an acute lung injury model. Last, but not least, the anticancer activity of NAMPT inhibitors may also reflect, at least in part, their ability to modify the cancer microenvironment through their anti-inflammatory properties. Overall, NAMPT inhibition holds potential for the treatment of inflammation-related disorders and the development of effective and safe NAMPT inhibitors remains an area of strong interest in pharmaceutical research.