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Background While adult outcome in autism spectrum disorder (ASD) is generally measured using socially valued roles, it could also be understood in terms of aspects related to health status – an approach that could inform on potential gender differences. Methods We investigated gender differences in two aspects of outcome related to health-status, i.e. general functioning and self-perceived health status, and co-occurring health conditions in a large multi-center sample of autistic adults. Three hundred and eighty-three participants were consecutively recruited from the FondaMental Advanced Centers of Expertise for ASD cohort (a French network of seven expert centers) between 2013 and 2020. Evaluation included a medical interview, standardized scales for autism diagnosis, clinical and functional outcomes, self-perceived health status and verbal ability. Psychosocial function was measured using the Global Assessment of Functioning scale. Results While autistic women in this study were more likely than men to have socially valued roles, female gender was associated with poorer physical and mental health (e.g. a 7-fold risk for having three or more co-occurring physical health conditions) and a poorer self-perceived health status. Psychosocial function was negatively associated with depression and impairment in social communication. Half of the sample had multiple co-occurring health conditions but more than 70% reported that their visit at the Expert Center was their first contact with mental health services. Conclusions To improve objective and subjective aspects of health outcome, gender differences and a wide range of co-occurring health conditions should be taken into account when designing healthcare provision for autistic adults.

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".

Purpose This study aims to explore the overlap between symptoms of depression, anxiety, irritability and aggressiveness in autism spectrum disorder (ASD), to measure specific and idiosyncratic emotional responses. Design/methodology/approach A total of 42 high functioning adolescents and adults, between 12 and 39 years old, meeting the diagnostic and statistical manual of mental disorders – 5 criteria for ASD were selected from the InFoR Autism cohort. Data were analyzed in an exploratory way using Hill and Smith and K-medoids cluster analysis. Findings The authors found an aggregation of anxiety, depression, aggressive behaviors and irritability. Cluster analysis was maximized for two groups with 17 and 25 participants, respectively. The first group was characterized by high levels of symptoms of irritability, aggressiveness, hyperactivity and intermediate levels of anxiety and depression. In the first group, participants had significantly higher levels of autistic symptoms considering the social responsiveness scale and repetitive behavior scale-revised scales (relatives’ reports) suggesting that a particular group of subjects with a high level of ASD specific symptoms may express anxiety and depression in a specific way based on externalizing behaviors in addition to the common mood and anxiety symptoms. Research limitations/implications Improved understanding of the aggregation of externalized symptoms with symptoms of anxiety and mood disorders in ASD should lead to a better understanding of the underlying mechanisms related to emotion dysregulation in ASD. Practical implications Improved knowledge of the symptoms could lead to enhanced detection of psychiatric comorbidities in ASD. Originality/value The study was based on a transdiagnostic approach of psychiatric symptoms in individuals with ASD. Aggregation and clustering analysis was used to explore naive patterns of these psychiatric symptoms.

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.

International audience; Repetitive behaviors (RB) represent a wide spectrum of symptoms ranging from sensory-motor stereotypies to complex cognitive rituals, frequently dichotomized as low- and high-order sub-groups of symptoms. Even though these subgroups are considered as phenomenologically distinct in autism spectrum disorder (ASD) and obsessive-compulsive disorder (OCD), brain imaging and genetic studies suggest that they have common mechanisms and pathways. This discrepancy may be explained by the frequent intellectual disability reported in ASD, which blurs the RB expressivity. Given the high heritability of RB, that is, the diversity of symptoms expressed in the relatives are dependent on those expressed in their probands, we hypothesize that if RB expressed in ASD or OCD are two distinct entities, then the RB expressed in relatives will also reflect these two dimensions. We thus conduct a linear discriminant analysis on RB in both the relatives of probands with ASD and OCD and subjects from the general population (n = 1023). The discriminant analysis results in a classification of 81.1% of the controls (p

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.

Attention Deficit and Hyperactive Disorder (ADHD) and Autism Spectrum Disorders (ASD) are frequent comorbid neurodevelopmental conditions and the overlap between both disorders remains to be delineated. A more complete understanding of the shared genetic and environmental factors is needed. Using a family-based method, we evaluated the risk of ADHD in a group of relatives with an ASD proband (ASD-) and a group of relatives with an ASD and ADHD proband (ASD+). We enrolled 1245 individuals in the study: 499 probands, their 746 first-degree relatives and 140 controls. We used a multivariate generalized estimating equation (GEE) model, in which the dependent variable was the ADHD diagnosis in the relatives and the independent variable the ASD+ or ASD- in probands. We adjusted for sociodemographic factors (age, sex, IQ) and for the nature of the familial relationship with the affected proband (parent or sibling). Among the probands, there were 287 ASD- and 212 ASD+ individuals. ADHD was more frequent in relatives (19%) than in the control group (7%) (p = 0.001). The risk of ADHD was higher in the ASD+ relatives group than in the ASD- relatives group (GEE model OR 1.58 [95% CI 1.04-2.38], p = 0.032). This result was found in parents (OR 1.96 [95% CI 1.14-3.36], but not in siblings (OR 1.28 [95% CI 0.84-1.94], p = 0.434). Our study provides a representative estimate of the family distribution of ADHD in relatives of ASD probands but supports the modest effect of shared genetic and environmental factors between both disorders.

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.

Objective The posterior superior temporal sulcus (pSTS) plays a critical role in the ‘social brain’. Its neurodevelopment and relationship with the social impairment in autism spectrum disorders (ASD) are not well understood. We explored the relationship between social cognition and the neurodevelopment of the pSTS in ASD. Method We included 44 adults with high-functioning ASD and 36 controls. We assessed their performances on the ‘Reading the mind in the eyes’ test (for 34 of 44 subjects with ASD and 30 of 36 controls), their fixation time on the eyes with eye tracking (for 35 of 44 subjects with ASD and 30 of 36 controls) and the morphology of the caudal branches of the pSTS (length and depth), markers of the neurodevelopment, with structural MRI. Results The right anterior caudal ramus of the pSTS was significantly longer in patients with ASD compared with controls (52.6 mm vs. 38.3 mm; P = 1.4 × 10−3; Cohen's d = 0.76). Its length negatively correlated with fixation time on the eyes (P = 0.03) in the ASD group and with the ‘Reading the mind in the eyes’ test scores in both groups (P = 0.03). Conclusion Our findings suggest that the neurodevelopment of the pSTS is related to the ASD social impairments.

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.

Rubinstein-Taybi syndrome (RTS) is a rare genetic disease that associates intellectual disability with somatic characteristics. We have conducted a study of the overall motor abilities of RTS participants. Static postural performance as well as gait parameters were somewhat decreased, although not significantly compared to typically developing (TD) participants. In contrast, the motor skills requiring a high level of visuomotor coordination were considerably degraded in RTS participants compared to TD participants. We also found that cognitive status was significantly correlated with performance for tasks requiring a higher level of visuomotor coordination in RTS but not TD participants. Our study demonstrates a reduction in the motor performance of RTS participants and a link between the level of intellectual disability and motor capacities.

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.

Autism spectrum disorders: heterogeneous genetic etiologies. Autism Spectrum Disorders (ASD) are neurodevelopmental diseases affecting around 1% of the general population. Symptoms appear early in the development, usually before 3 years of life. Clinical features are extremely heterogeneous as genetic etiologies that underlie ASD. Genetic findings are present in 25% of ASD patients especially in specific cellular pathways as neurodevelopment or synapse architecture. ASD appears to be the combination of several de novo or/and inherited deleterious genetic variants. Here we propose to discuss genetic findings in these disorders and see how genetic research is able to give new treatment for ASD.Autisme : une maladie génétique hétérogène. L’autisme est la forme la plus sévère des troubles du spectre autistique qui touchent actuellement 1 % de la population générale et dont les symptômes apparaissent au cours des premières années de vie. Ces troubles très hétérogènes au plan clinique sont majoritairement causés par des anomalies génétiques hétérogènes et complexes survenant de novo ou héritées et dont les effets délétères peuvent se cumuler. Ces mutations génétiques touchent principalement des grandes voies cellulaires comme le neurodéveloppement et l’architecture synaptique. Le dépistage précoce, les interventions comportementales intensives, la poursuite des recherches génétiques permettront à l’avenir d’améliorer le pronostic encore sombre des troubles du spectre autistique.

International audience; School inclusion of students with Autism Spectrum Disorder (ASD) is still a research challenge. Promoting school inclusion notably requires the understanding of cognitive underpinnings of ASD related limitations in school adaptive behaviors. More, such knowledge might provide relevant intervention’s targets for fostering school inclusion of youths with ASD. Our study aimed at exploring the relationships between school-related adaptive behaviors and cognitive functioning in youths with ASD according to the distinction of general (IQ, age) and specific cognitive factors (social-emotional skills, executive functions).Forty-five participants were recruited in specialized classrooms, including 27 with ASD (mean age = 14.26), and 18 with intellectual and/or learning disability (non-ASD) (mean age = 14.17). The participants, their parents and/or the specialized teachers answered to a set of tests measuring the cognitive functioning, school-related socio-adaptive behaviors and quality of life. After group comparisons on each measure, we performed multiple regression analyses for determining whether general and/or specific cognitive factors may predict school-related socio-adaptive behaviors and quality of life, which constitute hallmarks of school disability.Both groups exhibited equal performances on socio-emotional and executive measures. By contrast, youths with ASD showed more difficulties in socio-adaptive behaviors than youths in no-ASD group. Regression analyses revealed a single strong contribution of socio-emotional skills for predicting such limitations in the ASD group, while IQ and age were the best contributors in the non-ASD group. The low quality of life reported in both groups was slightly predicted by executive performances. These results emphasized the critical role of socio-emotional skills in the socio-adaptive functioning of youths with ASD at school, as well as the role of executive functioning in school-related quality of life.

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.

OBJECTIVE To quantify the objective level of sleepiness in adult attention-deficit/hyperactivity disorder (ADHD) patients and to determine the relationship between excessive daytime sleepiness and simulated driving performance. METHOD Forty adult ADHD patients (DSM-IV criteria) and 19 matched healthy control subjects were included between June 30, 2010, and June 19, 2013. All participants completed the Epworth Sleepiness Scale and the Manchester Driving Behavior Questionnaire. After nocturnal polysomnography, they performed 2 neuropsychological tests, a 4 × 40-minute Maintenance of Wakefulness Test, and a 1-hour driving session. The primary outcome measure was the mean sleep latency on the Maintenance of Wakefulness Test. ADHD patients were divided into 3 groups defined by their Maintenance of Wakefulness Test scores. Participants (patients and control subjects) were allocated as follows: sleepy ADHD (0-19 min), intermediate ADHD (20-33 min), alert ADHD (34-40 min), and control group (34-40 min). The driving performance outcome was the mean standard deviation of lateral position of the vehicle during the simulated session. RESULTS The group mean (SD) Epworth Sleepiness Scale score was higher in ADHD patients (12.1 [4.4]) than in controls (6.0 [2.7]) (P < .001). On the basis of the Maintenance of Wakefulness Test scores, 14 patients (35%) were in the sleepy group, 20 (50%) were in the intermediate group, and only 6 (15%) were in the alert group. Sleepy ADHD patients exhibited significantly deteriorated driving performance compared to the other 3 groups (P < .01). CONCLUSIONS Our study shows that a significant proportion of adult ADHD patients exhibit an objective excessive daytime sleepiness, which, in addition, has an impact on simulated driving performance. Excessive daytime sleepiness, therefore, may be a key element needed to better evaluate these ADHD patients. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT01160874.

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.

Resume Le trouble deficit de l’attention/hyperactivite (TDA/H) est un trouble frequent chez l’enfant qui persiste souvent a l’âge adulte. Des plaintes de sommeil sont frequemment rapportees dans le TDA/H. Les liens entre sommeil et TDA/H ont fait l’objet de recherche depuis les annees 1990 d’abord chez les enfants et plus recemment chez les adultes presentant un TDA/H. Des donnees se sont accumulees concernant une association entre le TDA/H et le syndrome des jambes sans repos (SJSR), le syndrome d’apnees obstructives du sommeil (SAOS), les hypersomnies et les troubles du rythme circadien. L’objectif de cet article est de faire une revue de ces associations et de leurs consequences afin d’explorer de futures perspectives de prise en charge therapeutique et de recherche scientifique.

The links between sleep and attention-deficit hyperactivity disorder (ADHD) have been a topic of ongoing research and clinical interest in children over the last three decades and more recently in adults suffering from ADHD. Clinically, psychiatrists are faced with frequent reports of sleep disorders in adults and children with ADHD and conversely, sleep specialists report certain symptoms of ADHD (attention deficits, urge for fidgeting) in patients suffering from primary sleep disorders. Excessive sleepiness is found in ADHD and sleep disorders such as hypersomnia, sleep breathing disorder (SDB), periodic limb movements in sleep (PLMS) and circadian rhythm disorders. This has encouraged authors to suggest a model of ADHD involving a deficit in alertness. The aim of this article is to clarify the pathophysiological rationale for the relationship between sleep/arousal and attention-deficit/hyperactivity disorder and to explore future perspectives in terms of management, treatment and development of research fields.

Objectif Les troubles du spectre de l’autisme (TSA) ne sont pas toujours reperes precocement, pouvant amener a un diagnostic tardif, parfois a l’âge adulte. Cela constitue un enjeu majeur de sante publique. Soixante pour cent des patients presentant un TSA n’ont pas de deficience intellectuelle. L’objectif de cette etude est d’evaluer l’âge au diagnostic des adultes atteints d’un TSA sans deficit intellectuel. L’objectif secondaire est de determiner les facteurs qui l’influencent. Methode Il s’agit d’une etude d’observation analytique, par etude de cohorte, multicentrique retrospective, s’etendant sur une periode de 10 ans, de septembre 2008 a mars 2018. Elle a ete realisee au sein des 4 centres experts TSA SDI de la Fondation FondaMental en France metropolitaine. Les criteres d’inclusion etaient : l’âge strictement superieur a 16 ans, la presence d’un TSA selon les criteres du DSM-5, l’absence de deficience intellectuelle, et la consultation dans l’un des 4 centres experts, avec l’evaluation par les outils d’entretien standardises ADOS et ADI-R, et par l’echelle de quotient intellectuel WAIS-IV. Resultats Deux cent quarante patients ont ete inclus, dont 74,38 % de sexe masculin. La moyenne d’âge au diagnostic etait de 20,6 ans ± 13,5 ans. Nous n’avons pas retrouve de differences significatives d’âge au diagnostic entre hommes et femmes. Parmi les differents facteurs etudies, ceux influencant significativement cet âge etaient : l’annee de naissance (avec un âge au diagnostic plus precoce chez les moins de 26 ans compare aux plus de 26 ans), l’intensite precoce des symptomes (mesuree avec l’ADI-R), et le QI (principalement l’indice de comprehension verbale et l’indice de vitesse de traitement). Chez les femmes, le principal facteur influencant l’âge au diagnostic etait le score de communication a l’ADOS. Conclusion L’etude que nous avons realisee constate un âge moyen au diagnostic de 20,6 ans. L’âge au diagnostic est positivement correle au QI. Il n’y a pas de difference statistiquement significative selon le genre dans notre etude. Chez les hommes, l’âge au diagnostic est inversement proportionnel avec la severite des symptomes precoces, et proportionnel au score du quotient intellectuel. L’etude revele un âge au diagnostic plus tardif chez les femmes ayant de meilleures capacites de communication. Les strategies de compensation chez les adultes TSA sans deficit intellectuel seraient interessantes a etudier comme facteur influencant l’âge au diagnostic.

While forensic studies have reported higher than community rates of mental disorders in imprisoned populations, few studies have focused on attention-deficit/hyperactivity disorder (ADHD) in these subjects. The aim of this study was to investigate ADHD prevalence among young French male prisoners. A specific diagnostic interview (Conners' Adult ADHD Diagnostic Interview for DSM-IV, CAADID) was used. Correlations between ADHD, subsyndromal ADHD, and criminal features were investigated. 11% of young male prisoners among 93 male subjects aged 18-35 years met the criteria for actual ADHD, and 17% met those for childhood ADHD. Considering ADHD and subsyndromal ADHD, prevalence was about 43% in adulthood. ADHD and subsyndromal ADHD in adulthood were significantly associated with a higher number of imprisonments and a younger age at first arrest. It could be advisable to better identify subjects with ADHD symptoms among prison populations.

Depressive, anxiety and obsessive symptoms frequently co-occur with anorexia nervosa (AN). The relationship between these clinical manifestations and the biological changes caused by starvation is not well understood. It has been hypothesised that reduced availability of tryptophan (TRP) could reduce serotonin activity and thus trigger these comorbid symptoms. The aim of this study, during re-feeding in individuals with AN, was to analyse covariations across measures of nutritional status, depressive and anxiety symptoms, and peripheral serotonin markers. Depressive and anxiety symptoms, nutritional status and serotonin markers--whole blood serotonin content, plasma TRP and the ratio between TRP and large neutral amino acids--were assessed for 42 AN participants at admission to inpatient treatment and after re-feeding. Biological measures were compared to those obtained in 42 non-eating disordered subjects. For those with AN, psychological, nutritional and biological parameters improved significantly during hospitalisation. Levels of serotonin markers were significantly lower in the AN group compared to the control group, at admission and at discharge. Increase in the TRP/LNAA ratio was correlated with a decrease in depressive symptoms. In addition, there was a positive correlation between serotonin levels and symptoms of both anxiety and depression at discharge. We speculate that enhanced TRP availability during re-feeding, as a result of the increase in the TRP/LNAA ratio, could restore serotonin neurotransmission and lead to a decrease in depressive symptoms. The association between serotonin and anxiety and depressive symptoms would be consistent with numerous observations indicating abnormal functioning of the serotoninergic system in AN.