Os transtornos do espectro autista (TEA) são condições neuropsiquiátricas caracterizadas por padrões comportamentais estereotipados, ausência ou limitação de comunicação verbal e de interação social recíproca. Diversos estudos têm mostrado que esses transtornos possuem etiologia genética complexa e heterogênea, o que dificulta a identificação dos fatores causais. Estima-se que cerca de 70% dos casos de TEA são idiopáticos. Portanto, com o objetivo de identificar mecanismos etiológicos associados aos TEA, utilizamos as seguintes estratégias: customização de uma lâmina de microarray CGH que possibilite a detecção não só de grandes CNVs, mas também de alterações menores do que 10 kbp, em exons e regiões UTR de genes potencialmente candidatos; a comparação entre os tipos de rearranjos detectados em pacientes sindrômicos e em não sindrômicos e, ainda, a investigação mais detalhada de uma família com indivíduos portadores de transtorno autista e síndrome de Asperger. Foram avaliados 103 portadores de TEA não sindrômicos e 18 sindrômicos, sendo as taxas de detecção de alterações potencialmente patogênicas, respectivamente, de 11,6% e 38,9%. Dentre as alterações detectadas 44,4% são menores do que 10 Kbp. Portanto, a estratégia de usar uma lâmina customizada, com alta densidade de sondas complementares aos exons e regiões não codificantes de genes potencialmente envolvidos na etiologia dos TEA, capaz de detectar tanto alterações grandes quanto pequenas, parece ser relevante na tentativa de elucidar o maior número de casos possíveis e melhor compreender esses transtornos. Além disso, essa lâmina também pode ser utilizada como uma ferramenta para auxiliar o diagnóstico clínico e o aconselhamento genético com um custo mais acessível em comparação a outras comerciais ou ao sequenciamento de última geração. Cerca de 33,3% das CNVs observadas afetam região UTR, sugerindo que mutações nessas regiões podem explicar uma proporção significativa dos casos nos quais não são detectadas alterações através de outros testes genômicos, visto que a maioria desses ainda não exploram adequadamente regiões não codificantes. Entre os pacientes autistas não sindrômicos verificou-se que a maioria dos genes afetados por CNVs estão envolvidos em duas principais funções biológicas - sinapses glutamatérgicas e orientação axonal, sugerindo que TEA não sindrômico pode ser causado por disfunção em genes diferentes envolvidos em processos fisiológicos comuns. Diferente do que observamos entre pacientes não sindrômicos, detectamos mais de uma alteração em um mesmo indivíduo ou alterações que englobam mais de um gene entre os pacientes sindrômicos, reforçando o modelo oligogênico para alguns casos de TEA. Por fim, os dados obtidos no estudo da família com portadores de síndrome de Asperger e transtorno autista sugere que a gravidade do quadro clínico possa estar relacionada ao número de mutações e possivelmente por duas mutações diferentes em ambos os alelos de um mesmo gene. Nossos resultados, além de apoiar o envolvimento dos genes MDGA2, FHIT, HTR2A, SHANK2, GRIA3, ZNF778, PRKCα, CDH15, DIAPH3, GCH1, GRM5, MARK1, SLC17A6, IMMP2L, BZRAP1, SYNGAP1, ANK3, MAP1A, GABRR2 e LAMC3 nos TEA também sugere novos genes candidatos: LRRC7, LRRIQ3, CADPS1, NUFIP, SEMA3A, SNAP29, MBD2, GAD2, DGKH e PARD3 / The autism spectrum disorders (ASD) are neuropsychiatric conditions typically characterized by social deficits, communication difficulties, stereotyped or repetitive behaviors and interests. Several studies have shown that these disorders have a complex and heterogeneous genetic etiology, which makes difficult to identify the causal factors. Approximately 70% of cases are idiopathic. In order to identify etiological mechanisms associated with ASD, we have used the following strategies: customized a microarray CGH platform that allows detection not only of large CNVs, but also alterations smaller than 10 kbp in exons and UTR regions of potential candidate genes, the comparison between the types of rearrangements detected in syndromic and non-syndromic patients and further, more detailed investigation of a family segregating both autistic disorder and Asperger syndrome. We evaluated 103 nonsyndromic and 18 syndromic patients by the custom-designed array and the detection rate of possibly pathogenic alterations were, respectively, 11.6% and 38.9%. Among these CNVs, 44.4% are smaller than 10 kbp. Therefore, the strategy of using a custom-designed array, enriched with probes targeted to genes potentially involved in the ASD etiology and able to detect both large and small CNVs, seems to be relevant in an attempt to elucidate the largest number of cases and to better understand these disorders. Furthermore, this platform can also be used as a tool to support the clinical diagnosis and genetic counseling with a more affordable cost compared to conventional other or next-generation sequencing. Approximately 33.3% of the observed CNVs affect UTR region, suggesting that mutations in non-coding regions might explain a significant proportion of ASD cases negative for most genomic screenings, which still do not explore adequately these regions. Among nonsyndromic autistic patients we found that most of the genes affected by CNVs are involved in two main biological functions - glutamatergic synapses and axonal guidance, suggesting that nonsyndromic ASD can be caused by dysfunction in different genes of a few common physiological processes. In contrast to our findings in nonsyndromic patients, we detected more than one alteration in a single individual or alterations that involve more than one gene among the syndromic patients, reinforcing the oligogenic model for some cases of ASD. Finally, the data obtained in the study of the family segregating both Asperger syndrome and autistic disorder suggests that the severity of ASD seems to be modulated by the number of hits and possibly by hits in both alleles of the same gene. Our results support the involvement of genes MDGA2, FHIT, HTR2A, SHANK2, GRIA3, ZNF778, PRKCα, CDH15, DIAPH3, GCH1, GRM5, MARK1, SLC17A6, IMMP2L, BZRAP1, SYNGAP1, ANK3, MAP1A, GABRR2 and LAMC3 in ASD etiology and also suggests new candidates: LRRC7, LRRIQ3, CADPS1, NUFIP, SEMA3A, SNAP29, MBD2, GAD2, DGKH and PARD3

Introdução: os transtornos do espectro autista (TEA) representam uma desordem comportamental complexa, com etiologias múltiplas e diferentes níveis de severidade. Indivíduos com TEA compreendem e expressam melhor a comunicação não verbal na presença da música. A musicoterapia improvisacional é uma das principais abordagens nesse campo para avaliar as habilidades de comunicação não verbal. Justificativa: a música se torna uma ferramenta relevante para avaliar a comunicação não verbal em pessoas com TEA, principalmente relacionada à musicoterapia improvisacional. No entanto, não há instrumentos de avaliação da musicoterapia improvisacional validados para esse fim. Objetivos: verificar os efeitos da improvisação musical em desfechos oriundos de ensaios controlados randomizados (ECRs) através de uma revisão sistemática. Ainda, traduzir e validar para uso no Brasil um instrumento específico de musicoterapia que avalia a comunicação de crianças com autismo: o Category System for Music Therapy (KAMUTHE). Metodologia: na revisão sistemática, foram analisados ECRs entre os anos de 1989 e 2011 a partir da busca em 13 bases de dados. A tradução e validação da KAMTUHE foi realizada através de um estudo transversal e analisou as propriedades psicométricas de validade de conteúdo, validade discriminante, validade convergente e concordância entre avaliadores. Resultados: a revisão sistemática verificou que 67% dos desfechos foram favoráveis a improvisação musical em comparação com a situação controle. No estudo de validação, as propriedades psicométricas apresentaram resultados satisfatórios. Conclusões: a revisão sistemática mostrou que a improvisação musical foi superior às intervenções controle. Entretanto, não foi possível verificar a dimensão desta intervenção pela ausência do cálculo da metanálise. As propriedades psicométricas encontradas no estudo de validação habilitam a versão brasileira do KAMUTHE para uso no Brasil. / Introduction: the autism spectrum disorders (ASD) represent a complex behavioral disorder with multiple etiologies and different levels of severity. Individuals with ASD understand and express better non-verbal communication in the presence of music. The improvisational music therapy is one of the main approaches in this field to assess the skills of non-verbal communication. Justification: the music becomes a relevant tool to assess non-verbal communication in people with ASD, mainly related to improvisational music therapy. However, here is no assessment instruments of improvisational music therapy validated for this purpose. Objectives: to assess the effects of musical improvisation on outcomes from randomized controlled trials (RCTs) through a systematic review. Moreover translate and validate for use in Brazil a specific music therapy assessment that evaluates the communication of children with autism: the Category System for Music Therapy (KAMUTHE). Methodology: in the systematic review, it were analyzed RCTs between the years 1989 and 2011 from the search in 13 databases. The translation and validation of KAMTUHE was performed using a cross-sectional study examined the psychometric properties of content validity, discriminant validity, convergent validity and inter-rater agreement. Results: the systematic review found that 67% of the outcomes were favorable musical improvisation in comparison with the control situation. In the validation study, the psychometric properties showed satisfactory results. Conclusions: The systematic review demonstrated that musical improvisation was superior to control interventions. However, it was not possible to verify the dimension of this intervention by the absence of the meta-analysis estimate. Psychometric properties found in the validation study enable the Brazilian version of KAMUTHE for use in Brazil.

Made available in DSpace on 2015-04-11T14:02:55Z (GMT). No. of bitstreams: 1 david lima.pdf: 2199406 bytes, checksum: 3671a666ea48250faadbd05a2d26e54b (MD5) Previous issue date: 2013-02-28 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / O objetivo desta dissertação é contribuir para as formas de reabilitação cognitiva e social em crianças com Transtornos do Espectro do Autismo (TEA), fornecendo suporte computacional adequado a sessões de musicoterapia em que a criança já esteja se preparando para ser incluída em grupos de musicalização infantil. Isto será realizado através da prototipação de um aplicativo para o dispositivo móvel iPad para a apreciação e produção musical, seguindo o processo de desenvolvimento incremental com design de interface participativo. Espera-se, com isso, contribuir não só para o aprimoramento das habilidades musicais das crianças como também para o desenvolvimento de sua organização cognitiva e espacial. A musicalização com suporte computacional é importante, pois utiliza-se de recursos triviais, como sons, música, voz e instrumentos musicais, propiciando os indivíduos com TEA aprimorarem suas habilidades sociais, emocionais, cognitivas e de comunicação.

Made available in DSpace on 2016-03-15T19:39:59Z (GMT). No. of bitstreams: 1 Patricia Fukuda de Siqueira Baptista.pdf: 1719530 bytes, checksum: 6206faad33c0cdff7d8d996720499582 (MD5) Previous issue date: 2013-02-07 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Autism Spectrum Disorder (ASD) are a heterogeneous group of syndromes characterized by impairment in social interaction, impairment in communication and a pattern of repetitive or stereotyped behaviors. Gastrointestinal disorders and associated symptoms are commonly reported in individuals with ASDs, but key issues such as the prevalence and best treatment of these conditions are not fully understood. The main objective of this study was to investigate gastrointestinal symptoms (GS) in individuals with Autism Spectrum Disorder, check its frequency and possible relation to serum levels of serotonin, eating habits and medication use. The sample consisted of 100 children / adolescents diagnosed with ASD aged 3 to 21 years old. For determination of gastrointestinal symptoms was used a questionnaire that assesses the presence and frequency of gastrointestinal disorders. The dosage of serotonin serum was determined by high performance liquid chromatography, dietary was assessed by food frequency questionnaire. The results showed that 42% of the participants had some type GS, being constipation the most often (31% of cases). It was found a correlation between severity of ASD and GS. In the analysis of serotonin hyperserotonemia was verified in 19% of patients and did not show correlations between dietary, use of medications and GS. / Transtornos do Espectro do Autismo (TEA) são um conjunto heterogêneo de síndromes caracterizadas por prejuízos nas interações sociais, deficiência na comunicação e um padrão de comportamentos repetitivos ou estereotipados. Doenças gastrointestinais e sintomas associados são comumente relatados em indivíduos com TEA, mas questões centrais como prevalência e melhor tratamento destas condições não são totalmente compreendidas. O objetivo principal deste estudo foi investigar os sintomas gastrointestinais (SGI) em indivíduos com Transtornos do Espectro do Autismo, verificar a sua frequência e possível relação com os níveis séricos de serotonina, hábitos alimentares e uso de medicamentos. A casuística foi composta por 100 crianças/adolescentes diagnosticados com TEA com idade entre 3 e 21 anos. Para determinação dos sintomas gastrointestinais foi utilizado um questionário que avaliou a presença e a frequência dos distúrbios gastrointestinais. A dosagem de serotonina sérica foi determinada pelo método de cromatografia líquida de alta eficiência e a dieta alimentar foi avaliada pelo questionário de frequência alimentar. Os resultados mostraram que 42% dos participantes apresentaram algum tipo de SGI, sendo a constipação o mais frequente (31% dos casos). Foi evidenciada uma correlação entre gravidade do TEA e sintomas gastrointestinais. Na análise de serotonina foi verificada a hiperserotonemia em 19% dos pacientes e não foram evidenciadas correlações entre dieta alimentar, uso de medicamentos e SGI.

La neurohormone ocytocine (OT) est de plus en plus étudiée pour son potentiel thérapeutique dans les troubles du comportement social, comme l'autisme, qui sont associés à une dérégulation de plusieurs systèmes de neurotransmission, notamment l'OT et la sérotonine (5-HT). Dans ce cadre, une étape importante afin de développer des médicaments basés sur des mécanismes biologiques est de caractériser les interactions entre l'OT et les autres neurotransmetteurs. La littérature sur les rongeurs montre que la relation entre OT et 5-HT est fortement impliquée dans plusieurs aspects du comportement social. Par ailleurs, nous avons récemment montré chez le sujet sain que le fonctionnement du récepteur 5-HT 1A (5-HT1AR) est modifié suite à l'administration d'OT.neuroJ'ai donc réalisé une première expérience chez des patients autistes en utilisant le scanner TEP avec le radiotraceur [18F]MPPF (spécifique du 5-HT1AR). Aucune différence n'est apparue, à l'état basal, entre 18 patients autistes et 24 sujets contrôles. Par ailleurs, l'OT n'a pas modifié le système 5-HT1AR. Enfin, alors qu'une corrélation entre la densité de 5-HT1AR et le volume de matière grise du striatum a été observé dans le groupe contrôle, cette relation était absente dans le groupe de patients. Ces résultats suggèrent une altération subtile du 5-HT1AR, ne pouvant être détectée qu'au niveau fonctionnel.Parce que le scanner TEP ne permet pas de dire si les changements observés sont dus à une libération de sérotonine ou à une modification directe du récepteur, j'ai réalisé une deuxième expérience chez 3 macaques rhésus, avec le [18F]MPPF et le [11C]DASB (marquant le transporteur de la 5-HT). Par rapport au placebo, l'OT injectée dans le ventricule latéral a significativement augmenté la liaison du [18F]MPPF dans l'amygdale et l'insula tandis que la liaison du [11C]DASB diminuait dans ces mêmes régions. Ainsi, nous pouvons dire que l'OT a provoqué la libération de 5-HT ainsi qu'une modification du 5-HT1AR dans ces régions importantes pour les comportements socio-émotionnels. Une étude par autoradiographie a confirmé cette interprétation.Ces expériences montrent qu'il existe une action régulatrice de l'OT sur la 5-HT chez le primate, mais que ce mécanisme est dérégulé chez les patients avec autisme. Cela ouvre donc la voie à l'investigation de traitements combinés exerçant un effet sur ces deux neurotransmetteurs / The neurohormone oxytocin (OT) is increasingly studied for its therapeutic potential in social disorders, like autism, which are associated with the deregulation of several neurotransmission systems, including OT and serotonin (5-HT). Hence investigating OT’s interactions with other neurotransmitters is a relevant step towards mechanism-based treatments. Studies in rodents demonstrated that the interaction between OT and 5-HT, is critical for several aspects of social behaviour. Moreover, using PET-scan in humans we have recently found that 5-HT 1A receptor (5-HT1AR) function is modified after intra-nasal oxytocin intake. Thus I performed a first experiment in which intra-nasal OT was administered to patients with autism undergoing a [18F]MPPF (a 5-HT1AR radiotracer) PET scanner, in order to study their basal serotonergic system and to look if the oxytocin modulates the 5-HT1AR system. I found no differences of baseline 5-HT1AR concentration between 18 autistic subjects and 24 controls. Critically, in patients, OT did not induce changes on the 5-HT1AR system. Moreover, in controls, there was a correlation between 5-HT1AR and grey matter volume in the striatum, that was not observed in patients. These results suggest a subtle disruption of patients’ serotonergic system, that can only be seen at the functional level. Because PET scan does not tell us if the observed modification is due to a change in 5-HT1AR or 5-HT concentration, I performed a second PET scan experiment on 3 macaque monkeys, using [18F]MPPF and [11C]DASB, that marks the serotonin transporter. Compared to placebo, OT injections in the lateral ventricle significantly reduced [11C]DASB binding potential in right amygdala, insula and hippocampus whereas [18F]MPPF binding potential increased in right amygdala and insula. Thus we reproduced results obtained in healthy humans and extended it by suggesting that OT provokes the release of 5-HT in key limbic regions involved in socio-emotional processing. These results were confirmed with autoradiography.Taken together, these experiments indicate that OT modulates 5-HT release in primates, but this mechanism is disrupted in patients with autism. This opens ways to investigate combined OT/5-HT treatments, especially since FDA approved drugs targeting the two systems are already available for use in patients with autism

Autism Disorder and related disorders such as Asperger's Syndrome and Pervasive Developmental Disorder, Not Otherwise Specified, are collectively known as Autism Spectrum Disorders (ASD). These disorders are currently the fastest growing diagnosed disorders among children and have been found in 110 in 10,000 individuals. Individuals with ASD are delayed in social development according to diagnostic criteria. To address the social development delays of students with ASD, two research-based interventions have been developed: Social StoriesTM and video modeling. Social StoriesTM uses a specific combination of sentences to describe a social situation or a social skill in story form. Video modeling is an isolation of social skill steps delivered through a video medium to model the social skill. The purpose of this study was to combine Social StoriesTM and video modeling (combined intervention) and investigate the perceptions of educational multidisciplinary team members (school counselors, parents, teachers) regarding the combination intervention for the development of social behavior in students with ASD. School counselors participating in this study delivered the combination Social StoriesTM and video modeling intervention to student participants with ASD. Then, the perceptions of the school-based multidisciplinary team members of this combination intervention were collected through qualitative surveys and analyzed to develop the Qualitative Criticism. This Qualitative Criticism describes, interprets, and evaluates the pragmatic use of the combination of the Social StoriesTM and video modeling intervention with students with ASD in schools from the perspectives of the school counselors, teachers, and parents of these students. Organized by case, team members of each of the student participants reflected on the strengths and weaknesses of these interventions for that student. Across cases, comments were analyzed by role (i.e., parent, teacher, school counselor). Then, these roles were combined into a cross-case analysis of multidisciplinary team perspectives of the usefulness of these interventions for students with ASD. Pre-test and post-test data were collected using teachers' responses to the Vineland II Teacher Rating Form (V-II TRF) and the Summary of Observations section on the V-II TRF to triangulate findings grounded in the qualitative data. Findings suggested that parents, teachers, and school counselors supported the use of these interventions for several reasons. The combination intervention increased opportunities for repetition of the target skills; for visual learning through written words in stories, cartoons, and videos; and for individualization to meet the varying needs and interests of students with ASD. The intervention was also developmentally appropriate, engaging, and fun for students. In addition, when the school counselor collaborated with parents and teachers through the intervention, the parents and teachers seemed to be more knowledgeable about the intervention, and supported these students to use the intervention and generalize the target skills. While V-II TRF scores did not show statistically significant gains to confirm the multidisciplinary team members' support for the combination intervention, clinical significance was found in the domain scores of Communication and Daily Living, and in the Composite score measuring overall adaptive functioning.

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.

Self-monitoring involves teaching students to be aware of their own behavior, and be able to record whether the behavior happened or not. The present study uses meta-analysis of single case design (SCD) studies to evaluate the effectiveness of self-monitoring interventions that use electronic devices during implementation for individuals with autism spectrum disorder (ASD). Eligible studies were accessed to determine design quality, and examine the use of self-monitoring for individuals diagnosed with ASD. Studies were evaluated against inclusion-exclusion criteria. The studies that met inclusion criteria (n = 15) were assessed with the What Works Clearinghouse (WWC) standards for methodological rigor. The WWC standards were applied to baseline and intervention phases. There were a total of 12 studies with 32 students diagnosed with ASD that met SCD standards without, and with reservations. The 12 studies were evaluated using the Tau-U effect size metric to quantify the percentage of change that was attributed to the self-monitoring intervention. Overall, omnibus Tau-U was 0.96 (95% confidence interval [CI] = [0.89, 1.0]). Limitations and directions for future research are discussed.

(in English): The topic of the diploma thesis is the needs of people who informally take care of their close autism spectrum disorders. The aim of the work is to find out whether informal carers are systematically disadvantaged, whether the current system of help and support for these people is sufficient, accessible and clear and what would work differently from the point of view of these people to continue caring for their loved ones in the natural environment. The work defines the basic concepts, describes the specific care of people with autism spectrum disorders. It also presents available services and support for these informal carers and performs at some systemic disadvantage of these people. The practical part of the work contains a quality survey with informally caring people. This survey can show the specific needs of these people, how to change these personal orientations in the system of services and support, what from their point of view it would be good to do differently, what would help them situation, from the beginning of caring for a loved one with autism spectrum disorders. All this focuses on informally caring people from the Central Bohemian Region and Prague.

This applied dissertation was designed to provide online multimedia training materials for parents of children, ages 2-11, with Autism Spectrum Disorders (ASD), who use or need Augmentative and Alternative Communication (AAC). Many children with ASD have communication difficulties, and the best path to communication competence is through some form of AAC. Parents can have an enormous impact on their children’s ability to learn and use AAC effectively. By implementing a few supportive strategies, they can help their children become successful communicators. Implementing strategies in a home-based learning environment is important to provide generalization of skills across settings. Typically, parents do not have access to AAC learning materials to facilitate their child’s AAC learning and language growth. Barriers to accessing this material may be time, accessibility, stress, transportation, or financial constraints. Online education is becoming increasingly more popular and is looked upon as a means to obtain information in an efficient manner. Using specific AAC strategies to enhance receptive and expressive language, parents will be taught how to increase their child’s language skills during this natural routine. Along with input from content-area experts, training materials have been created to help parents better understand ways to support AAC learning at home. Parent participation allows for the materials, which focus on two key strategies, Aided Language Stimulation (ALgS) and Communication Temptations, to be field tested. The information provided by the content experts resulted in changes to the online multimedia training materials in order to determine content validity, evaluate the design, and assess the feasibility. The results indicated that the participant’s knowledge and self-efficacy did significantly increase from the pretest to the posttest after completing the online multimedia training materials. Additionally, the participant’s self-efficacy from The Usage Rating Profile – Intervention Revised (URP-IR) significantly increased after viewing the online multimedia training materials and the URP-IR is a reliable assessment to utilize when measuring self-efficacy.