Diagnosis of sleep apnoea using a mandibular monitor and machine learning analysis: one-night agreement compared to in-home polysomnography

Background: The capacity to diagnose obstructive sleep apnoea (OSA) must be expanded to meet an estimated disease burden of nearly one billion people worldwide. Validated alternatives to the gold standard polysomnography (PSG) will improve access to testing and treatment. This study aimed to evaluate the diagnosis of OSA, using measurements of mandibular movement (MM) combined with automated machine learning analysis, compared to in-home PSG. Methods: 40 suspected OSA patients underwent single overnight in-home sleep testing with PSG (Nox A1, ResMed, Australia) and simultaneous MM monitoring (Sunrise, Sunrise SA, Belgium). PSG recordings were manually analysed by two expert sleep centres (Grenoble and London); MM analysis was automated. The Obstructive Respiratory Disturbance Index calculated from the MM monitoring (MM-ORDI) was compared to the PSG (PSG-ORDI) using intraclass correlation coefficient and Bland-Altman analysis. Receiver operating characteristic curves (ROC) were constructed to optimise the diagnostic performance of the MM monitor at different PSG-ORDI thresholds (5, 15, and 30 events/hour). Results: 31 patients were included in the analysis (58% men; mean (SD) age: 48 (15) years; BMI: 30.4 (7.6) kg/m2). Good agreement was observed between MM-ORDI and PSG-ORDI (median bias 0.00; 95% CI −23.25 to + 9.73 events/hour). However, for 15 patients with no or mild OSA, MM monitoring overestimated disease severity (PSG-ORDI 5–15: MM-ORDI overestimation + 3.70 (95% CI −0.53 to + 18.32) events/hour). In 16 patients with moderate-severe OSA (n = 9 with PSG-ORDI 15–30 events/h and n = 7 with a PSG-ORD > 30 events/h), there was an underestimation (PSG-ORDI > 15: MM-ORDI underestimation −8.70 (95% CI −28.46 to + 4.01) events/hour). ROC optimal cut-off values for PSG-ORDI thresholds of 5, 15, 30 events/hour were: 9.53, 12.65 and 24.81 events/hour, respectively. These cut-off values yielded a sensitivity of 88, 100 and 79%, and a specificity of 100, 75, 96%. The positive predictive values were: 100, 80, 95% and the negative predictive values 89, 100, 82%, respectively. Conclusion: The diagnosis of OSA, using MM with machine learning analysis, is comparable to manually scored in-home PSG. Therefore, this novel monitor could be a convenient diagnostic tool that can easily be used in the patients’ own home. Clinical Trial Registration: https://clinicaltrials.gov, identifier NCT0426255

The effects of amisulpride on five dimensions of psychopathology in patients with schizophrenia: a prospective open- label study

BACKGROUND: The efficacy of antipsychotics can be evaluated using the dimensional models of schizophrenic symptoms. The D(2)/D(3)-selective antagonist amisulpride has shown similar efficacy and tolerability to other atypical antipsychotics. The aim of the present study was to determine the efficacy of amisulpride on the dimensional model of schizophrenic symptoms and tolerability in latin schizophrenic patients. METHOD: Eighty schizophrenic patients were enrolled and 70 completed a prospective open-label 3-month study with amisulpride. The schizophrenic symptoms, psychosocial functioning and side-effects were evaluated with standardized scales. RESULTS: The patients showed significant improvement in the five dimensions evaluated. Amisulpride (median final dose 357.1 mg/d) was well-tolerated without treatment-emergent extrapyramidal side-effects. CONCLUSION: Amisulpride showed efficacy on different psychopathological dimensions and was well tolerated, leading to consider this drug a first line choice for the treatment of schizophrenia

Oppositional COMT Val158Met effects on resting state functional connectivity in adolescents and adults

© 2014, The Author(s).Prefrontal dopamine levels are relatively increased in adolescence compared to adulthood. Genetic variation of COMT (COMT Val158Met) results in lower enzymatic activity and higher dopamine availability in Met carriers. Given the dramatic changes of synaptic dopamine during adolescence, it has been suggested that effects of COMT Val158Met genotypes might have oppositional effects in adolescents and adults. The present study aims to identify such oppositional COMT Val158Met effects in adolescents and adults in prefrontal brain networks at rest. Resting state functional connectivity data were collected from cross-sectional and multicenter study sites involving 106 healthy young adults (mean age 24 ± 2.6 years), gender matched to 106 randomly chosen 14-year-olds. We selected the anterior medial prefrontal cortex (amPFC) as seed due to its important role as nexus of the executive control and default mode network. We observed a significant age-dependent reversal of COMT Val158Met effects on resting state functional connectivity between amPFC and ventrolateral as well as dorsolateral prefrontal cortex, and parahippocampal gyrus. Val homozygous adults exhibited increased and adolescents decreased connectivity compared to Met homozygotes for all reported regions. Network analyses underscored the importance of the parahippocampal gyrus as mediator of observed effects. Results of this study demonstrate that adolescent and adult resting state networks are dose-dependently and diametrically affected by COMT genotypes following a hypothetical model of dopamine function that follows an inverted U-shaped curve. This study might provide cues for the understanding of disease onset or dopaminergic treatment mechanisms in major neuropsychiatric disorders such as schizophrenia and attention deficit hyperactivity disorder

New evidence of factor structure and measurement invariance of the SDQ across five European nations

The main purpose of the present study was to test the internal structure and to study the measurement invariance of the Strength and Difficulties Questionnaire (SDQ), self-reported version, in five European countries. The sample consisted of 3012 adolescents aged between 12 and 17 years (M = 14.20; SD = 0.83). The five-factor model (with correlated errors added), and the five-factor model (with correlated errors added) with the reverse-worded items allowed to cross-load on the Prosocial subscale, displayed adequate goodness of-fit indices. Multi-group confirmatory factor analysis showed that the five-factor model had partial strong measurement invariance by countries. A total of 11 of the 25 items were non-invariant across samples. The level of internal consistency of the Total difficulties scores was .84, ranging between .69 and .78 for the SDQ subscales. The findings indicate that the SDQ's scales need to be modified in various ways for screening emotional and behavioural problems in the five European countries that were analyzed

Human subcortical brain asymmetries in 15,847 people worldwide reveal effects of age and sex

The two hemispheres of the human brain differ functionally and structurally. Despite over a century of research, the extent to which brain asymmetry is influenced by sex, handedness, age, and genetic factors is still controversial. Here we present the largest ever analysis of subcortical brain asymmetries, in a harmonized multi-site study using meta-analysis methods. Volumetric asymmetry of seven subcortical structures was assessed in 15,847 MRI scans from 52 datasets worldwide. There were sex differences in the asymmetry of the globus pallidus and putamen. Heritability estimates, derived from 1170 subjects belonging to 71 extended pedigrees, revealed that additive genetic factors influenced the asymmetry of these two structures and that of the hippocampus and thalamus. Handedness had no detectable effect on subcortical asymmetries, even in this unprecedented sample size, but the asymmetry of the putamen varied with age. Genetic drivers of asymmetry in the hippocampus, thalamus and basal ganglia may affect variability in human cognition, including susceptibility to psychiatric disorders

Mourning and melancholia revisited: correspondences between principles of Freudian metapsychology and empirical findings in neuropsychiatry

Freud began his career as a neurologist studying the anatomy and physiology of the nervous system, but it was his later work in psychology that would secure his place in history. This paper draws attention to consistencies between physiological processes identified by modern clinical research and psychological processes described by Freud, with a special emphasis on his famous paper on depression entitled 'Mourning and melancholia'. Inspired by neuroimaging findings in depression and deep brain stimulation for treatment resistant depression, some preliminary physiological correlates are proposed for a number of key psychoanalytic processes. Specifically, activation of the subgenual cingulate is discussed in relation to repression and the default mode network is discussed in relation to the ego. If these correlates are found to be reliable, this may have implications for the manner in which psychoanalysis is viewed by the wider psychological and psychiatric communities

«La relation de limitation et d’exception dans le français d’aujourd’hui : excepté, sauf et hormis comme pivots d’une relation algébrique »

L’analyse des emplois prépositionnels et des emplois conjonctifs d’ “excepté”, de “sauf” et d’ “hormis” permet d’envisager les trois prépositions/conjonctions comme le pivot d’un binôme, comme la plaque tournante d’une structure bipolaire. Placées au milieu du binôme, ces prépositions sont forcées par leur sémantisme originaire dûment métaphorisé de jouer le rôle de marqueurs d’inconséquence systématique entre l’élément se trouvant à leur gauche et celui qui se trouve à leur droite. L’opposition qui surgit entre les deux éléments n’est donc pas une incompatibilité naturelle, intrinsèque, mais extrinsèque, induite. Dans la plupart des cas (emplois limitatifs), cette opposition prend la forme d’un rapport entre une « classe » et le « membre (soustrait) de la classe », ou bien entre un « tout » et une « partie » ; dans d’autres (emplois exceptifs), cette opposition se manifeste au contraire comme une attaque de front portée par un « tout » à un autre « tout ». De plus, l’inconséquence induite mise en place par la préposition/conjonction paraît, en principe, tout à fait insurmontable. Dans l’assertion « les écureuils vivent partout, sauf en Australie » (que l’on peut expliciter par « Les écureuils vivent partout, sauf [qu’ils ne vivent pas] en Australie »), la préposition semble en effet capable d’impliquer le prédicat principal avec signe inverti, et de bâtir sur une telle implication une sorte de sous énoncé qui, à la rigueur, est totalement inconséquent avec celui qui le précède (si « les écureuils ne vivent pas en Australie », le fait qu’ils « vivent partout » est faux). Néanmoins, l’analyse montre qu’alors que certaines de ces oppositions peuvent enfin être dépassées, d’autres ne le peuvent pas. C’est, respectivement, le cas des relations limitatives et des relations exceptives. La relation limitative, impliquant le rapport « tout » - « partie », permet de résoudre le conflit dans les termes d’une somme algébrique entre deux sous énoncés pourvus de différent poids informatif et de signe contraire. Les valeurs numériques des termes de la somme étant déséquilibrées, le résultat est toujours autre que zéro. La relation exceptive, au contraire, qui n’implique pas le rapport « tout » - « partie », n’est pas capable de résoudre le conflit entre deux sous énoncés pourvus du même poids informatif et en même temps de signe contraire : les valeurs numériques des termes de la somme étant symétriques et égales, le résultat sera toujours équivalent à zéro

Increased white matter connectivity in euthymic bipolar patients: diffusion tensor tractography between the subgenual cingulate and the amygdalo-hippocampal complex.

Bipolar disorder has been associated with anatomical as well as functional abnormalities in a brain network that mediates normal and impaired emotion regulation. Previous brain imaging studies have highlighted the subgenual cingulate (SC) and the amygdalo-hippocampal (AH) complex as core regions of this network. Thus we investigated white matter (WM) fiber tracts between the SC and the AH region, the uncinate fasciculus, as well as between two control regions (pons and cerebellum), using diffusion tensor imaging tractography in 16 euthymic bipolar patients (BP) and 16 sex-, age- and handedness-matched controls. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) of the reconstructed fiber bundle and the number of virtual reconstructed fibers were compared between groups. The tractography results revealed a significantly increased number of reconstructed fibers between the left SC and left AH in BP as compared to healthy controls. FA and ADC of the reconstructed fiber tract did not differ significantly between the groups. Furthermore, no significant group differences were observed neither for reconstructed fiber tracts between the right SC and right AH nor between the control regions. The present results suggest an altered WM pathway between the left SC and AH region and thus extend previous findings of anatomical and functional modifications in these structures in BP

Brain morphometry and cognitive performance in detoxified alcohol-dependents with preserved psychosocial functioning.

The extent of structural brain damage and related cognitive deficits has been little described in alcohol-dependent individuals with preserved social functioning. Thus, we investigated the relationship between regional alterations, executive performance, and drinking history. Volumes of gray and white matter were assessed using magnetic resonance imaging voxel-based morphometry in healthy men and in detoxified alcohol-dependent men with good psychosocial functioning. Their executive performance was assessed using neuropsychological tests. Regression analyses were carried out in the regions in which volume differences were detected. Decreases in gray matter were detected bilaterally in alcohol-dependents in the dorsolateral frontal cortex (up to 20% lower), and to a lesser extent in the temporal cortex, insula, thalamus, and cerebellum. Decreases in white matter volume were widespread, being up to 10% in corpus callosum. The degradation of neuropsychological performance correlated with gray matter volume decreases in the frontal lobe, insula, hippocampus, thalami and cerebellum, and with white matter decrease in the brainstem. An early age at first drinking was associated with decreased gray matter volumes in the cerebellum, brainstem (pons), and frontal regions. Regional alteration in gray and white matter volume was associated with impairment of executive function despite preserved social and somatic functioning in detoxified patients. Besides involving frontal regions, these findings are consistent with a cerebello-thalamo-cortical model of impaired executive functions in alcohol-dependent individuals