Synchrony is a multi-faceted construct, defined here as the mutual warmth and responsiveness between a mother and her child. As children with Autism Spectrum Disorders (ASD) struggle to navigate various aspects of social life, we expected that impairments in synchrony would be seen, but that mothers would show adaptability. Twenty-five children (10 met ASD criteria on a gold standard autism assessment) completed a brief cognitive assessment and nine semi-structured play tasks with their mother, adapted from the Marschak Interaction Method. Synchrony was not found to moderate the relationship between ASD severity and externalizing behaviors, as hypothesized. ASD severity did predict externalizing behaviors. While children in the ASD group were more negative during the observed play tasks, there were no group differences on mother or dyad scores. Despite power limitations, our findings suggest important future directions for examination of mother and dyad mechanisms that better explain these differences. / Master of Science

During the last decade, the number of children diagnosed with Autism Spectrum Disorders (ASD) has increased and more and more children with ASD are educated in inclusive classrooms. Although their inclusion can have several benefits, teachers face some challenges. The main reason is these students’ problem behavior or lack of a desirable behavior. The aim of this systematic literature review was to analyze interventions for behavior management of students with ASD, since the ratification of Salamanca Statement and Framework for Action (UNESCO, 1994), in inclusive preschool and primary school classrooms. The aim was also to examine the outcomes of these interventions. Four databases were searched and nine articles were included for data extraction. Results indicated the implementation of different interventions such as function-based interventions, peer support, visual cue cards, structured teaching with graduated guidance, social stories and social scripts. The target behavior was principally assessed through Functional Behavioral Assessment (FBA) or it was not assessed at all. Some interventions were provided by the researcher or the teacher only, some were provided by different people in different phases and some were provided by two or more people together. Interventions’ goals were to decrease problem behavior, to increase desirable behavior and both to decrease problem behavior and to increase desirable behavior. It was observed that all interventions reached their goals, even though at a low level in some cases. In conclusion, this literature review provided a summary of interventions and their outcomes for behavior management of students with ASD in inclusive classrooms with a further purpose to help the teachers identify the strategies most useful for their classroom.

Les Troubles du Spectre Autistique (TSA) forment un groupe hétérogène de troubles neurodéveloppementaux caractérisés par des déficits de l’interaction sociale et de la communication ainsi que la présence de comportements répétitifs et d’intérêts restreints. Les TSA affectent environ un individu sur 68. Ils se manifestent généralement durant les trois premières années de vie mais, pour certains cas, les symptômes sont reconnus plus tard, quand les exigences sociales augmentent. Les études de jumeaux et la récurrence des troubles dans certaines familles démontrent l’importance des facteurs génétiques dans la vulnérabilité aux TSA. Cependant, l’architecture génétique des TSA reste difficile à caractériser car elle est extrêmement hétérogène et il est très compliqué d’identifier, pour chacun des patients, la combinaison d’allèles à risque. Notre laboratoire a identifié la première voie génétique associée aux TSA – la voie NLGN-NRXN-SHANK- qui joue un rôle clé dans la plasticité synaptique. Il existe un nombre de plus en plus grand de gènes associés aux TSA mais peu d’études ont été réalisées sur des cohortes épidémiologiques et dans des populations isolées. L'analyse des données de génotypage et de séquençage d’exome de 357 individus issus des îles Féroé (36 patients, 136 apparentés des patients, 185 témoins) nous a permis de mettre en évidence un nombre plus important de Variations du Nombre de Copies (CNVs), un coefficient de consanguinité supérieur, un plus grand nombre de mutations homozygotes et délétères ainsi qu’un Polygenic Risk Score (ASD-PRS) supérieur chez les patients TSA comparés aux individus témoins. Notre analyse confirme le rôle de plusieurs loci associés aux TSA (NRXN1, ADNP, délétion 22q11) et a permis d’identifier de nouvelles mutations tronquant la protéine (GRIK2, ROBO1, NINL et IMMP2L) ou récessives (KIRREL3 et CNTNAP2) affectant des gènes déjà associés aux TSA. Nous avons également mis en évidence trois nouveaux gènes candidats jouant un rôle important dans la plasticité synaptique (RIMS4, KALRN et PLA2G4A) à travers la présence de mutations de novo délétères chez des patients sans déficience intellectuelle. Au total, nous avons pu identifier une cause génétique expliquant les TSA pour 11% des patients et au moins une mutation fortement délétère dans des gènes candidats chez 39% des patients. Aucune cause génétique n'a pu être trouvée chez 50% des patients. En résumé, notre étude permet de mieux comprendre l’architecture génétique des TSA dans les populations isolées en soulignant à la fois l'impact des variants communs et des variants rares mais également en révélant le rôle de nouveaux gènes pour les TSA. Ces gènes codent pour des protéines essentielles pour le neurodéveloppement et l’identification de ces facteurs impliqués dans la formation et l'entretien des synapses pourrait ainsi fournir de nouvelles pistes afin de mieux comprendre les bases biologiques des TSA et de découvrir de nouvelles stratégies thérapeutiques. Il est cependant nécessaire de comprendre plus avant l'impact de la combinaison de différentes mutations sur la fonction neuronale afin de mieux caractériser l’architecture génétique des TSA. / Autism Spectrum Disorders (ASDs) are a heterogeneous group of neurodevelopmental disorders characterized by deficits in social interaction and communication as well as the presence of repetitive behaviors and restricted interests. ASD affects approximately one in 68 individuals. They usually occur during the first three years of life but, in some cases, symptoms are recognized later, when social demands increase. There is a strong genetic component to ASD, as indicated by the recurrence risk in families and twin studies. However, the genetic architecture of ASD remains largely unknown because of its extreme heterogeneity. It is very challenging to identify, for each patient, the combination of risk alleles. Our laboratory identified the first genetic pathway associated with ASD – the NLGN-NRXN-SHANK pathway – playing a key role in synaptogenesis during development. There are an increasing number of genes associated with ASDs but few studies have been conducted on epidemiological cohorts and isolated populations. Here, we investigated 357 individuals from the Faroe Islands including 36 patients with ASD, 136 of their relatives and 185 non-ASD controls. Data from SNP array and whole exome sequencing revealed that patients had a higher burden of copy-number variants, higher inbreeding status, higher load of homozygous deleterious mutations, and a higher ASD polygenic risk score compared to controls. We confirmed the role of several ASD-associated loci (NRXN1, ADNP, 22q11 deletion) and identified new truncating (GRIK2, ROBO1, NINL and IMMP2L) or recessive variants (KIRREL3 and CNTNAP2) affecting genes already associated with ASD. We have also identified three novel candidate genes playing key roles in synaptic plasticity (RIMS4, KALRN and PLA2G4A) carrying deleterious de novo mutations in patients without intellectual disability. Overall, for 11% of individuals with ASD, a known genetic cause was identified, for 39% at least one strongly deleterious mutation was identified in a compelling candidate gene and for 50% no obvious genetic cause was detected. In summary, our study provides a better understanding of the genetic architecture of ASD in isolated populations by highlighting both the impact of common and rare variants but also by revealing the role of new genes for ASD. These genes code for proteins that are essential for neurodevelopment. The identification of these factors involved in synapse formation and maintenance could provide new leads to better understand the biological basis of ASD and find novel therapeutic strategies. However, it is necessary to further understand the combined impact of different mutations on neuronal function in order to better characterize the genetic architecture of ASD.

The present study evaluated the use of a self-instructional manual supported by a computer-aided personalized system of instruction (CAPSI) for teaching Discrete-Trials Teaching (DTT) to university students. Prior to studying the manual, five participants taught three tasks, commonly taught to children with Autism Spectrum Disorders (ASD), to a confederate role-playing a child with an ASD. Using the Discrete-Trials Teaching Evaluation Form (DTTEF), the main researcher assessed the participants’ ability to perform DTT accurately. Subsequently, participants studied a self-instructional manual using CAPSI to demonstrate mastery of study questions about DTT. Finally, participants once again attempted to teach the three tasks to a confederate role-playing a child with an ASD. Overall mean baseline accuracy on the DTTEF was 54.86%, and improved to 84.73% in post-treatment, a 30% improvement. Participants’ self-recorded study time was an average of 12 hours and 48 minutes. The results suggest that CAPSI is an effective educational tool for the delivery of the self-instructional manual. Future research should investigate (1) how to make CAPSI even more effective, and (2) whether these results can be generalized to other populations such as ABA tutors, parents, and paraprofessionals working with children with ASD.

Several studies show that physical activity has positive effects for children with autism. Therefore, I chose to investigate the form of adaptions student in autism spectrum in the subject of sports and health and what conditions the physical education teachers have to create a favorable environment for student with autism. Through a qualitative research method with teachers in physical education and health, the material has been collected with semi structured interviews. The results show how teachers adapt teaching to student with autism spectrumdisorders. Physical education and health teachers work in different ways. The adaption can consist of preparation, the student’s special interests, structure, participation/involvement, andclarity in the teaching. Based on the discussion, all students are different and the teachers need to adapt the student’s needs. / Flertal studier visar att fysisk aktivitet har positiva effekter för barn med autism. Därför valde jag att undersöka vilken form av anpassningar elever inom autismspektrumet i ämnet idrott och hälsa och vilka förutsättningar idrottslärarna har för att skapa en gynnsam miljö för elever med autism. Genom en kvalitativ forskningsmetod med lärare inom idrott och hälsa har materialet samlats in via semistrukturerade intervjuer. I resultatet framkommer det hur lärarna anpassar undervisningen till elever med autismspektra. Idrott och hälsa lärarna arbetar på olika sätt för att anpassa undervisningen. Anpassningen kan bestå av förberedelser, elevensspecialintressen, struktur, delaktighet/involvering samt tydlighet i undervisningen. Utifrån diskussionen är alla elever olika och lärarna behöver anpassa elevens behov.

Des anomalies biochimiques de la voie sérotonine-N-acétylsérotonine-mélatonine ont été observées dans les Troubles du Spectre Autistique (TSA) et la prématurité. Cependant, les mécanismes moléculaires de régulation de cette voie et les causes des anomalies biochimiques observées dans ces maladies sont encore mal connus. Afin de mieux comprendre les bases génétiques de la voie sérotonine-N-acétylsérotonine-mélatonine, nous avons utilisé une approche de génétique quantitative au travers de deux populations d’étude indépendantes, dans lesquelles des paramètres de cette voie ont été mesurés. Ces deux cohortes, composées d’une part de plus de 250 familles avec autisme et plus de 300 témoins et d’autre part, de 183 nouveau-nés dont 93 nés très prématurés, incluent ainsi des individus présentant deux situations pathologiques différentes associées à des anomalies de cette voie. Une première étude de la voie sérotonine-N-acétylsérotonine-mélatonine dans les familles avec TSA a permis d’obtenir des estimations de l’héritabilité au sens strict, allant de 0,22 pour la mélatonine à 0,72 pour la N-acétylsérotonine (NAS). Des études d’association portant dans un premier temps sur une liste de 812 gènes candidats pour la régulation de la voie sérotonine-NAS-mélatonine et dans un second temps sur tout le génome, n’ont pas permis d’identifier des variants significativement associés aux traits biochimiques. Cependant, des études d’association par gènes ont permis d’identifier trois nouveaux gènes candidats (IL21R, JMJD7 et MAPKBP1) pour la régulation de cette voie dans les familles avec TSA ainsi qu’un nouveau gène (RAET1G) dans la cohorte de nouveau-nés prématurés et témoins. Enfin une étude biochimique des phénol-sulfotransférases (PST) dans les familles avec TSA a mis en évidence une faible activité enzymatique chez 29% des patients en comparaison avec les témoins (5ème percentile). Le séquençage et le génotypage du nombre de copies des gènes de la famille SULT1A1 n’ont pas permis d’identifier des variations génétiques associées aux TSA, à l’activité PST, ou aux taux de sérotonine et de mélatonine. En conclusion, ces résultats confirment la complexité de l’architecture génétique de la voie sérotonine-NAS-mélatonine. D’autre part, ils ont permis de mettre en évidence une héritabilité élevée de cette voie et d’identifier de nouveaux gènes candidats pour comprendre la diversité inter-individuelle de cette voie chez les personnes avec TSA, les enfants prématurés et la population générale. / Biochemical abnormalities of the serotonin-N-acetylserotonin-melatonin pathway have been reported in many clinical conditions such as Autism Spectrum Disorders and preterm birth. However, molecular mechanisms underlying this pathway regulation, as well as the causes of these biochemical abnormalities remain largely unknown. The aim of this study was thus to characterize the genetic basis of the serotonin-N-acetylserotonin-melatonin pathway. To do so, we used a quantitative genetic approach in two independent populations that were previously biochemically explored for this pathway. One cohort consisted of more than 250 families with ASD and more than 300 controls and the other was composed of 183 infants including 93 very preterm newborns. Both cohorts included individuals with clinical conditions associated with disruptions of the serotonin-N-acetylserotonin-melatonin pathway. Narrow sense heritability analysis of this pathway showed relatively high estimates, ranging from 0.22 for melatonin to 0.72 for N-acetyserotonin (NAS). First, candidate-gene association studies including 812 genes related to the serotonin-NAS-melatonin pathway, then genome-wide association studies were conducted. These analyses did not identify any variant associated at the genome-wide significance level. However, a gene-based approach identified three new candidate genes (IL21R, JMJD7 and MAPKBP1) for the regulation of the pathway in families with ASD as well as one gene (RAET1G) in the cohort of preterm and term newborns. Finally, a biochemical exploration of the phenol-sulfotransferases (PST) in families with ASD revealed a decreased enzyme activity in 29% of patients compared with controls (5th percentile). SULT1A1-4 genes were then sequenced and copy number variants (CNV) were genotyped. No genetic variant could be significantly associated with PST activity, melatonin and serotonin levels, or ASD status. In conclusion, these results confirm the complexity of serotonin-NAS-melatonin pathway genetic architecture. Furthermore, this study revealed high heritability of this pathway and identified new candidate genes to understand the inter-individual variability of this pathway in ASD, preterm birth and the general population.

Made available in DSpace on 2016-03-15T19:40:16Z (GMT). No. of bitstreams: 1 Daniel de Sousa Filho.pdf: 797124 bytes, checksum: b6136c0e2a983cf0eaad975c2f8445b7 (MD5) Previous issue date: 2014-02-06 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Background: Autism Spectrum Disorders (ASD) are developmental disorders characterized by qualitative impairment in reciprocal social interaction, language and communication and restricted, repetitive, and stereotyped patterns of behavior, interests, and activities and they are defined based on standardized clinical criteria as such those from international manuals as ICD and DSM, or based on clinical tools, mainly the semi-structured interviews, such as the Autism Diagnostic Interview- Revised (ADI-R), a recognized gold standard diagnostic tool for ASD. This interview was recently translated into brazilian Portuguese, and it was preliminarily validated for this language. However, this process has been occurred with a small sample in a specific state of Brazil. Besides, other validity evidences, as convergent validity were not explored in this study. Aim: The aim of this study was to investigate the Convergent Validity between the Brazilian version of the ADI-R and a screening tool Autism Behavior Checklist (ABC). Method: For this study, 20 parents or caregivers of children and teens diagnosed with ASD were recruited from the Presbyterian Mackenzie University ASD Clinic, and from the Federal of São Paulo State University Social Cognition Clinic. The children were submitted to a clinical multidisciplinary evaluation, and neuropsychological evaluation that also consisted on application of the ABC. Another researcher, a Child Psychiatrist with expertise on ASD was previously trained and allowed for conducting and codificating the ADI-R. Results: The age of the probands has ranged between 6 and 19 years old, 90% of them were male. The correlations between both the tools, using the Pearson coefficient were mostly positive, and they have ranged between average to high with statistical significance., considering the 3 mains domains of the ADI-R and the five main domains of the ABC. Conclusions: Evidence of convergent validity was found when comparing ADI-R results with ABC/ICA. / Introdução: Os Transtornos do Espectro do Autismo (TEA) são transtornos do desenvolvimento caracterizados por prejuízos qualitativos na interação social recíproca, comunicação e linguagem e pela presença de padrões de comportamentos estereotipados, restritos e repetitivos e sua caracterização se faz a partir de critérios clínicos definidos e padronizados por classificações internacionais como as da CID ou DSM ou por instrumentos, principalmente as entrevistas, como a Autism Diagnostic Interview-Revised (ADI-R), instrumento considerado pela literatura padrão-ouro para diagnóstico de TEA e que recentemente foi traduzido e preliminarmente validado para o português brasileiro. Entretanto, tal processo ocorreu com uma amostra reduzida e numa região específica do Brasil, assim como outras evidências de validade do instrumento tais como validade convergente não foram exploradas. Objetivo: Investigar evidências de validade de convergente entre a versão brasileira da entrevista diagnóstica ADI-R e os instrumento de triagem Inventário de Comportamentos Autísticos (ICA). Método: Foram selecionados 20 pais e/ou cuidadores de 20 sujeitos a partir da Clínica de TEA da Universidade Presbiteriana Mackenzie e da Universidade Federal de São Paulo. Os sujeitos foram submetidos à avaliação clínica multidisciplinar médica e neuropsicológica a qual incluía a aplicação do ICA. Um outro avaliador, psiquiatra da Infância e Adolescência com experiência em TEA e habilitado a aplicar a ADI-R foi responsável pela aplicação e codificação da entrevista. Resultados: A idade dos sujeitos variou de 6 a 19 anos, com média de 10,1. Desses, 90% eram do sexo masculino. Os coeficientes de correlação de Pearson entre os 3 domínios da ADI-R (comunicação, interação social e comportamentos restritos) entre si e destes com o e os do ICA (escrever todos), foram moderados e altos, positivos e a maioria com significância estatística. Conclusões: Evidências de Validade Convergente foram encontradas, comparando-se a ADI-R com o ABC/ICA.

Les Troubles du Spectre de l'Autisme (TSA) sont devenus une priorité nationale et internationale en matière de santé publique. À ce titre, de nombreux outils et différents types de prises en charge sont proposés avec plus ou moins de résultats pour les personnes qui en sont atteintes. C'est pourquoi, les dernières recommandations de la Haute Autorité de Santé (HAS, 2012) ainsi que le plan gouvernemental autisme 2013-2017 insistent sur l'importance de mener des études objectives concernant l'évolution et les prises en charge des personnes porteuses de TSA. Cette recherche qui comprend 2 études distinctes, vise à (1) objectiver l'efficacité d'un dispositif innovant d'intervention développementale en milieu ordinaire pour les personnes porteuses de TSA (le programme IDDEES : Intervention - Développement - Domicile - Ecole - Entreprise - Supervision) et à (2) démontrer le bénéfice de l'utilisation de nouvelles technologies (applications LearnEnjoy) associées à ce programme sur la dysrégulation fonctionnelle et les comportements restreints et répétitifs. Les participants de l'étude 1 sont des enfants âgés de 1 à 9 ans, ayant un TSA et bénéficiant tous du programme IDDEES (N = 51 enfants). Le diagnostic a été établi sur la base des critères du DSM-5 (APA, 2013) et de l'échelle d'évaluation quantitative, la CARS (Schopler, Reichler & Renner, 1988). Les enfants sont évalués à 3 temps différents (10 mois d'intervalle) sur le plan développemental (PEP-3, Schopler, Lansing, & Reichler, 2010 ; EDEI-R, Perron-Borelli, 1996 ; etc.) et comportemental (CARS, Schopler, et al., 1988). La population de l'étude 2 est constituée de 31 enfants et adolescents âgés de 3 ans à 17 ans et de 9 adultes âgés de 17 à 38 ans, bénéficiant du programme IDDEES et de l'utilisation des applications LearnEnjoy dans leur programme de remédiation. Tous les 3 mois durant 2 ans, les accompagnants de ces personnes cotent des échelles permettant d'analyser l'évolution de leur dysrégulation (GRAM, Adrien, 1996) et de leurs comportements répétitifs et restreints (EC2R, Bourreau, Gomot, Roux et Barthélémy, 2009). Les résultats de la 1ère étude mettent en évidence une évolution des âges de développement et une diminution de la symptomatologie autistique des personnes bénéficiant du programme IDDEES, indépendamment de l'âge réel et de l'intensité du trouble autistique au début de l'étude. Les résultats de la seconde, montrent que les personnes bénéficiant à la fois du programme IDDEES et des applications LearnEnjoy, après un temps d'adaptation nécessaire, parviennent à se réguler de mieux en mieux au fil des mois. De plus, leur comportements restreints et répétitifs et leur résistance au changement diminuent au profit d'une plus grande souplesse cognitive. Le programme IDDEES qui tient compte du développement atypique et du fonctionnement dysrégulé et si particulier des personnes avec TSA, constitue ainsi une bonne méthode pour favoriser leur développement et leur adaptation à l'environnement physique et social. Pour les professionnels respectueux de l'éthique et soucieux d'améliorer la qualité de vie de ces personnes, il est indispensable de proposer des interventions de qualité et reconnues comme telles. / Autism Spectrum Disorders (ASD) became a national and international public health priority. As such, many tools and different types of care are offered with varying degrees of success for those affected. That's why the latest recommendations of the High Authority for Health (HAS, 2012) and the governmental plan for autism 2013-2017 stress the importance of conducting objective studies on the evolution and care of people Carriers. This research, which includes 2 separate studies, aims to (1) objectify the effectiveness of an innovative device for developmental intervention in a standard environment for persons with ASD (Program' IDHSFS : Intervention-Development-Home-School-Firm-Supervision) and (2) show the benefit of using of new technologies (LearnEnjoy' applications) associated to this program on functional dyregulation and their repetitive and restricted behaviours. Participants of study 1, are children aged 1-9 years with ASD and all with Program' IDHSFS  (N = 51 children). The diagnosis was based on DSM-5 criteria (APA, 2013) and the quantitative assessment scale, CARS (Schopler, Reichler & Renner, 1988). Children were assessed at 3 different times (10 months apart), developmental evaluation (PEP-3, Schopler, Lansing, & Reichler, 2010, EDEI-R, Perron-Borelli) and behavioral evaluation (CARS, Schopler, & al, 1988). The study 2 population is constituted of 31 children and teenagers aged 3 to 17 years and 9 adults aged 17 to 38 years, benefiting from the Program' IDHSFS and the use of LearnEnjoy' applications in their weekly socio-cognitive rehabilitation sessions. Every three months, for 2 years, expert in autism coaches of these people established some scales allowing to analyze the evolution of their activity's regulation (RAMG, Adrien, 1996) and their repetitive and restricted behaviours. (EC2R, Bourreau, Gomot, Roux and Barthélémy, 2009). The results of the first study shows an evolution of the developmental ages and a decrease in the autistic symptomatology of people benefiting from the IDDEES program, regardless of the real age and intensity of the autistic disorder at the start of the study. The results of the second, show that people benefiting from both the Program' IDHSFS and the LearnEnjoy' applications, after a necessary period of adaptation, manage to regulate better and better over the months. Moreover, their repetitive and restricted behaviours, and their resistance to change decreases in favor of greater mental flexibility. The IDDEES program, which takes into account the atypical development and the dysregulated functioning of people with ASD, is a good method for their development and adaptation to the physical and social environment. For professionals who respect ethical standards and are keen to improve the quality of life of these people, it is essential to offer high-quality and recognized interventions.

TITLE: Developing Communication Skills in Children with Autism Using Verbal Behavior - Applied Behavior Analysis AUTHOR: Bc. Kateřina Chrapková DEPARTMENT: The Department of Special Education SUPERVISOR: doc. PaedDr. Jiřina Klenková, Ph.D. ABSTRACT: This thesis deals with the development of communication skills in children with autism using Verbal Behavior - Applied Behavioral Analysis (VB-ABA). The aim of this work is to introduce VB-ABA approach as an effective intervention for people with Autism Spectrum Disorders (ASD). It is a monographic work with emphasis on a theory. The empirical part consist evaluative single-case study. The thesis is devided into six theoretical and one empirical chapter. The first theoretical chapter presents the issue of communication in a view of behaviorism and compares this approach with classical linguistics. The second chapter describes theories of language acquisition and language development from behavioral and linguistic perspective. The third chapter discusses the development of children's speech in the context of ontogeny and its functions. The fourth chapter deals with the issue of communication skills in the context of ASD. The fifth chapter introduces evidence based practice and provides information on current international research of interventions for persons...