One of the defining characteristics of Autism Spectrum Disorder (ASD) is repetitive, rigid, or stereotyped patterns of behavior. A proposed approach to treating such patterns is to provide reinforcement for response variability. Though research demonstrates that the variability of responses can be influenced by contingencies of reinforcement, no studies have examined the effects of placing contingencies on different units of behavior. The purpose of this study was to examine effects of two modified percentile schedules on variety of completed drawings and individual lines drawn by students with ASD who had been referred for engaging in rigid patterns of behavior. For all three participants that completed drawing sessions, results indicated that drawing variability increased the most when reinforcement was contingent on the variability of the completed drawing, as opposed to a random ratio schedule of reinforcement or reinforcement being contingent on individual lines being varied.

The purpose of this study was to evaluate the process and outcomes of using the Teaching Tools for Young Children with Challenging Behavior (TTYC) with two kindergarten classroom teachers and two high functioning children with autism spectrum disorders engaging in moderate problem behavior during daily classroom routines. The focus was to evaluate the extent to which the kindergarten teachers could adequately use the TTYC toolkit with minimal behavioral consultation in the assessment and intervention process and to examine its impact on student behavior. A multiple baseline design across routines was used for each child to evaluate the child outcomes. The results indicated that the teachers successfully used the TTYC toolkit to design and implement routine-based intervention plans with fidelity, and their implementation of the intervention plan led to increased replacement behavior and decreased problem behavior across routines for both children. Improved levels of behaviors were maintained at 2-week follow up for one child.

Infants 5-34 weeks of age were observed in their homes playing with their mothers as part of a longitudinal study. Two mother-infant dyads were observed once per week for twelve weeks, during a ten-minute play session. The purpose of the observation system is to describe contingencies leading to the development of attention-seeking behaviors in typically developing infants. Observations were coded using a type-based format (person engagement, object engagement, supported joint engagement, coordinated joint engagement, and unengaged). Child eye gaze, reaching, and grabbing were coded as well as all child and adult vocalizations. It is suggested that the data from the observation system will help inform and assess the effectiveness of infant and toddler social interventions in autism spectrum disorders and advance our understanding of attention seeking behaviors.

This qualitative research study explored areas of similarity and contrast between a music therapy student's interpretations of selected audiovisual excerpts from music therapy sessions with a child with Autistic Spectrum Disorder (ASD), and his parent's interpretations of the same. A further feature of the study was investigating how these interpretations could inform the collaborative creation of a music activity for use in the home environment. Eight one-on-one music therapy sessions were conducted with an eight year-old boy with ASD at Alpha School in the Western Cape. The sessions were video recorded. Once the music therapy process was complete, four primary excerpts and five secondary excerpts were selected. Interpretations of the four primary excerpts were written by the music therapy student. A semi-structured interview consisting of two parts was then conducted with the child's parent. Part one involved eliciting the parent's interpretations of the four primary excerpts. Part two involved the viewing of the five secondary excerpts as part of a discussion between the music therapy student and parent, leading to the collaborative creation of a music activity for the home environment. The interpretations of the music therapy student and parent were matched with the music therapy student's interpretations for the purposes of qualitative content analysis and comparative analysis. Codes were derived for the interpretations, and then grouped into sub-categories and categories. Two overarching themes were then drawn from the data: operation of the music therapy student's contextual lens; and operation of the parent's lens. Within these two themes, different sub-themes were present: music therapy student’s reflexivity; focus on developing relationship; focus on clinical musical features; valuing offerings as musical; parent's pride in her child; noticing musical interactions; and focusing on successful interactions. These themes then implicitly informed the collaborative creation of a music activity for the home context. / Dissertation (MMus)--University of Pretoria, 2017. / Music / MMus / Unrestricted

Os transtornos do espectro autista (TEA) são distúrbios neuropsiquiátricos bastante comuns, graves, e que propiciam grande impacto social e financeiro. A identificação de vias moleculares e processos celulares alterados que são compartilhados pelos pacientes, mesmo que estes apresentem causas etiológicas distintas, pode contribuir de forma significativa para o entendimento de sua patofisiologia desses transtornos. Ainda, a identificação destas vias pode propiciar o desenvolvimento de abordagens terapêuticas mais eficientes, uma vez que o uso de medicamentos nos TEA ainda é inadequado, envolvendo baixa melhora funcional e diversos efeitos colaterais, como o ganho excessivo de peso e anormalidades metabólicas associadas. Neste trabalho, selecionamos como uma primeira abordagem o estudo da via de sinalização PI3K-mTOR em pacientes com TEA não-sindrômico, via esta envolvida com diversos aspectos do desenvolvimento e funcionamento neuronal, assim como com a patofisiologia de síndromes monogênicas que apresentam alta prevalência de TEA em seu quadro clínico. Foram utilizadas como modelo experimental in vitro células-tronco mesenquimais provenientes de polpa de dente decíduo (SHEDs) de pacientes e indivíduos controles. Os resultados aqui obtidos sugerem a importância da desregulação da via PI3K/mTOR na patofisiologia de uma parcela importante dos casos de TEA não-sindrômico. Ainda, observamos que as células dos pacientes com alterações nessa via de sinalização apresentam maior capacidade proliferativa, e que a modulação deste fenótipo alterado por meio do uso concomitante de inibidores de PI3K e mTOR nas células de um destes pacientes sugere esta via como um alvo promissor para o desenvolvimento de novas abordagens terapêuticas para estes pacientes. Em seguida, na tentativa de desvendar os mecanismos subjacentes aos efeitos metabólicos adversos associados com o uso de antipsicóticos prescritos para o tratamento de pacientes com TEA, investigamos os efeitos destes psicofármacos sobre a biologia do tecido adiposo humano. Foram utilizadas como modelos in vitro células-tronco (ADSCs) e adipócitos maduros derivados de tecido adiposo humano de indivíduos controles. Os resultados obtidos sugerem que a ação direta dos antipsicóticos com alta propensão ao ganho de peso (como a olanzapina e a clozapina) sobre a proliferação, diferenciação, e o metabolismo do tecido adiposo humano parece não constituir um mecanismo importante associado ao ganho de peso apresentado pelos pacientes, e que a ação desses medicamentos sobre os sistemas centrais que regulam o peso e o metabolismo deve ser o mecanismo principal levando aos efeitos metabólicos adversos. Juntos, os resultados gerados neste trabalho podem, de certa forma, contribuir para da farmacoterapia dos TEA / Autism spectrum disorders (ASD) are common neuropsypchiatric disorders, which has serious social and economic impacts. Identification of common molecular and cellular processes altered in patients, despite the underlying genetic heterogeneity, can contribute significantly to our understanding of the disease pathophysiology and can help to develop more effective treatments, since available pharmacotherapy for ASD is inefficient and frequently associated with adverse side effects, such as weight gain and metabolic disturbances. Here, we used patient-derived Stem cells from Human Exfoliated Deciduous teeth (SHEDs) as an intro model system to investigate whether non-syndromic ASD patients show altered regulation of PI3K/mTOR signaling pathway, which is involved in multiple aspects of neuronal development and physiology, and in the pathogenesis of monogenic syndromes that share features with ASD. Our results suggest that dysregulation of PI3K/mTOR-linked networks play an important role in the pathogenesis of a subgroup of non-syndromic ASD. In addition, we found enhanced proliferative capacity in cells with altered PI3K/mTOR activity, which was rescued in one of these patients through combined pharmacological inhibition of both PI3K and mTOR kinase activity, suggesting that PI3K-mTOR signaling is a promising target for the development of new therapeutic approaches for these individuals. Next, in an attempt to better understand the mechanisms underlying the metabolic side effects of the antipsychotics prescribed for ASD treatment, we investigated the effects of some of these drugs on the biology of human adipose tissue using as in vitro model systems human adipose-derived stem cells (ADSCs) and mature adipocytes. Our results suggest that a direct and potent effect of antipsychotics with high weight gain liability (such as clozapine and olanzapine) on cell proliferation, differentiation, and metabolism of human adipose tissue is not an important mechanism by which these drugs induce metabolic disturbances. Consequently, our results suggest that these side effects may mainly reflect the action of these drugs on central pathways involved in weight control and metabolism. Together, our results can, to some extent, contribute to improving pharmacotherapy of ASD

Submitted by Nadir Basilio (nadirsb@uninove.br) on 2016-05-17T21:15:09Z No. of bitstreams: 1 Juciara da Costa Silva.pdf: 1474997 bytes, checksum: 68c03923ff3474f155a9c981efd3d3ab (MD5) / Made available in DSpace on 2016-05-17T21:15:09Z (GMT). No. of bitstreams: 1 Juciara da Costa Silva.pdf: 1474997 bytes, checksum: 68c03923ff3474f155a9c981efd3d3ab (MD5) Previous issue date: 2015-03-05 / Maternal thyroid dysfunction and its most common condition, gestational hypothyroidism, may facilitate fetal neurodevelopmental disarrangements. Disorders in neurodevelopment arising from subclinical and often not-detectable maternal thyroid dysfunction share similarities with some of the cognitive and behavior alterations manifested in autism spectrum disorders (ASD). In particular, fetal deficits in cortical migration, neuronal fate and maturation impair fine aspects of cognitive function and social behavior in these social and clinical conditions. To date however, there are very few studies, which address in detail the predominant deficits in communication and sociability in late-adolescence and young adult individuals regarding their sex differences related to subclinical maternal hypothyroidism during pregnancy. Using an animal model of mild maternal hypothyroidism, we investigated social behaviors of the offspring after puberty in both male and female mice and looked for changes in their anxiety and aggression levels and vocalization as well as their sex dependence. Our study showed an increase in induced anxiety paralleled by relatively reduced vocalization in male offspring subjected to mild hypothyroidism in pregnant female mice. These experimental findings not only open a neurodevelopmental window to investigate the molecular aspects of these behavioral abnormalities but also and may foster educational, psychological and medical advances in late-stage child neurodevelopment among the ASD individuals / A disfunção tireoidiana materna com destaque no hipotireoidismo causa representativos danos neurológicos para o feto que em muitos aspectos cognitivos se assemelham às alterações neurobiológicas das doenças do espectro autista, como exemplo: alterações de migração cortical, comprometimento de especialização neuronal e modificações nas funções cognitivas. Há uma escassez de estudos para melhor esclarecer e caracterizar as alterações de comportamento na prole pós-puberal, cujo impacto no neurodesenvolvimento intra-útero ocorrera facilitando os prejuízos tardios de sociabilidade animal. Utilizando um modelo murino de hipotireoidismo materno (tratamento com metimazol), estudamos as alterações em comportamentos sociais da prole após o período puberal, a fim de entendermos os variados aspectos de prováveis alterações cognitivas e motivacionais em machos versus em fêmeas. Realizamos o estudo com foco em comportamentos vislumbrando agressividade ofensiva e defensiva, vocalização social, e autopreservação (i.e.; medo; ansiedade) bem como, adaptações neurovegetativas (i.e.; regulação térmica). Os dados mostraram um acometimento da prole masculina proveniente de mães tratadas com metimazol 30 dias antes da gestação ocorrer. Esse projeto correlacionou aspectos etológicos com um grande tema da esfera clínica em humanos no que tange doenças do neurodesenvolvimento e desarranjos sociais mais brandos, porém abrangentes e prevalentes e suas repercussões comportamentais na vida pós-puberal e adulta.

Autism Spectrum Disorder (ASD) is a diverse disorder, and the heterogenous range of possible presentations hinders our understanding of its aetiology. Recently there has been a surge of genome wide association studies for ASD, while historically psychological theories were relied on to explain the emergence of ASD. These fields continue to provide insights into ASD, but they tend to operate in parallel – genetic studies often lack comprehensive psychological phenotyping and theoretical backing, and psychological studies tend to lack genetic explanations. I propose that moving forward, genotype-phenotype studies should have a strong foundation in both fields and should focus on genes and theories with realworld implications for ASD diagnostics and/or interventions. This approach can be supported by focusing on established, well supported psychological theories, and selected ASD candidate genes that could be implicated in these theories, and ideally the genetic mechanism implicated should be one that can be targeted by existing medications. I therefore selected two prominent psychological theories, the Social Motivation Theory for ASD (Panksepp, 1979) and the ToM Theory for ASD (Baron-Cohen et al., 1985), and selected an ASD candidate gene that was likely implicated in each of these theories, namely the mu-opioid receptor gene (OPRM1) and the serotonin transporter promoter length polymorphism (5-HTTLPR) respectively. For the first study of this protocol, I assessed the possible relationships between social motivation, OPRM1, and the ASD phenotype. For the second study, I assessed possible relationships between ToM deficits, 5-HTTLPR, and the ASD phenotype. These two studies shared a sample of 153 male children 4-16 years old; 51 boys per group (i.e. non-verbal ASD; verbal ASD; neurotypical). All ASD children completed ADOS2 assessment for ASD phenotyping. For the Social Motivation Study, attachment was used as a proxy to assess level of social motivation in all participants, and 76 of the 102 children with ASD provided DNA for OPRM1 genotyping. Comparisons across all three groups showed that the ASD samples had significantly lower social motivation than the neurotypical sample, with the non-verbal ASD group displaying the most severely reduced level of social motivation. Reduced social motivation was associated with ASD-related deficits in the non-verbal ASD sample but not the verbal ASD sample. Finally, I was unable to statistically assess the role of OPRM1 as hypothesized, due to an unprecedentedly high rate of the OPRM1 G allele, which indicated atypical mu-opioid processes. This clearly implicated OPRM1 in ASD and is the first study to show this so convincingly. Overall, this study's findings led me to suggest that Panksepp's (1979) theory could be updated to include a threshold effect such that more severely reduced social motivation in ASD is associated with little-to-no language acquisition, while those with less severely reduced social motivation are able to develop language and this protects against associations between social motivation and ASD-related deficits in childhood. For the Theory of Mind Study, the verbal ASD sample and neurotypical sample completed a developmental ToM Battery (i.e. University of Cape Town Theory of Mind Battery) and WASI assessment to establish verbal intelligence quotient (VIQ) scores, and 70 of the children with ASD were successfully genotyped for 5-HTTLPR. This study found that verbal male children with ASD tended to be one developmental stage behind age-matched neurotypical peers on ToM tasks. ToM deficits were associated with greater impairment in overall ASD severity and in symptoms from the social communication and interaction domain. For the non-verbal ASD sample, the 5-HTTLPR short allele, which is implicated in atypical serotonergic transmission, was associated with greater impairment overall and in the restricted and repetitive behaviours and interests symptom domain. No associations between 5-HTTLPR and ToM, or with ASD-related symptoms, was found for the verbal ASD group. This again suggested that language acquisition is an important consideration in genotypephenotype studies in male children with ASD.

Systematic review is a type of review that identifies, assesses, and combines all the published empirical evidence on a specific topic by using explicit, systematic methods. This type of reviews often includes a meta-analysis, a statistical tool used to combine the collected data into a quantitative summary estimate. Guidance documents such as the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) were developed to improve the reporting of systematic reviews of randomized controlled trials. Systematic reviews are commonly used in the field of healthcare research and are increasingly being employed in the field of environmental epidemiology. Environmental epidemiology studies examine exposures in populations and their associations with health outcomes. This field contains several unique considerations that require a careful and critical assessment to ensure the validity of results and to make the data or information more useful for the readers. However, to our knowledge, there is currently no guidance document for conducting systematic reviews that comprehensively addresses the specific issues in this field. Therefore, the objectives of this proposal are twofold: (1) to conduct a systematic review of the currently published epidemiology systematic reviews on a specific topic (mercury exposure and children autism spectrum disorder) to identify analytical issues encountered, and (2) use the experience and other potential solution identified in the literature to develop a guidance or recommendation document for conducting systematic reviews of environmental epidemiology studies. Akin to reporting guidelines for randomized controlled trials, a reporting guideline for environmental epidemiology is anticipated to increase the clarity and transparency of publications and enhance the usefulness of systematic reviews for knowledge synthesis.

Dès les descriptions princeps des Troubles du Spectre de l’Autisme (TSA), l’accent a été mis sur les perturbations de l’identité subjective qu’il est possible d’étudier grâce à la conceptualisation de Conway qui fait interagir le self et la mémoire autobiographique. En nous basant sur ce modèle, nous avons exploré les spécificités du self dans les TSA Sans Déficience Intellectuelle (TSASDI) à travers l’étude de ses dimensions subjectives, conceptuelles et structurelles. Nos résultats retrouvent une atteinte du self au niveau structurel mais pas conceptuel ou subjectif. De plus, nous avons montré une atteinte de la fonction sociale de la mémoire autobiographique et que les images de soi sociales appartenant au self étaient associées à des souvenirs qualitativement différents. Nos résultats nuancent l’altération de la composante épisodique de la mémoire autobiographique et invitent à préciser l’influence des relations sociales sur le self et la mémoire autobiographique dans ces troubles. / Since first descriptions of Autism, disorders of self have been seen as key symptoms. The Self-Memory System put forward by Conway describes the reciprocal relationships between the self and autobiographical memory. This model was the theoretical background of our investigations of the specificities of the self in adults with Autism Spectrum Disorder without Intellectual Deficiency. We addressed three issues: structural aspects, concepts and subjective characteristics of the self. Our results showed an impairment of structural aspects of self while concepts and subjective characteristics were spared. Indeed, we found that the social function of autobiographical memory was altered and that social self-images belonging to self-concepts were related to qualitatively different memories. Our results challenge the episodic autobiographical memory deficit classically reported and encourage new researches to explore the impact of social relationships on the self and autobiographical memory.

Autism spectrum disorder (ASD) is associated with functional abnormalities of the anterior cingulate cortex (ACC), a brain area that mediates social behavior. Given evidence of a role of inflammation in ASD, markers of pro-inflammatory and anti-inflammatory microglia were studied using postmortem ACC tissues from ASD and age-matched typically developed control donors. Gene expression levels of pro-inflammatory (CD68, HLA-DRA, IL1B, NOS2, PTGS2) and anti-inflammatory (ARG1, IGF1, MRC1, PPARG) microglial genes were measured using quantitative real-time PCR. Additionally, brain sections were immunohistochemically stained for a microglial marker. Expression levels of IGF1 were modestly higher, while the expression of MRC1 was modestly lower in ASD donors when compared to control donors. No other differences in gene expression levels between the two groups of donors were observed. Statistical significance for changes in expression levels IGF1 and MRC1 did not survive correction for multiple comparisons. Further research on anti-inflammatory microglial involvement in ASD is warranted.