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Background. Repetitive and restricted behaviors and interests (RRBI) are core symptoms of autism with a complex entity and are commonly categorized into ‘motor-driven’ and ‘cognitively-driven’. RRBI symptomatology depends on the individual’s clinical environment limiting the understanding of RRBI physiology, particularly their associated neuroanatomical structures. The complex RRBI heterogeneity needs to explore the whole RRBI spectrum by integrating the clinical context (autistic individuals, their relatives and typical developing (TD) individuals). We hypothesized that different RRBI dimensions would emerge by exploring the whole spectrum of RRBI, and that these dimensions are associated with neuroanatomical signatures - involving cortical & subcortical areas. Method. A sample of 792 individuals composed of 267 autistic subjects, their 370 first-degree relatives and 155 TD individuals was enrolled in the study. We assessed the whole patterns of RRBI in each individual by using the Repetitive Behavior Scale-Revised and the Yale-Brown Obsessive Compulsive Scale. We estimated brain volumes using MRI scanner for a subsample of the subjects (n=152, 42 ASD, 89 relatives and 13 TD). We first investigated the dimensionality of RRBI by performing a principal component analysis on all items of these scales and included all the sampling population. We then explored the relationship between RRBI-derived factors with brain volumes using linear regression models. Results. We identified 3 main factors (with 30.3% of the RRBI cumulative variance): Factor 1 (FA1, 12.7%) reflected mainly the ‘motor-driven’ RRBI symptoms; Factor 2 and 3 (respectively 8.8% and 7.9%) gathered mainly Y-BOCS related items and represented the ‘cognitively-driven’ RRBI symptoms. These three factors were significantly associated with the right/left putamen volumes but with opposite effects: FA1 was negatively associated with an increased volume of the right/left putamen conversely to FA2 & FA3 (all uncorrected pConclusion. Our results suggested 3 coherent RRBI dimensions involving the putamen commonly and other structures according to the RRBI dimension. The exploration of the putamen’s integrative role in RSBI needs to be strengthened in further studies.

Background Autism spectrum disorders (ASD) are neurodevelopmental disorders characterised by deficits in social communication or interaction and repetitive behaviours. Maternal immune activation (MIA) during the mid-pregnancy is a known risk factor for ASD. Although reported in 15% of affected individuals, little is known about the specificity of their clinical profiles. Adaptive skills represent a holistic approach to a person's competencies and reflect specifically in autism, their strengths and difficulties. Methods In this study, we hypothesised that individual with ASD with a history of MIA (MIA+) could be more severely socio-adaptively impaired than those without MIA during pregnancy (MIA−). To answer this question, we considered two independent cohorts of individuals with ASD (PARIS study and FACE ASD) screened for pregnancy history, and used a supervised and unsupervised statistical approach. Results We included 295 mother-child dyads with 14% of them with MIA+. We found that ASD-MIA+ individuals displayed more severe maladaptive behaviors, specifically in their socialization abilities. MIA+ directly influenced individual's socio-adaptive skills, independent of other covariates, including ASD severity. Interestingly, MIA+ may affected persistently the socio-adaptive behavioral trajectories of individuals with ASD. Limitations : The current study has a retrospective design with possible recall bias regarding the MIA event and, even if pooled from two cohorts, has a relatively small population. In addition, we were limited by the number of covariables available potentially impacted socio-adaptive behaviors. Larger prospective study with additional dimensions related to ASD is needed to confirm our results Conclusions Specific pathophysiological pathways may explain these clinical peculiarities of ASD- MIA+ individuals, and may open the way to new perspectives in deciphering the phenotypic complexity of autism and for the development of specific immunomodulatory strategies.

International audience; In recent years, many psycho-educational technologies were studied to address the school-related difficulties encountered by students with autism spectrum disorder (ASD). However, most of them remain individual-centered and do not consider the social environment. To fill this gap, this study reports on the user-centered design of a web-based support tool, which aims to support communication and coordination between parents, school staff, and health professionals of middle and high school students with ASD, in the context of elaborating, implementing, and following an Individualized Education Plan (IEP). The study followed a two-step design process: 1) a need analysis for identifying information domains deemed important by the stakeholders; 2) through a participative iterative design process, a panel of professionals and parents provided ideas and feedback on the design, which was integrated into subsequent prototype versions of the "ToGather" app.; Ces dernières années, de nombreuses technologies psycho-éducatives ont été étudiées pour répondre aux difficultés scolaires rencontrées par les élèves avec trouble du spectre autistique (TSA). Cependant, la plupart d'entre elles restent centrées sur l'individu et ne prennent pas en compte l'environnement social. Pour combler cette lacune, cette étude porte sur la conception centrée-utilisateur d'un outil en ligne, qui vise à soutenir la communication et la coordination entre les parents, le personnel scolaire et les professionnels médico-sociaux des élèves de collège et de lycée atteints de TSA, dans le contexte de l'élaboration, de la mise en œuvre et du suivi d'un projet personnalisé de scolarisation (PPS). L'étude a suivi un processus de conception en deux étapes : 1) une analyse des besoins pour identifier les domaines d'information jugés importants par les parties prenantes ; 2) par le biais d'un processus de conception participatif et itératif, un panel de professionnels et de parents a fourni des idées et des commentaires sur la conception, qui ont été intégrés dans les versions prototypes ultérieures de l'application "ToGather".

Autism spectrum disorders (ASD) are heterogeneous and complex neurodevelopmental conditions that urgently need reliable and sensitive measures to inform diagnosis properly. The Reading the Mind in the Eyes Task (or Eyes Test from now on) is widely used for this purpose. A recent study showed that subcategories of items of the children version of the Eyes Test could be especially discriminative to distinguish ASD and control children. Here, we analyzed the performance on the Eyes Test of 30 high functioning (IQ > 70) adults with ASD and 29 controls from the InFoR cohort multicentric study, using a Generalized Linear Mixed Model. We found that valence and difficulty modulate the performance on the Eyes Test, with easy and positive items being the most discriminative to distinguish ASD and controls. In particular, we suggest this result might be actionable to discriminate ASD patients from controls in subgroups where their overall scores show less difference with controls. We propose for future research the computation of two additional indexes when using the Eyes Test: the first focusing on the easy and positive items (applying a threshold of 70% of correct responses for these items, above which people are at very low risk of having ASD) and the second focusing on the performance gain from difficult to easy items (with a progression of less than 15% showing high risk of having ASD). Our findings open the possibility for a major change in how the Eyes Test is used to inform diagnosis in ASD. LAY SUMMARY: The Eyes Test is used worldwide to inform autism spectrum disorders (ASD) diagnosis. We show here that ASD and neurotypical adults show the most difference in performance on subgroups of items: ASD adults do not improve as expected when comparing easy and difficult items, and they do not show an improvement for items displaying a positive feeling. We advise clinicians to focus on these comparisons to increase the property of the test to distinguish people with ASD from neurotypical adults.

Background. Sensory processing atypicalities are part of the core symptoms of autism spectrum disorder (ASD) and could result from an excitation/inhibition imbalance. Yet, the convergence level of phenotypic sensory processing atypicalities with genetic alterations in GABA-ergic and glutamatergic pathways remains poorly understood. This study aimed to characterize the distribution of hypo/hyper-sensory profile among individuals with ASD and investigate the role of deleterious mutations in GABAergic and glutamatergic pathways related genes in sensory processing atypicalities. Method. From the Short Sensory Profile (SSP) questionnaire, we defined and explored a score – the differential Short Sensory Profile (dSSP) - as a normalized and centralized hypo/hypersensitivity ratio for 1136 participants (533 with ASD, 210 first-degree relatives, and 267 controls) from two independent study samples (PARIS and LEAP). We also performed an unsupervised item-based clustering analysis on SSP items scores to validate this new categorization in terms of hypo and hyper sensitivity. We then explored the link between the dSSP score and the burden of deleterious mutations in a subset of individuals for which whole-genome sequencing data were available. Results. We observed a mean dSSP score difference between ASD and controls, driven mostly by a high dSSP score variability among groups (PARIS: p2 = 0.0001, LEAP: p2 = 0.02; LEAP: p=0.01, η2 = 0.01). Clusters were similarly characterized by hypo- and hyper-sensitivity items in both study samples (Cramer's V from 0.64 to 0.69, pLimitations. The major limitation was the dSSP score difficulty to discriminate subjects with a similar quantum of hypo- and hyper- sensory symptoms to those with no such symptoms, resulting both in a similar ratio score of 0.Conclusion. The dSSP score could be a relevant clinical score of the hypo/hyper-sensory individual profile in subjects with ASD. Combined with additional sensory domain characteristics, genetics and endophenotypic substrates, the dSSP score will offer new avenues to explore the underlying neurobiological mechanisms of sensory processing atypicalities in ASD.

Background Inhibitory control and attention processing atypicalities are implicated in various diseases, including autism spectrum disorders (ASD). These cognitive functions can be tested by using visually guided saccade-based paradigms in children, adolescents and adults to determine the time course of such disorders. Methods In this study, using Gap, Step, Overlap and Antisaccade tasks, we analyzed the oculomotor behavior of 82 children, teenagers and adults with high functioning ASD and their peer typically developing (TD) controls in a two-year follow-up study under the auspices of the InFoR-Autism project. Analysis of correlations between oculomotors task measurements and diagnostic assessment of attentional (ADHD-RS and ADHD comorbidity indices) and executive functioning (BRIEF scales) were conducted in order to evaluate their relationship with the oculomotor performance of participants with ASD. Results As indicated by the presence of a Gap and Overlap effects in all age groups, the oculomotor performances of ASD participants showed a preserved capability in overt attention switching. In contrast, the difference in performances of ASD participants in the Antisaccade task, compared to their TD peers, indicated an atypical development of inhibition and executive functions. From correlation analysis between our oculomotor data and ADHD comorbidity index, and scores of attention and executive function difficulties, our findings support the hypothesis that a specific dysfunction of inhibition skills occurs in ASD participants that is independent of the presence of ADHD comorbidity. Limitations These include the relatively small sample size of the ASD group over the study’s two-year period, the absence of an ADHD-only control group and the evaluation of a TD control group solely at the study’s inception. Conclusions Children and teenagers with ASD have greater difficulty in attention switching and inhibiting prepotent stimuli. Adults with ASD can overcome these difficulties, but, similar to teenagers and children with ASD, they make more erroneous and anticipatory saccades and display a greater trial-to-trial variability in all oculomotor tasks compared to their peers. Our results are indicative of a developmental delay in the maturation of executive and attentional functioning in ASD and of a specific impairment in inhibitory control.

ObjectivesDifferent studies centered on social relationship issues among ADHD children struggled to provide a unicist explanation between primary social cognition process alteration on the one hand and a mere symptomatic outcome of the disorder triad on the other. Some authors support the idea of a potential “social phenotype” shared at a different intensity by Attention Deficit/Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD). The point of the study is to characterize this possible social disability in a French ADHD population and compare it to control subjects and subjects with Autism Spectrum Disorder (ASD).MethodsThree groups, composed of 319 subjects aged 6 to 12 years, were recruited in Bordeaux: 88 untreated ADHD subjects, 24 ASD subjects and 207 control subjects. The main measure was the social skill disruption through the rating of the Social Responsiveness Scale (SRS). The ADHD-RS-IV, WFIRS-P and CBCL scales were also used.ResultsAsignificant alteration in social abilities in ADHD children in comparison with controls was noted, with an average raw total SRS score intermediary between the control group and the ASD group (respectively 65.31 ± 20.99, 37.15 ± 16.37 and 95 75 ± 30.83, P < 0.05). When the 5 sub-scores of the SRS were taken into account, if the ASD subjects showed the highest average scores, the alteration pattern appeared qualitatively similar between the ADHD and TSA groups, with also an intermediate dispersion for the ADHD group between the control group and the group with ASD. Finally, more severe impairment of social skills in children with ADHD was associated with increased severity of the disorder (on ADHD-RS-IV scale cotation), higher daily functional impact (WFIRS-P scale), and more frequent behavioral issues (according to CBCL).ConclusionsOur results suggest the presence of social disturbances in ADHD and characterize a symptomatic profile qualitatively similar to that of ASD, but of less intensity. Overall results promote a need for a systematic dimensional assessment of social disability in ADHD.; ObjectifsL’objectif de notre étude est de caractériser les habiletés sociales dans le Trouble Déficit de l’Attention/Hyperactivité (TDAH) en population française et de les comparer à des sujets témoins et à des sujets avec un Trouble du Spectre de l’Autisme (TSA).MéthodesTrois groupes, réunissant 319 sujets âgés de 6 ans à 12 ans, ont été recrutés à Bordeaux : 88 sujets TDAH non-traités par psychostimulant, 24 sujets TSA et 207 sujets témoins. La mesure des habiletés sociales a été faite par la cotation de l’échelle Social Responsiveness Scale (SRS).RésultatsNos résultats objectivent une altération significative des habiletés sociales dans le groupe TDAH par rapport aux témoins. Le score total moyen à la SRS est intermédiaire entre le groupe témoin et le groupe TSA (respectivement 65,31 ± 20,99 ; 37,15 ± 16,37 et 95,75 ± 30, 83 ; p < 0,05). Lorsque sont pris en compte les 5 sous-scores de la SRS, le profil d’altération apparaît similaire qualitativement entre les groupes TDAH et TSA. Enfin, une altération plus sévère des habiletés sociales des enfants avec TDAH s’associe à une sévérité majorée du trouble (ADHD-RS), un retentissement fonctionnel supérieur (WFIRS-P) et des difficultés comportementales plus fréquentes (CBCL).ConclusionsNos résultats apportent des arguments supplémentaires à la présence de perturbations sociales dans le TDA/H et permettent de caractériser un profil symptomatique qualitativement similaire à celui du TSA, mais de moindre intensité. Ces résultats sont en faveur d’une évaluation dimensionnelle systématique de l’altération des habiletés sociales dans le TDAH.

International audience; Irritability and emotional lability have been shown to be severity and impairment factors in community and clinical sample studies and are frequent comorbid features of Attention Deficit Hyperactivity Disorder (ADHD). However, while irritability and emotional lability seem to be closely linked, the differential effect of these two features has received little attention. This study assessed the distinct associations of irritability and emotional lability on symptomatology in children with ADHD. One hundred and eight children diagnosed with ADHD participated in the study. Children were rated by parents on ADHD and comorbid symptomatology with the Conners Rating Scale – Revised. Irritability was the most significant predictive factor of the severity of anxiety and oppositional symptoms. Regarding emotional lability, it was significantly predictive of the severity of hyperactivity symptoms. While emotional lability shares common theoretical characteristics with irritability, each seems to be associated with specific areas. Irritability is a symptom of Oppositional Defiant Disorder, a frequent ADHD comorbidity, and also seems to be related to internalizing disorder (e.g. anxiety). Emotional lability seems to be related to ADHD severity symptoms per se. Both could be clinically informative in the diagnosis of ADHD and its comorbidities.

Objective: Virtual environments have been used to assess children with ADHD but have never been tested as therapeutic tools. We tested a new virtual classroom cognitive remediation program to improve symptoms in children with ADHD. Method: In this randomized clinical trial, 51 children with ADHD (7-11 years) were assigned to a virtual cognitive remediation group, a methylphenidate group, or a psychotherapy group. All children were evaluated before and after therapy with an ADHD Rating Scale, a Continuous Performance Test (CPT), and a virtual classroom task. Results: After therapy by virtual remediation, children exhibited significantly higher numbers of correct hits on the virtual classroom and CPT. These improvements were equivalent to those observed with methylphenidate treatment. Conclusion: Our study demonstrates for the first time that a cognitive remediation program delivered in a virtual classroom reduces distractibility in children with ADHD and could replace methylphenidate treatment in specific cases.

The cerebellum is implicated in social cognition and is likely to be involved in the pathophysiology of autism spectrum disorder (ASD). The goal of our study was to explore cerebellar morphology in adults with ASD and its relationship to eye contact, as measured by fixation time allocated on the eye region using an eye-tracking device. Two-hundred ninety-four subjects with ASD and controls were included in our study and underwent a structural magnetic resonance imaging scan. Global segmentation and cortical parcellation of the cerebellum were performed. A sub-sample of 59 subjects underwent an eye tracking protocol in order to measure the fixation time allocated to the eye region. We did not observe any difference in global cerebellar volumes between ASD patients and controls; however, regional analyses found a decrease of the volume of the right anterior cerebellum in subjects with ASD compared to controls. There were significant correlations between fixation time on eyes and the volumes of the vermis and Crus I. Our results suggest that cerebellar morphology may be related to eye avoidance and reduced social attention. Eye tracking may be a promising neuro-anatomically based stratifying biomarker of ASD.

International audience; Background: Irritability is frequently comorbid with ADHD. Although irritability alone has been linked to deleterious mental health and adaptive issues, the joint developmental course of ADHD and irritability symptoms during childhood as well as its association with later mental health and suicidal outcomes is not fully understood. We aimed to describe the developmental trajectories of childhood ADHD and irritability symptoms and to quantify their association with adolescent mental health and suicidal outcomes.Methods: The Quebec Longitudinal Study of Child Development (QLSCD) included 1407 participants from the general population followed up from age 5 months to 17 years. We used a multitrajectory approach to identify developmental trajectories of childhood (6-12 years) ADHD and irritability symptoms. Outcome measures were adolescent (13-17 years) mental health (psychiatric symptoms/functional impairment) and suicidal outcomes.Results: We identified distinct developmental profiles: combined absent or very low ADHD and absent or very low irritability (940 [66.8%]; reference group), moderately high irritability and low ADHD (158 [11.2%]), moderately high ADHD and low irritability (198 [14.1%]), and combined high ADHD and high irritability (111 [7.9%]). Multivariate modeling showed that, compared to children in the reference group, those in the combined high ADHD and high irritability profile showed higher levels of ADHD continuity (d ranges = 0.40-0.50), externalizing (d ranges = 0.25-0.59), internalizing (d ranges = 0.20-0.29), and functional impairments (d ranges = 0.17-0.48) and suicidal behaviors (odds ratio (OR) = 2.12, confidence interval (CI) = 1.47-3.06) in adolescence.Conclusions: The presence of persistently high levels of irritability along with ADHD symptoms during childhood significantly predicts adolescent ADHD continuity, externalizing, internalizing, and suicidal outcomes. Systematic consideration of irritability when assessing and treating ADHD may improve long-term mental health outcomes.

Background Autism spectrum disorders (ASD) are characterized by abnormal neurodevelopment, genetic, and environmental risk factors, as well as immune dysfunctions. Several lines of evidence suggest alterations in innate immune responses in children with ASD. To address this question in adults with high-functioning ASD (hf-ASD), we sought to investigate the role of natural killer (NK) cells in the persistence of ASD. Methods NK cells from 35 adults with hf-ASD were compared to that of 35 healthy controls (HC), selected for the absence of any immune dysfunctions, at different time-points, and over a 2-year follow-up period for four patients. The phenotype and polyfunctional capacities of NK cells were explored according to infectious stigma and clinical parameters (IQ, social, and communication scores). Results As compared to HC, NK cells from patients with hf-ASD showed a high level of cell activation (p

Objectives. – This study sought to assess facial emotion recognition deficit in children with Attention Deficit/Hyperactivity Disorder (ADHD) and to test the hypothesis that it is increased by comorbid features. Method. – Forty children diagnosed with ADHD were compared with 40 typically developing children,all aged from 7 to 11 years old, on a computerized facial emotion recognition task (based on the Pictures of Facial Affect). Data from parents’ ratings of ADHD and comorbid symptoms (on the Conners’ Revised Parent Rating Scale) were also collected. Results. – Children with ADHD had significantly fewer correct answer scores than typically developing controls on the emotional task while they performed similarly on the control task. Recognition of sadness was especially impaired in children with ADHD. While ADHD symptoms were slightly related to facial emotion recognition deficit, oppositional symptoms were related to a decrease in the number of correct answers on sadness and surprise recognition. Conclusion. – Facial emotion recognition deficit in children with ADHD might be related to an impaired emotional process during childhood. Moreover, Oppositional Defiant Disorder seems to be a risk factorfor difficulties in emotion recognition especially in children with ADHD., Objectif. – Cette étude a pour premier but d’évaluer les capacités de reconnaissance des émotions faciales chez des enfants atteints de trouble déficit de l’attention hyperactivité en les comparant à celles d’enfants au développement typique. Dans un second temps, l’objectif est de tester l’hypothèse qu’un déficit dans la reconnaissance des émotions faciales peut être exacerbé par la sévérité des symptômes comorbides externalisés (l’oppositionalité), internalisés (l’anxiété) et émotionnels (la labilité émotionnelle). Méthode. – Quarante enfants de 7 à 11 ans diagnostiqués avec un trouble déficit de l’attention hyperactivité ont pris part à cette étude ainsi que 40 enfants du même âge non atteints de ce trouble. Pour évaluer la reconnaissance des émotions faciales, un test sur ordinateur a été construit à partir des images contenues dans les Pictures of Facial Affect. Ce test a été construit en trois parties : une phase d’entraînement, une phase de test (reconnaissance des émotions faciales) et une phase contrôle (reconnaissance de formes géométriques). Des données concernant la symptomatologie du trouble déficit de l’attention hyperactivité, externalisée, internalisée et émotionnelle ainsi que la sévérité de celles-ci ont été recueillies par des questionnaires remplis par les parents (Conners’ Revised Parent Rating Scale).

Despite the high clinical burden, little is known about pathophysiology underlying autism spectrum disorder (ASD). Recent resting-state functional magnetic resonance imaging (rs-fMRI) studies have found atypical synchronization of brain activity in ASD. However, no consensus has been reached on the nature and clinical relevance of these alterations. Here, we addressed these questions in four large ASD cohorts. Using rs-fMRI, we identified functional connectivity alterations associated with ASD. We tested for associations of these imaging phenotypes with clinical and demographic factors such as age, sex, medication status, and clinical symptom severity. Our results showed reproducible patterns of ASD-associated functional hyper- and hypoconnectivity. Hypoconnectivity was primarily restricted to sensory-motor regions, whereas hyperconnectivity hubs were predominately located in prefrontal and parietal cortices. Shifts in cortico-cortical between-network connectivity from outside to within the identified regions were shown to be a key driver of these abnormalities. This reproducible pathophysiological phenotype was partially associated with core ASD symptoms related to communication and daily living skills and was not affected by age, sex, or medication status. Although the large effect sizes in standardized cohorts are encouraging with respect to potential application as a treatment and for patient stratification, the moderate link to clinical symptoms and the large overlap with healthy controls currently limit the usability of identified alterations as diagnostic or efficacy readout.

Despite the high clinical burden little is known about pathophysiology underlying autism spectrum disorder (ASD). Recent resting state functional magnetic resonance imaging (rs-fMRI) studies have found atypical synchronization of brain activity in ASD. However, no consensus has been reached on the nature and clinical relevance of these alterations. Here we address these questions in the most comprehensive, large-scale effort to date comprising evaluation of four large ASD cohorts. We followed a strict exploration and replication procedure to identify core rs-fMRI functional connectivity (degree centrality) alterations associated with ASD as compared to typically developing (TD) controls (ASD: N=841, TD: N=984). We then tested for associations of these imaging phenotypes with clinical and demographic factors such as age, sex, medication status and clinical symptom severity. We find reproducible patterns of ASD-associated functional hyper- and hypo-connectivity with hypo-connectivity being primarily restricted to sensory-motor regions and hyper-connectivity hubs being predominately located in prefrontal and parietal cortices. We establish shifts in between-network connectivity from outside to within the identified regions as a key driver of these abnormalities. The magnitude of these alterations is linked to core ASD symptoms related to communication and social interaction and is not affected by age, sex or medication status. The identified brain functional alterations provide a reproducible pathophysiological phenotype underlying the diagnosis of ASD reconciling previous divergent findings. The large effect sizes in standardized cohorts and the link to clinical symptoms emphasize the importance of the identified imaging alterations as potential treatment and stratification biomarkers for ASD.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by dysfunctions in social interactions resulting from a complex interplay between immunogenetic and environmental risk factors. Autoimmunity has been proposed as a major etiological component of ASD. Whether specific autoantibodies directed against brain targets are involved in ASD remains an open question. Here, we identified within a cohort an ASD patient with multiple circulating autoantibodies, including the well-characterized one against glutamate NMDA receptor (NMDAR-Ab). The patient exhibited alexithymia and previously suffered from two major depressive episodes without psychotic symptoms. Using a single molecule-based imaging approach, we demonstrate that neither NMDAR-Ab type G immunoglobulin purified from the ASD patient serum, nor that from a seropositive healthy subject, disorganize membrane NMDAR complexes at synapses. These findings suggest that the autistic patient NMDAR-Abs do not play a direct role in the etiology of ASD and that other autoantibodies directed against neuronal targets should be investigated.El trastorno del espectro autista (TEA) es un trastorno del neurodesarrollo caracterizado por dísfunciones en las interacciones sociales que se traducen en un complejo interjuego entre factores de riesgo ambientales e inmunogenéticos. Se ha propuesto a la autoinmunidad como un componente etiológico importante en el TEA. Sigue pendiente saber si hay autoanticuerpos específicos dirigidos contra blancos cerebrales involucrados en el TEA. En este artículo se identificó, dentro de una cohorte, un paciente con TEA con múltiples autoanticuerpos circulantes, incluyendo uno bien caracterizado contra el receptor de glutamato NMDA (NMDAR-Ab). El paciente presentaba alexitimia y previamente había tenido dos episodios depresivos mayores sin síntomas psicóticos. Mediante técnica de imágenes de molécula única se demostró que ni la γ inmunoglobulina purificada del NMDAR-Ab del suero del paciente con TEA, ni la de un sujeto sano seropositivo desorganizaban los complejos de membrana del NMDAR en las sinapsis. Estos hallazgos sugieren que los auto-anticuerpos del NMDAR de pacientes autistas no juegan un papel directo en la etiología del TEA y que se deben investigar otros autoanticuerpos dirigidos contra blancos neuronales.Les troubles du spectre autistique (TSA) sont des maladies neurodéveloppementales caracterisées par des dysfonctions des interactions sociales provoquées par un jeu complexe entre des facteurs de risque immunogénétiques et environnementaux. L'auto-immunité a été proposée comme composant étiologique majeur des TSA. Il reste à savoir si des auto-anticorps spécifiques dirigés contre des cibles cérébrales sont impliqués dans les TSA. Dans cet article, nous identifions au sein d'une cohorte, un patient TSA ayant de nombreux auto-anticorps circulants dont celui très connu contre le récepteur NMDA du glutamate (NMDAR-Ab). Ce patient présente une alexithymie et a eu antérieurement deux épisodes dépressifs caractérisés sans symptômes psychotiques. Grâce à l'utilisation d'une technique d'imagerie de molécule unique, nous démontrons que ni l'immunoglobuline γ purifiée NMDAR-Ab sérique du patient TSA ni celle d'un patient sain ayant le même anticorps ne désorganisent les complexes membranaires NMDAR au niveau synaptique. Ces résultats semblent indiquer que les auto-anticorps NMDAR-Ab de patients autistes ne jouent pas de rôle direct dans I'étiologie des TSA et que d'autres autoanticorps dirigés contre des cibles neuronales devraient faire l'objet de recherches.

IntroductionThis study describes and compares the behavior of hyperactive and control children playing video games.Subjects and methodsThe sample consisted of 29 ADHD children and 21 controls aged between 6 and 16 years playing video games. We used the Child Behavior Checklist and the Problem Videogame Playing scale (PVP scale). This instrument gives objective measures of problem use, which can be considered as an indication of addictive videogame playing. We designed a questionnaire for the parents, eliciting qualitative information about their child's videogame playing. There were no significant differences concerning frequency or duration of play between ADHD children and controls but differences were observed on the PVP scale. None of the controls scored above four whereas 10 hyperactive children answered affirmatively to five or more questions. These children presented a greater intensity of the disorder than the other ADHD children.ConclusionWhile no differences concerning video game use were found, ADHD children exhibited more problems associated with videogame playing. It seems that a subgroup of ADHD children could be vulnerable to developing dependence upon video games.

The rat forced swimming test (FST) predicts the efficacy of antidepressants, which decrease immobility duration in the test, and can distinguish selective serotonin (5-HT) and noradrenaline (NA) reuptake inhibitors, which, respectively, increase swimming and climbing behaviors. However, dual 5-HT and NA reuptake-inhibition produces climbing behavior solely, thereby suggesting with other data that the NA-system mediates inhibiting interactions on 5-HT-induced swimming in the FST. Since alpha(2)-adrenoreceptors and 5-HT(1A)-receptors have important regulatory functions and are involved in 5-HT/NA interactions, we examined whether the alpha(2)-receptor-antagonist idazoxan and the 5-HT(1A)-receptor-agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) would modify the behavioral pattern induced in the FST by either selective or non-selective antidepressant treatments. The rats were treated subacutely (3 injections IP over 48 h) with: (a) idazoxan (0.5-10 mg/kg) alone, and in combination with desipramine (10 mg/kg), or desipramine + fluoxetine (10/10 mg/kg), or the dual serotonin/noradrenaline reuptake-inhibitor milnacipran (20 mg/kg). (b) 8-OH-DPAT (0.25-1 mg/kg) alone, and in combination with either desipramine (10 mg/kg) or fluoxetine (10 mg/kg). The results indicated: (a) Idazoxan (0.5, 5, 10 mg/kg) produced no anti-immobility effects per se in the FST, antagonized the effects of the NA-reuptake-inhibitor desipramine, and allowed desipramine + fluoxetine, as well as milnacipran, to increase swimming behavior. (b) 8-OH-DPAT produced non-significant effects per se, potentiated desipramine-induced antidepressant-like effects on immobility and climbing, and both antagonized swimming and produced climbing behavior in combination with fluoxetine. Our data support clinical trials suggesting that alpha(2)-receptor-antagonists and 5-HT(1A)-receptor-agonists may be of interest in augmentation strategies for antidepressant treatments. The scoring of active behaviors in the FST appears to be an interesting tool for studying 5-HT/NA interactions induced by antidepressants, as well as for the testing of augmentation strategies.

Many hypotheses have been made to explain the high rate of benzodiazepine consumption in France, including a general cultural and/or familial tendency to use certain types of psychotropic drugs. This study explored the association between lifetime medication use by parents and their children. Two hundred and twenty-one young patients (158 boys and 63 girls) consulting at a child and adolescent psychiatry department, six to 16 years of age (mean = 9.7 years), were screened for lifetime use of psychotropic drugs using a structured interview. Parents were asked about their own consumption, as well as their children’s. Lifetime consumption rates (at least once) were 22.2% in boys and 20.6% in girls, and 19.6% in children less than 11 years old. Higher rates were found in patients with emotional disorders (anxiety disorders and depression). In parents, 45.1% of mothers and 24.1% of fathers reported using medications at least once. A significant association was found between child and parental medication use: 34.1% of children had positive lifetime consumption when their mothers also used medications at least once versus only 13.6% in other children (odds ratio = 3.31 [1.68–6.50]; P = 0.001). The most significant association was found between medication use by girls and their mothers (odds ratio = 12.1 [2.38–61.5];P = 0.003). These data point to the existence of a family pattern of psychotropic drug consumption, especially in females.

BackgroundAttention-deficit hyperactivity disorder (ADHD) has been associated with socioeconomic difficulties later in life. Little research in this area has been based on longitudinal and community studies.AimsTo examine the relationship between childhood attention problems and socioeconomic status 18 years later.MethodUsing a French community sample of 1103 youths followed from 1991 to 2009, we tested associations between childhood attention problems and socioeconomic status between ages 22 and 35 years, adjusting for potential childhood and family confounders.ResultsIndividuals with high levels of childhood attention problems were three times more likely to experience subsequent socioeconomic disadvantage than those with low levels of attention problems (odds ratio 3.44, 95% CI 1.72–6.92). This association remained statistically significant even after adjusting for childhood externalising problems, low family income, parental divorce and parental alcohol problems.ConclusionsThis longitudinal community-based study shows an association between childhood attention problems and socioeconomic disadvantage in adulthood. Taking into account ADHD and associated difficulties could help reduce the long-term socioeconomic burden of the disorder.

International audience; Sexual health-risk behaviors in disruptive children are poorly understood. In a longitudinal population-based sample, event-time analyses showed that subjects with high levels of conduct disorder symptoms, particularly in combination with simultaneously high levels of hyperactivity-inattention symptoms, exhibited the highest risk for earlier sexual activity compared to controls, suggesting the need for prevention.

Contexte scientifique et objectifLes troubles attentionnels ne font pas partie des critères diagnostiques actuels de l’autisme. Pourtant, son intégration au sein du trouble du spectre autistique (TSA) ou sa considération en tant qu’élément comorbide est encore à ce jour débattue. Cette étude a pour objectif l’observation des fonctions attentionnelles d’enfants avec un TSA au moyen de trois situations d’évaluation différentes : test papier crayon, informatique et pour la première fois à notre connaissance un outil de réalité virtuelle.Matériels et méthodesÉvaluation des performances attentionnelles et de l’inhibition de 17 enfants avec un TSA sans retard mental comparés à une population contrôle de 17 enfants appariés en âge et sexe, au travers d’une épreuve écrite d’attention soutenue (R. Zazzo & al., 1969), de trois épreuves informatisées évaluant l’inhibition, la distractibilité et l’attention soutenue (KITAP, P. Zimmermann & al., 2002) ainsi qu’une épreuve de type CPT évaluant l’attention soutenue grâce à un paradigme go/no go mis en présence de distracteurs au sein d’un environnement de classe virtuelle (A. Rizzo & al., 2006).RésultatsAu travers des trois situations d’évaluation, les enfants avec un TSA font plus d’erreurs et d’omissions que les enfants contrôles (p < 0,05). Leurs capacités d’inhibition tendent à être altérées mais de manière non significative dans l’évaluation informatisée (p = 0,1). Nous retrouvons des corrélations positives significatives entre chaque évaluation fonctionnelle réalisée (p < 0,05) hormis entre l’épreuve écrite et de réalité virtuelle (p = 0,09).Conclusions et perspectivesCes résultats sont en faveur de l’hypothèse d’un profil attentionnel commun au sein du TSA incluant altération de l’attention soutenue et distractibilité. Concernant l’inhibition, nos résultats s’avèrent moins concluant, en accord avec les données actuelles de la littérature. Les corrélations positives retrouvées entre nos trois situations d’évaluations suggèrent l’existence de bénéfices potentiels que pourraient apporter les outils de réalité virtuelle dans l’évaluation fonctionnelle des enfants présentant un TSA.

Attention-deficit/hyperactivity disorder is an etiologically heterogeneous neurodevelopmental condition with long-term negative outcomes. However, the early developmental course of hyperactivity-impulsivity and inattention symptoms and their association with previous environmental risk factors are still poorly understoodTo describe the developmental trajectories of hyperactivity-impulsivity and inattention symptoms and to identify their prenatal, perinatal, and postnatal risk factors.Birth cohort from the general population.Quebec Longitudinal Study of Child Development.The sample consisted of 2057 individuals, followed up from age 5 months to 8 years.Prenatal, perinatal, and postnatal risk factors assessed at age 5 months were considered predictors of group membership in high hyperactivity-impulsivity and inattention trajectories from age 17 months to 8 years.The frequency of hyperactivity-impulsivity symptoms tended to slightly decrease with age, whereas the frequency of inattention symptoms substantially increased up to age 6 years. However, trajectories of hyperactivity-impulsivity and inattention symptoms were significantly associated with each other. Risk factors for high trajectories of both types of symptoms were premature birth (adjusted odds ratio [aOR], 1.93; 95% CI, 1.07-3.50), low birth weight (2.11; 1.12-3.98), prenatal tobacco exposure (1.41; 1.03-1.93), nonintact family (1.85; 1.26-2.70), young maternal age at birth of the target child (1.78; 1.17-2.69), paternal history of antisocial behavior (1.78; 1.28-2.47), and maternal depression (1.35; 1.18-1.54).A large range of early risk factors, including prenatal, perinatal social, and parental psychopathology variables, act independently to heighten the likelihood of having persistently high levels of hyperactivity-impulsivity and inattention symptoms from infancy to middle childhood. Early interventions should be experimented with to provide effective tools for attention-deficit/hyperactivity disorder prevention.

Body language plays a major role in social communication. The overall aim of this thesis is to enlighten the contribution of the body in action in social interaction (SI) understanding. A developmental approach reveals the mechanisms responsible for the set-up of social abilities in children, who by nature are extensively social. In autism, a complex developmental disorder, on the contrary the social dimension is deeply affected. Our studies tackle the use of information carried by the body in action, in a social context in this pathology. The originality of our experimental paradigm relies on the use of human motion (HM), or point-light animations, that enable to isolate the social information carried by the body in action only. Subjects watched two actors engaged or not in a social interaction. A two-fold approach, behavioral and using fMRI, reveals the use and the set-up of motor simulation and questions its implication in autism. Children from 4- to 6-years of age and children with autism make use of visual information extracted from HM to understand SI, even though their performance does not reach those of adults. In adults, beyond the mentalizing network, we enlighten the importance of the mirror-neuron system for social cognition. In children, fMRI revealed the early functional recruitment of the inferior frontal gyrus, which is part of the mirror-neuron system, during the observation of social scenes. The general discussion establishes a tight link between the set-up of the mirroring system and the building of action representations. We also question the integrity of this process in autism. In conclusion, these studies bring to light the fundamental role of the mirroring mechanism in the social development of a child., Le langage du corps tient une place prépondérante dans la communication sociale et ceci dès la petite enfance. L'objectif de ce travail de thèse est de déterminer la contribution du corps en action dans la compréhension des interactions sociales (IS). L'approche développementale nous renseigne sur les mécanismes présidant à sa mise en place chez l'enfant, être éminemment social. En revanche dans l'autisme, trouble neurodéveloppemental complexe, la dimension sociale est altérée. Nos études questionnent dans cette pathologie l'utilisation de l'information portée par le corps en mouvement, dans un contexte social. L'originalité de notre paradigme expérimental repose sur l'utilisation de mouvements humains (MH), ou animations en points lumineux, qui permettent d'isoler l'information sociale portée par le corps en action. Nous avons présenté à nos sujets des scènes visuelles présentant deux acteurs engagés dans une interaction sociale ou pas. Une double approche, comportementale et en IRMf, nous éclaire sur l'utilisation et la mise en place de la simulation motrice et nous permet de questionner son implication dans l'autisme. Nous montrons que les enfants entre 4 et 6 ans et les enfants autistes utilisent les informations visuelles portées par le MH pour comprendre une IS, bien que leurs performances ne soient pas encore optimales. Chez l'adulte, en plus du réseau de la mentalisation attendu, nous avons mis en évidence l'importance du réseau des mécanismes miroirs dans la cognition sociale. Chez l'enfant, l'IRMf nous a permis de rapporter pour la première fois un recrutement fonctionnel précoce du gyrus frontal inférieur, siège du système des neurones miroirs, lors de l'observation des scènes sociales. La discussion générale établit un lien étroit entre la mise en place du mécanisme miroir et la construction des représentations de l'action, elle interroge aussi l'intégrité de ce processus dans l'autisme. En conclusion, ces études ouvrent la voie au rôle fondateur du mécanisme miroir dans le développement social de l'enfant.