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Autism spectrum disorder (ASD) is a neurodevelopmental condition which compromises various cognitive and behavioural domains. The understanding of the pathophysiology and molecular neurobiology of ASD is still an open critical research question. Here, we aimed to address ASD neurochemistry in the same time point at key regions that have been associated with its pathophysiology: the insula, hippocampus, putamen and thalamus. We conducted a multivoxel proton magnetic resonance spectroscopy (1H-MRS) study to non-invasively estimate the concentrations of total choline (GPC + PCh, tCho), total N-acetyl-aspartate (NAA + NAAG, tNAA) and Glx (Glu + Gln), presenting the results as ratios to total creatine while investigating replication for ratios to total choline as a secondary analysis. Twenty-two male children aged between 10 and 18 years diagnosed with ASD (none with intellectual disability, in spite of the expected lower IQ) and 22 age- and gender-matched typically developing (TD) controls were included. Aspartate ratios were significantly lower in the insula (tNAA/tCr: p = 0.010; tNAA/tCho: p = 0.012) and putamen (tNAA/tCr: p = 0.015) of ASD individuals in comparison with TD controls. The Glx ratios were significantly higher in the hippocampus of the ASD group (Glx/tCr: p = 0.027; Glx/tCho: p = 0.011). Differences in tNAA and Glx indices suggest that these metabolites might be neurochemical markers of region-specific atypical metabolism in ASD children, with a potential contribution for future advances in clinical monitoring and treatment.
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Transtorno do Espectro Autista , Transtorno Autístico , Criança , Humanos , Masculino , Adolescente , Transtorno Autístico/metabolismo , Glutamina/metabolismo , Transtorno do Espectro Autista/diagnóstico por imagem , Transtorno do Espectro Autista/metabolismo , Ácido Aspártico/metabolismo , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Colina/metabolismo , Receptores de Antígenos de Linfócitos T/metabolismo , Creatina/metabolismo , Ácido Glutâmico/metabolismoRESUMO
INTRODUCTION: Autism is a common neurodevelopmental condition with a complex genetic aetiology that includes contributions from monogenic and polygenic factors. Many autistic people have unmet healthcare needs that could be served by genomics-informed research and clinical trials. The primary aim of the European Autism GEnomics Registry (EAGER) is to establish a registry of participants with a diagnosis of autism or an associated rare genetic condition who have undergone whole-genome sequencing. The registry can facilitate recruitment for future clinical trials and research studies, based on genetic, clinical and phenotypic profiles, as well as participant preferences. The secondary aim of EAGER is to investigate the association between mental and physical health characteristics and participants' genetic profiles. METHODS AND ANALYSIS: EAGER is a European multisite cohort study and registry and is part of the AIMS-2-TRIALS consortium. EAGER was developed with input from the AIMS-2-TRIALS Autism Representatives and representatives from the rare genetic conditions community. 1500 participants with a diagnosis of autism or an associated rare genetic condition will be recruited at 13 sites across 8 countries. Participants will be given a blood or saliva sample for whole-genome sequencing and answer a series of online questionnaires. Participants may also consent to the study to access pre-existing clinical data. Participants will be added to the EAGER registry and data will be shared externally through established AIMS-2-TRIALS mechanisms. ETHICS AND DISSEMINATION: To date, EAGER has received full ethical approval for 11 out of the 13 sites in the UK (REC 23/SC/0022), Germany (S-375/2023), Portugal (CE-085/2023), Spain (HCB/2023/0038, PIC-164-22), Sweden (Dnr 2023-06737-01), Ireland (230907) and Italy (CET_62/2023, CEL-IRCCS OASI/24-01-2024/EM01, EM 2024-13/1032 EAGER). Findings will be disseminated via scientific publications and conferences but also beyond to participants and the wider community (eg, the AIMS-2-TRIALS website, stakeholder meetings, newsletters).
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Transtorno Autístico , Genômica , Sistema de Registros , Sequenciamento Completo do Genoma , Criança , Humanos , Masculino , Transtorno Autístico/genética , Estudos de Coortes , Europa (Continente) , Estudos Multicêntricos como Assunto , Projetos de PesquisaRESUMO
Williams syndrome (WS) is a neurodevelopmental disorder characterized by severe visuospatial deficits, particularly affecting spatial navigation and wayfinding. Creating egocentric (viewer-dependent) and allocentric (viewer-independent) representations of space is essential for the development of these abilities. However, it remains unclear whether egocentric and allocentric representations are impaired in WS. In this study, we investigate egocentric and allocentric frames of reference in this disorder. A WS group (n = 18), as well as a chronological age-matched control group (n = 20), a non-verbal mental age-matched control group (n = 20) and a control group with intellectual disability (n = 17), was tested with a computerized and a 3D spatial judgment task. The results showed that WS participants are impaired when performing both egocentric and allocentric spatial judgments even when compared with mental age-matched control participants. This indicates that a substantial deficit affecting both spatial representations is present in WS. The egocentric impairment is in line with the dorsal visual pathway deficit previously reported in WS. Interestingly, the difficulties found in performing allocentric spatial judgments give important cues to better understand the ventral visual functioning in WS.
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Ego , Julgamento/fisiologia , Percepção Espacial/fisiologia , Síndrome de Williams/fisiopatologia , Síndrome de Williams/psicologia , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Sinais (Psicologia) , Feminino , Humanos , Masculino , Estimulação Luminosa/métodos , Vias Visuais , Adulto JovemRESUMO
This paper introduces a prototype for clinical research documentation using the structured information model HL7 CDA and clinical terminology (SNOMED CT). The proposed solution was integrated with the current electronic health record system (EHR-S) and aimed to implement interoperability and structure information, and to create a collaborative platform between clinical and research teams. The framework also aims to overcome the limitations imposed by classical documentation strategies in real-time healthcare encounters that may require fast access to complex information. The solution was developed in the pediatric hospital (HP) of the University Hospital Center of Coimbra (CHUC), a national reference for neurodevelopmental disorders, particularly for autism spectrum disorder (ASD), which is very demanding in terms of longitudinal and cross-sectional data throughput. The platform uses a three-layer approach to reduce components' dependencies and facilitate maintenance, scalability, and security. The system was validated in a real-life context of the neurodevelopmental and autism unit (UNDA) in the HP and assessed based on the functionalities model of EHR-S (EHR-S FM) regarding their successful implementation and comparison with state-of-the-art alternative platforms. A global approach to the clinical history of neurodevelopmental disorders was worked out, providing transparent healthcare data coding and structuring while preserving information quality. Thus, the platform enabled the development of user-defined structured templates and the creation of structured documents with standardized clinical terminology that can be used in many healthcare contexts. Moreover, storing structured data associated with healthcare encounters supports a longitudinal view of the patient's healthcare data and health status over time, which is critical in routine and pediatric research contexts. Additionally, it enables queries on population statistics that are key to supporting the definition of local and global policies, whose importance was recently emphasized by the COVID pandemic.
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BACKGROUND: The concomitant role of the Central Executive, the Saliency and the Social Cognition networks in autism spectrum disorder (ASD) in demanding ecological tasks remains unanswered. We addressed this question using a novel task-based fMRI virtual-reality task mimicking a challenging daily-life chore that may present some difficulties to individuals with ASD: the EcoSupermarketX. METHODS: Participants included 29 adolescents: 15 with ASD and 15 with typical neurodevelopment (TD). They performed the EcoSupermarketX (a shopping simulation with three goal-oriented sub-tasks including "no cue", "non-social" or "social" cues), during neuroimaging and eye-tracking. RESULTS: ASD differed from TD only in total time and distance to complete the "social cue" sub-task with matched eye-tracking measures. Neuroimaging revealed simultaneous hyperactivation across social, executive, and saliency circuits in ASD. In contrast, ASD showed reduced activation in the parahippocampal gyrus, involved in scene recognition. CONCLUSIONS: When performing a virtual shopping task matching the performance of controls, ASD adolescents hyperactivate three core networks: executive, saliency and social cognition. Parahippocampal hypoactivation is consistent with effortless eidetic scene processing, in line with the notion of peaks and valleys of neural recruitment in individuals with ASD. These hyperactivation/hypoactivation patterns in daily life tasks provide a circuit-level signature of neural diversity in ASD, a possible intervention target.
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Transtorno do Espectro Autista , Adolescente , Transtorno do Espectro Autista/complicações , Cognição , Humanos , Imageamento por Ressonância Magnética , Neuroimagem , Cognição SocialRESUMO
Social attention deficits represent a central impairment of patients suffering from autism spectrum disorder (ASD), but the nature of such deficits remains controversial. We compared visual attention regarding social (faces) vs. non-social stimuli (objects), in an ecological diagnostic context, in 46 children and adolescents divided in two groups: ASD (N = 23) and typical neurodevelopment (TD) (N = 23), matched for chronological age and intellectual performance. Eye-tracking measures of visual scanning, while exploring and describing scenes from three different tasks from the Autism Diagnostic Observation Schedule (ADOS), were analyzed: "Description of a Picture," "Cartoons," and "Telling a Story from a Book." Our analyses revealed a three-way interaction between Group, Task, and Social vs. Object Stimuli. We found a striking main effect of group and a task dependence of attentional allocation: while the TD attended first and longer to faces, ASD participants became similar to TD when they were asked to look at pictures while telling a story. Our results suggest that social attention allocation is task dependent, raising the question whether spontaneous attention deficits can be rescued by guiding goal-directed actions.
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Executive functioning (EF) impairments in Autism Spectrum Disorder (ASD) impact on complex functions, such as social cognition. We assessed this link between EF, attentional cueing, and social cognition with a novel ecological task, "EcoSupermarketX." Our task had three blocks of increasing executive load and incorporated social and non-social cues, with different degrees of saliency. Performance of ASD and typical neurodevelopment was compared. The ASD showed a significant performance dependence on the presence of contextual cues. Difficulties increased as a function of cognitive load. Between-group differences were found both for social and non-social salient cues. Eye-tracking measures showed significantly larger fixation time of more salient social cues in ASD. In sum, EcoSupermarketX is sensitive to detect EF and attentional cueing deficits in ASD.
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LAY ABSTRACT: Neurofeedback is an emerging therapeutic approach in neuropsychiatric disorders. Its potential application in autism spectrum disorder remains to be tested. Here, we demonstrate the feasibility of real-time functional magnetic resonance imaging volitional neurofeedback in targeting social brain regions in autism spectrum disorder. In this clinical trial, autism spectrum disorder patients were enrolled in a program with five training sessions of neurofeedback. Participants were able to control their own brain activity in this social brain region, with positive clinical and neural effects. Larger, controlled, and blinded clinical studies will be required to confirm the benefits.
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Transtorno do Espectro Autista , Transtorno Autístico , Neurorretroalimentação , Transtorno do Espectro Autista/diagnóstico por imagem , Transtorno do Espectro Autista/terapia , Transtorno Autístico/diagnóstico por imagem , Transtorno Autístico/terapia , Encéfalo/diagnóstico por imagem , Humanos , Imageamento por Ressonância MagnéticaRESUMO
Language outcome in individuals with autism spectrum disorder (ASD) is predicted by early developmental milestones and cognitive abilities. The development and acquisition of expressive language (particularly the onset of first phrases) is a relevant clinical milestone by school age, since its early presentation is associated to better long-term life outcomes and to lower core clinical severity of ASD. Focusing on predictors of language in ASD children, a number of outstanding questions remain to be answered, namely, whether there are differences in the early key neurodevelopmental abilities and whether those differences in a specific period of time might predict verbal development and acquisition of expressive language. We aim to understand how the neurodevelopmental profile of ASD children evolves from the preschool to the school age and if and which subarea can better predict acquisition of expressive language. Children with ASD (N = 205) were evaluated with a structured assessment of neurodevelopment in two different age periods: 1) preschool period (mean age four years) and 2) reassessment in the school period (mean age seven years). Our findings demonstrate that in nonverbal preschool children with ASD normal or near normal Performance Developmental Quotient (superior to 73.5) evaluated at preschool age is a good predictor of later language development in ASD, which has important implications for intervention programs targeting this population and family information.
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Transtorno do Espectro Autista/fisiopatologia , Desenvolvimento da Linguagem , Criança , Pré-Escolar , Feminino , Humanos , Estudos Longitudinais , Masculino , PrognósticoRESUMO
Interpersonal distance (IPD) is a simple social regulation metric which is altered in autism. We performed a stop-distance paradigm to evaluate IPD regulation in autism spectrum disorder (ASD) and control groups in a real versus a virtual environment mimicking in detail the real one. We found a bimodal pattern of IPDs only in ASD. Both groups showed high IPD correlations between real and virtual environments, but the significantly larger slope in the control group suggests rescaling, which was absent in ASD. We argue that loss of nuances like non-verbal communication, such as perception of subtle body gestures in the virtual environment, lead to changed regulation of IPD in controls, whilst ASD participants show similar deficits in perceiving such subtle cues in both environments.
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Transtorno do Espectro Autista/psicologia , Realidade Virtual , Transtorno Autístico , Sinais (Psicologia) , Feminino , Gestos , Humanos , Masculino , Comunicação não VerbalRESUMO
The nature of neurochemical changes in autism spectrum disorder (ASD) remains controversial. We compared medial prefrontal cortex (mPFC) neurochemistry of twenty high-functioning children and adolescents with ASD without associated comorbidities and fourteen controls. We observed reduced total N-acetylaspartate (tNAA) and total creatine, increased Glx/tNAA but unchanged glutamate + glutamine (Glx) and unchanged absolute or relative gamma-aminobutyric acid (GABA+) in the ASD group. Importantly, both smaller absolute and relative GABA+ levels were associated with worse communication skills and developmental delay scores assessed by the autism diagnostic interview-revised (ADI-R). We conclude that tNAA is reduced in the mPFC in ASD and that glutamatergic metabolism may be altered due to unbalanced Glx/tNAA. Moreover, GABA+ is related to autistic symptoms assessed by the ADI-R.
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Ácido Aspártico/análogos & derivados , Transtorno do Espectro Autista/metabolismo , Ácido Glutâmico/metabolismo , Glutamina/metabolismo , Córtex Pré-Frontal/metabolismo , Ácido gama-Aminobutírico/metabolismo , Adolescente , Ácido Aspártico/metabolismo , Transtorno do Espectro Autista/diagnóstico por imagem , Biomarcadores/metabolismo , Criança , Feminino , Humanos , Espectroscopia de Ressonância Magnética/métodos , Masculino , Córtex Pré-Frontal/química , Córtex Pré-Frontal/diagnóstico por imagemRESUMO
OBJECTIVE: Electroencephalographic biomarkers have been widely investigated in autism, in the search for diagnostic, prognostic and therapeutic outcome measures. Here we took advantage of the information available in temporal oscillatory patterns evoked by simple perceptual decisions to investigate whether stimulus dependent oscillatory signatures can be used as potential biomarkers in autism spectrum disorder (ASD). METHODS: We studied an extensive set of stimuli (9 categories of faces) and performed data driven classification (Support vector machine, SVM) of ASD vs. Controls with features based on the EEG power responses. We carried out an extensive time-frequency and synchrony analysis of distinct face categories requiring different processing mechanisms in terms of non-holistic vs. holistic processing. RESULTS: We found that the neuronal oscillatory responses of low gamma frequency band, locked to photographic and abstract two-tone (Mooney) face stimulus presentation are decreased in ASD vs. the control group. We also found decreased time-frequency (TF) responses in the beta band in ASD after 350â¯ms, possibly related to motor preparation. On the other hand, synchrony in the 30-45â¯Hz band showed a distinct spatial pattern in ASD. These power changes enabled accurate classification of ASD with an SVM approach. SVM accuracy was approximately 85%. ROC curves showed about 94% AUC (area under the curve). Combination of Mooney and Photographic face stimuli evoked features enabled a better separation between groups, reaching an AUC of 98.6%. CONCLUSION: We identified a relative decrease in EEG responses to face stimuli in ASD in the beta (15-30â¯Hz; >350â¯ms) and gamma (30-45â¯Hz; 55-80â¯Hz; 50-350â¯ms) frequency ranges. These can be used as input of a machine learning approach to separate between groups with high accuracy. SIGNIFICANCE: Future studies can use EEG time-frequency patterns evoked by particular types of faces as a diagnostic biomarker and potentially as outcome measures in therapeutic trials.
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Transtorno do Espectro Autista/diagnóstico , Encéfalo/fisiopatologia , Tomada de Decisões/fisiologia , Percepção Visual/fisiologia , Adolescente , Adulto , Transtorno do Espectro Autista/fisiopatologia , Eletroencefalografia , Humanos , Masculino , Estimulação Luminosa , Reprodutibilidade dos Testes , Máquina de Vetores de Suporte , Adulto JovemRESUMO
Imagery of facial expressions in Autism Spectrum Disorder (ASD) is likely impaired but has been very difficult to capture at a neurophysiological level. We developed an approach that allowed to directly link observation of emotional expressions and imagery in ASD, and to derive biomarkers that are able to classify abnormal imagery in ASD. To provide a handle between perception and action imagery cycles it is important to use visual stimuli exploring the dynamical nature of emotion representation. We conducted a case-control study providing a link between both visualization and mental imagery of dynamic facial expressions and investigated source responses to pure face-expression contrasts. We were able to replicate the same highly group discriminative neural signatures during action observation (dynamical face expressions) and imagery, in the precuneus. Larger activation in regions involved in imagery for the ASD group suggests that this effect is compensatory. We conducted a machine learning procedure to automatically identify these group differences, based on the EEG activity during mental imagery of facial expressions. We compared two classifiers and achieved an accuracy of 81% using 15 features (both linear and non-linear) of the signal from theta, high-beta and gamma bands extracted from right-parietal locations (matching the precuneus region), further confirming the findings regarding standard statistical analysis. This robust classification of signals resulting from imagery of dynamical expressions in ASD is surprising because it far and significantly exceeds the good classification already achieved with observation of neutral face expressions (74%). This novel neural correlate of emotional imagery in autism could potentially serve as a clinical interventional target for studies designed to improve facial expression recognition, or at least as an intervention biomarker.
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Deficits in the interpretation of others' intentions from gaze-direction or other social attention cues are well-recognized in ASD. Here we investigated whether an EEG brain computer interface (BCI) can be used to train social cognition skills in ASD patients. We performed a single-arm feasibility clinical trial and enrolled 15 participants (mean age 22y 2m) with high-functioning ASD (mean full-scale IQ 103). Participants were submitted to a BCI training paradigm using a virtual reality interface over seven sessions spread over 4 months. The first four sessions occurred weekly, and the remainder monthly. In each session, the subject was asked to identify objects of interest based on the gaze direction of an avatar. Attentional responses were extracted from the EEG P300 component. A final follow-up assessment was performed 6-months after the last session. To analyze responses to joint attention cues participants were assessed pre and post intervention and in the follow-up, using an ecologic "Joint-attention task." We used eye-tracking to identify the number of social attention items that a patient could accurately identify from an avatar's action cues (e.g., looking, pointing at). As secondary outcome measures we used the Autism Treatment Evaluation Checklist (ATEC) and the Vineland Adaptive Behavior Scale (VABS). Neuropsychological measures related to mood and depression were also assessed. In sum, we observed a decrease in total ATEC and rated autism symptoms (Sociability; Sensory/Cognitive Awareness; Health/Physical/Behavior); an evident improvement in Adapted Behavior Composite and in the DLS subarea from VABS; a decrease in Depression (from POMS) and in mood disturbance/depression (BDI). BCI online performance and tolerance were stable along the intervention. Average P300 amplitude and alpha power were also preserved across sessions. We have demonstrated the feasibility of BCI in this kind of intervention in ASD. Participants engage successfully and consistently in the task. Although the primary outcome (rate of automatic responses to joint attention cues) did not show changes, most secondary neuropsychological outcome measures showed improvement, yielding promise for a future efficacy trial. (clinical-trial ID: NCT02445625-clinicaltrials.gov).
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BACKGROUND: We present a novel virtual-reality P300-based Brain Computer Interface (BCI) paradigm using social cues to direct the focus of attention. We combined interactive immersive virtual-reality (VR) technology with the properties of P300 signals in a training tool which can be used in social attention disorders such as autism spectrum disorder (ASD). NEW METHOD: We tested the novel social attention training paradigm (P300-based BCI paradigm for rehabilitation of joint-attention skills) in 13 healthy participants, in 3 EEG systems. The more suitable setup was tested online with 4 ASD subjects. Statistical accuracy was assessed based on the detection of P300, using spatial filtering and a Naïve-Bayes classifier. RESULTS: We compared: 1 - g.Mobilab+ (active dry-electrodes, wireless transmission); 2 - g.Nautilus (active electrodes, wireless transmission); 3 - V-Amp with actiCAP Xpress dry-electrodes. Significant statistical classification was achieved in all systems. g.Nautilus proved to be the best performing system in terms of accuracy in the detection of P300, preparation time, speed and reported comfort. Proof of concept tests in ASD participants proved that this setup is feasible for training joint attention skills in ASD. COMPARISON WITH EXISTING METHODS: This work provides a unique combination of 'easy-to-use' BCI systems with new technologies such as VR to train joint-attention skills in autism. CONCLUSIONS: Our P300 BCI paradigm is feasible for future Phase I/II clinical trials to train joint-attention skills, with successful classification within few trials, online in ASD participants. The g.Nautilus system is the best performing one to use with the developed BCI setup.
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Transtorno do Deficit de Atenção com Hiperatividade/etiologia , Transtorno Autístico/complicações , Interfaces Cérebro-Computador , Encéfalo/fisiopatologia , Comportamento Social , Adulto , Transtorno do Deficit de Atenção com Hiperatividade/classificação , Sinais (Psicologia) , Eletroencefalografia , Potenciais Evocados P300/fisiologia , Estudos de Viabilidade , Feminino , Humanos , Masculino , Interface Usuário-Computador , Adulto JovemRESUMO
OBJECTIVE: The PARK2 gene encodes Parkin, a component of a multiprotein E3 ubiquitin ligase complex that targets substrate proteins for proteasomal degradation. PARK2 mutations are frequently associated with Parkinson's disease, but structural alterations have also been described in patients with neurodevelopmental disorders (NDD), suggesting a pathological effect ubiquitous to neurodevelopmental and neurodegenerative brain processes. The present study aimed to define the critical regions for NDD within PARK2. MATERIALS AND METHODS: To clarify PARK2 involvement in NDDs, we examined the frequency and location of copy number variants (CNVs) identified in patients from our sample and reported in the literature and relevant databases, and compared with control populations. RESULTS: Overall, the frequency of PARK2 CNVs was higher in controls than in NDD cases. However, closer inspection of the CNV location in PARK2 showed that the frequency of CNVs targeting the Parkin C-terminal, corresponding to the ring-between-ring (RBR) domain responsible for Parkin activity, is significantly higher in NDD cases than in controls. In contrast, CNVs targeting the N-terminal of Parkin, including domains that regulate ubiquitination activity, are very common both in cases and in controls. CONCLUSION: Although PARK2 may be a pathological factor for NDDs, likely not all variants are pathogenic, and a conclusive assessment of PARK2 variant pathogenicity requires an accurate analysis of their location within the coding region and encoded functional domains.
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Transtorno do Espectro Autista/genética , Ubiquitina-Proteína Ligases/genética , Transtorno do Espectro Autista/metabolismo , Simulação por Computador , Variações do Número de Cópias de DNA , Feminino , Humanos , Masculino , Mutação , Transtornos do Neurodesenvolvimento/genética , Transtornos do Neurodesenvolvimento/metabolismo , Doença de Parkinson/genética , Doença de Parkinson/metabolismo , Portugal , Relação Estrutura-Atividade , Ubiquitina-Proteína Ligases/metabolismoRESUMO
Individuals with autism spectrum disorder (ASD) are impaired in face recognition and emotional expression identification. According to current models, there are at least three levels of face processing: first order (two eyes, above a nose, which is above a mouth), second order (the relative distance between features), and holistic (ability to recognize as faces images that lack distinctive facial features). Some studies have reported deficits in configural and holistic processing in individuals with ASD. We investigated the neural correlates of these phenomena by measuring event-related potentials in high-functioning adults with ASD and healthy controls, during a face decision task, using a comprehensive set of photographic, schematic and Mooney upright and inverted faces, and scrambled images. Behaviorally, ASD and healthy controls were performance matched. At the electrophysiological level, individuals with ASD showed a bilateral N170 inversion effect in latency and left lateralized in amplitude for photographic faces, with bilaterally longer latencies and left higher amplitudes (more negative) N170 for inverted than upright photographic faces, and a right lateralized N170 inversion effect in latency for schematic faces. We conclude that under performance-matched conditions, adults with ASD show preserved N170 inversion effects and associated sparing of facial configural processing. An oral presentation of this work can be consulted using the following link, Supplemental digital content 1, http://links.lww.com/WNR/A382.
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Transtorno do Espectro Autista/fisiopatologia , Potenciais Evocados/fisiologia , Reconhecimento Facial/fisiologia , Adulto , Eletroencefalografia , Humanos , Masculino , Adulto JovemRESUMO
The influence of specific autism spectrum disorder (ASD) deficits in Intelligence Quotients (IQ), Indexes and subtests from the Wechsler Intelligence Scale for Children-III was investigated in 445 school-aged children: ASD (N = 224) and other neurodevelopmental disorders (N = 221), matched by Full-Scale IQ and chronological age. ASD have lower scores in the VIQ than PIQ. The core distinctive scores between groups are Processing Speed Index and "Comprehension" and "Coding" subtests with lower results in ASD. ASD group with normal/high IQ showed highest score on "Similarities" subtest whereas the lower IQ group performed better on "Object Assembly". The results replicated our previous work on adaptive behaviour, showing that adaptive functioning is positively correlated with intellectual profile, especially with the Communication domain in ASD.
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Transtorno do Espectro Autista/psicologia , Inteligência , Transtornos do Neurodesenvolvimento/psicologia , Adaptação Psicológica , Adolescente , Criança , Feminino , Humanos , Testes de Inteligência , MasculinoRESUMO
We investigated the influence of specific autism spectrum disorder (ASD) deficits in learning adaptive behaviour, besides intelligence quotient (IQ). Participated 217 school-aged: ASD (N = 115), and other neurodevelopmental disorders (OND) groups (N = 102) matched by Full-Scale IQ. We compared standard scores of Vineland Adaptive Behaviour Scale (VABS) in communication, daily living skills, socialization and adaptive behaviour composite. Pearson-correlation analysis was performed between each domain of VABS and Full-Scale, Verbal and Performance IQ, and chronological age (CA). Results indicated that impairment in adaptive behaviour within the domain of socialization skills remains a distinctive factor of ASD versus OND, independently of intellectual disability (ID). Co-occurring ID result in further debilitating effects on overall functioning, especially in ASD. CA is negatively associated with VABS scores.
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Atividades Cotidianas/psicologia , Adaptação Psicológica , Transtorno Autístico/diagnóstico , Transtorno Autístico/psicologia , Deficiências do Desenvolvimento/diagnóstico , Deficiências do Desenvolvimento/psicologia , Adaptação Psicológica/fisiologia , Adolescente , Adulto , Criança , Feminino , Humanos , Inteligência/fisiologia , Testes de Inteligência/normas , Masculino , SocializaçãoRESUMO
BACKGROUND: Validating the potential pathogenicity of copy number variants (CNVs) identified in genome-wide studies of autism spectrum disorders (ASD) requires detailed assessment of case/control frequencies, inheritance patterns, clinical correlations, and functional impact. Here, we characterize a small recurrent duplication in the annexin A1 (ANXA1) gene, identified by the Autism Genome Project (AGP) study. METHODS: From the AGP CNV genomic screen in 2,147 ASD individuals, we selected for characterization an ANXA1 gene duplication that was absent in 4,964 population-based controls. We further screened the duplication in a follow-up sample including 1,496 patients and 410 controls, and evaluated clinical correlations and family segregation. Sequencing of exonic/downstream ANXA1 regions was performed in 490 ASD patients for identification of additional variants. RESULTS: The ANXA1 duplication, overlapping the last four exons and 3'UTR region, had an overall prevalence of 11/3,643 (0.30%) in unrelated ASD patients but was not identified in 5,374 controls. Duplication carriers presented no distinctive clinical phenotype. Family analysis showed neuropsychiatric deficits and ASD traits in multiple relatives carrying the duplication, suggestive of a complex genetic inheritance. Sequencing of exonic regions and the 3'UTR identified 11 novel changes, but no obvious variants with clinical significance. CONCLUSIONS: We provide multilevel evidence for a role of ANXA1 in ASD etiology. Given its important role as mediator of glucocorticoid function in a wide variety of brain processes, including neuroprotection, apoptosis, and control of the neuroendocrine system, the results add ANXA1 to the growing list of rare candidate genetic etiological factors for ASD.