Individuals with autism spectrum disorders (ASDs) are impaired in cognitive processes and emotional regulation, and exhibit stereotyped behaviours. Dopamine (DA) modulates executive functions, learning, memory, emotional processing and social cognition; all of which are impaired in individuals with ASDs. Because DA modulates a number of processes that are impaired in individuals with ASDs, genes in the dopaminergic pathway are good candidates for genes influencing autistic behaviours. As our previous findings suggested a role for a dopamine-related gene in families with only affected males, this thesis describes a comprehensive study of five genes affecting DA synthesis, levels and function in mothers and affected males with ASDs in an initial TEST cohort of 112 male-only affected sib-pair families as well as a replication study in three additional male-only family cohorts. I genotyped three to five polymorphisms in the TH, SLC6A3, DRD1, DRD2 and PPP1R1B genes and performed population-based single marker case-control comparisons, family-based association tests, quantitative transmission disequilibrium tests as well as haplotype-based analyses and tests for gene-gene interactions. I found evidence for association of the DRD1 (P=0.0027-0.040), DRD2 (P=0.0002-0.007) and PPP1R1B (P=0.00042-0.001) genes with autism in affected males from the TEST cohort. Evidence for DA-related gene interactions were found between polymorphisms in DRD1, DRD2 and PPP1R1B (P=0.0094-0.012) in affected males relative to a comparison group. Furthermore, I found that polymorphisms in the TH and DRD1 genes were associated with the risk for mothers having sons with ASD in the TEST families (P=0.007-0.025) and putative risk alleles in DRD1 and DRD2 were preferentially transmitted from mothers (P=0.016) and fathers (P=0.023) respectively, to affected children. All findings remained significant following corrections for multiple testing. The TEST cohort findings were not replicated in other family cohorts. However, an examination of dysmorphology data for the different family sets revealed phenotypic differences and thus, genetic differences are to be expected. In summary, I found evidence for a contribution of DA-related genes in a specific family cohort with ASDs. Additional functional and phenotypic studies will enable a better understanding of the contributions and implications of these findings to our understanding of autism. / Thesis (Ph.D, Physiology) -- Queen's University, 2009-03-18 13:58:12.223

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Doctor of Philosophy / This study defines Theory-of-Mind as the ability to experience one’s own mind and understand the minds of others to the extent necessary to make sense of human behaviour and the world. Since the concept of Theory-of-Mind was first applied to people with ASD (Baron-Cohen, Leslie & Frith, 1985), lack of Theory-of-Mind has been used to explain their cognitive difficulties (National Research Council, 2003), along with social, communicative and imaginative impairments (Frith, Happé & Siddons, 1994). Previous studies have tended to think of Theory-of-Mind in terms of a simple binary of deficit or credit; to exclude the voices of people with ASD; to emphasise the cognitive aspects of Theory-of-Mind over its affective aspects; and to emphasise understanding the minds of others over experiencing one’s own mind. This study aims to address these issues by investigating Theory-of-Mind as subjectively experienced by students with ASD and objectively understood by their teachers. It is the first attempt in the study of Theory-of-Mind to include the voices of individuals with ASD along with the professional views of their teachers. This study takes an interdisciplinary approach, supported by philosophy of mind and special education. A grounded theory approach and a mixed methods research design combine to build and strengthen a theory of Theory-of-Mind. For Theory-of-Mind as subjectively experienced, 20 senior secondary and post secondary school students with ASD from Republic of Korea were interviewed and student-produced documents were reviewed to draw out their inner experiences. The Korean Wechsler Adult Intelligence Scale and the Korean Vineland Social Maturity Scale were employed to assess IQ and social competence. For Theory-of-Mind as objectively understood, their teachers’ beliefs regarding their students with ASD were sought through in-depth interviews, a review of teacher-produced documents and administration of a newly developed Teacher Questionnaire. This study reports differences between Theory-of-Mind as subjectively experienced and objectively observed, and variations within the components of Theory-of-Mind. The role of imagination in Theory-of-Mind and the relationships between Theory-of-Mind components, IQ and social competence are discussed. As a result, a Theory-of-Mind continuum model and Theory-of-Mind Typology is proposed.

Doctor of Philosophy / This study defines Theory-of-Mind as the ability to experience one’s own mind and understand the minds of others to the extent necessary to make sense of human behaviour and the world. Since the concept of Theory-of-Mind was first applied to people with ASD (Baron-Cohen, Leslie & Frith, 1985), lack of Theory-of-Mind has been used to explain their cognitive difficulties (National Research Council, 2003), along with social, communicative and imaginative impairments (Frith, Happé & Siddons, 1994). Previous studies have tended to think of Theory-of-Mind in terms of a simple binary of deficit or credit; to exclude the voices of people with ASD; to emphasise the cognitive aspects of Theory-of-Mind over its affective aspects; and to emphasise understanding the minds of others over experiencing one’s own mind. This study aims to address these issues by investigating Theory-of-Mind as subjectively experienced by students with ASD and objectively understood by their teachers. It is the first attempt in the study of Theory-of-Mind to include the voices of individuals with ASD along with the professional views of their teachers. This study takes an interdisciplinary approach, supported by philosophy of mind and special education. A grounded theory approach and a mixed methods research design combine to build and strengthen a theory of Theory-of-Mind. For Theory-of-Mind as subjectively experienced, 20 senior secondary and post secondary school students with ASD from Republic of Korea were interviewed and student-produced documents were reviewed to draw out their inner experiences. The Korean Wechsler Adult Intelligence Scale and the Korean Vineland Social Maturity Scale were employed to assess IQ and social competence. For Theory-of-Mind as objectively understood, their teachers’ beliefs regarding their students with ASD were sought through in-depth interviews, a review of teacher-produced documents and administration of a newly developed Teacher Questionnaire. This study reports differences between Theory-of-Mind as subjectively experienced and objectively observed, and variations within the components of Theory-of-Mind. The role of imagination in Theory-of-Mind and the relationships between Theory-of-Mind components, IQ and social competence are discussed. As a result, a Theory-of-Mind continuum model and Theory-of-Mind Typology is proposed.

Thesis (Ph. D.)--Auburn University. / Abstract. Includes bibliographical references (p. 80-87).

Thesis (Ph. D.)--West Virginia University, 2009. / Title from document title page. Document formatted into pages; contains xii, 170 p. : ill. (some col.). Includes abstract. Includes bibliographical references (p. 93-112).

Title from title page (viewed April 28, 2010) Bouvé College of Health Sciences. Dept. of Counseling and Applied Educational Psychology. Includes bibliographical references (p. 167-176).

Les TSA représentent un groupe de troubles neurodéveloppementaux défini par des déficits des interactions sociales, de la communication et des comportements restreints et répétitifs. A ce jour le diagnostic de l’autisme se fait uniquement sur la base de symptômes cliniques. Il n’existe aucun biomarqueur des TSA. Ce travail s’inscrit donc (1) dans la recherche de biomarqueurs prédictifs dans les TSA et (2) dans la mise en évidence des dysfonctions métaboliques cérébrales dans un modèle de rat (rat valproate, VPA). Pour mettre en évidence des biomarqueurs urinaires prédictifs nous avons analysé simultanément les données issues de plusieurs technologies analytiques afin d’améliorer la robustesse et la capacité prédictive des modèles statistiques. L’autre partie de la thèse consistait à caractériser et à comparer au cours du développement l’évolution du métabolome du rat VPA. Nous avons mis en évidence des perturbations des voies de la neurotransmission, énergétique, du stress oxydatif etc. Même si on ne peut pas transposer les résultats obtenus chez le rat, à l’homme, le modèle VPA permet néanmoins de mieux comprendre les perturbations physiologiques cérébrales induites par ce médicament. / ASDs are a group of neurodevelopmental disorders defined by deficits in social interaction, communication and restricted and repetitive behaviors. To date, the diagnosis of autism is made only on the basis of clinical symptoms. There is no biomarker of ASD. The aim of this work is (1) the search of predictive biomarkers in ASD and (2) the better understanding of brain metabolic dysfunctions in a rat model (valproate rat, VPA). To highlight urinary predictive biomarkers we analyzed together data from different analytical technologies in order to improve the robustness and predictive power of statistical models. The second part of the thesis was to characterize and compare the cerebral metabolome of VPA rat during development. We showed disturbances of neurotransmission, energy, oxidative stress pathways. Even if results obtained in rats cannot be transposed to humans, the VPA model still allows a better understanding the brain physiological disturbances induced by the drug.

Orientador: Olga Maria Piazentin Rolim Rodrigues / Banca: Morgana de Fatima Agostini Martins / Banca; Sadão Omote / Resumo: O Transtorno do Espectro Autista (TEA) pode ser definido como um transtorno do desenvolvimento neurológico com base genética, identificável na primeira infância, com prejuízo persistente na comunicação social, presença de padrões restritos e repetitivos de comportamento, interesses ou atividade, que limitam e prejudicam o desenvolvimento do indivíduo (APA, 2014). Este estudo parte do pressuposto que conhecer as características do TEA possibilita a identificação precoce dos seus sinais e, consequentemente, o encaminhamento de crianças para uma avaliação especializada. Dentro desta perspectiva, esta pesquisa teve como objetivo investigar e descrever o conhecimento e a experiência de profissionais da educação infantil com crianças com TEA e, elaborar, implementar e avaliar a eficácia de um programa desses profissionais para a identificação precoce de sinais do transtorno. Para tal esta pesquisa foi dividida em dois estudos. O primeiro teve como objetivo investigar e descrever o conhecimento de profissionais de Educação Infantil sobre o TEA, o contato destes com este transtorno ao longo de sua carreira na educação, suas decisões ao identificar crianças com sinais de TEA, os encaminhamentos caso tenha como aluno com este diagnóstico e, sua opinião sobre a importância do diagnóstico precoce para a educação infantil. Participaram deste estudo 170 profissionais de 22 escolas da rede pública municipal de Educação Infantil de um município do interior de São Paulo. Os dados indicaram de... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Austitic Spectrum Disorder (ASD) can be defined as a genetic-based neurodevelopmental disorder, identifiable in early childhood, with persistent impairment in limit and impair the development of the individual (APA, 2014). This study assumes that knowing the characteristics of ASD allows the early identification of its indicators and. consequently, the referral of children to a specialized evaluation. In this perspective, this research aimed to investigate and describe the knowledge and experience of early childhood education professionals with children with ASD, and to elaborate, implement and evaluate the effectiveness of a program of these professionals for the early identification of indicators of the disorder. For this, research was divided in two studies. The first one had the objective to investigate and describe: the knowledge of Early Childhood professionals about ASD: The contact of these with this disorder throughout their career in education: Their decisions in identifying children with ASD indicators: The referrals if you have a student with this diagnosis and your opinion about the importance of early diagnossis for early childhood education. A total of 170 professionals from 22 shools of the municipal public education system participated in this study. The data indicated that professionals were not aware of the definition and characteristics of the disorder, despite the fact that most professionals affirmed that they had contact with people with ASD. It was also observed the unpreparedness and insecurity of these in relation to working with children with the disorder, which indicates the need for training on the ASD for the professionals of Early Childhood Education aiming at the early identification of the same. The second study aimed at developing, implementing and evaluating a training program for early childhood education professionals for the early identification of ASD... (Complete abstract click electronic access below) / Mestre