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The factors contributing to the severity of the neurodevelopmental disorders autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) are largely unknown. Previous studies have indicated immune abnormalities in these disorders, such as increased inflammation and altered immune cell numbers. We, in collaboration with the Province of Ontario Neurodevelopmental Disorder (POND) Network, analyzed markers of intestinal permeability and inflammation in children diagnosed with ASD or ADHD, as well as typically developing controls. Plasma from these participants was used to investigate levels of soluble inflammation, denoted by circulating acute phase proteins, as well as circulating levels of markers of intestinal epithelial damage and bacterial translocation. Peripheral blood mononuclear cells were isolated from these participants and used to construct an immunophenotype of ASD and ADHD, focusing on monocytes and monocyte activation and maturation. These data were then compared with scores of behaviour severity to identify associations between inflammation and behaviour in these disorders. We identified increased soluble inflammation in ASD, indicated by increased circulating C-reactive protein. We associated this inflammation with intestinal permeability, indicated by increased circulating LPS. Classical monocyte frequency was significantly lower in ASD and these monocytes displayed an altered migratory phenotype, indicated by a reduction in CCR2 expression. Furthermore, we have identified potential maladaptive monocyte responses to soluble inflammation in both ASD and ADHD, with altered monocyte phenotypes in response to inflammatory mediators compared to typically developing controls. Finally, we identified that changes in monocyte phenotype are associated with more severe behaviours in both ASD and ADHD. These findings imply that inflammation and immune abnormalities contribute to the severity of neurodevelopmental disorders. / Thesis / Master of Science (MSc)

The impact of birth order on language development has gained significant traction over the years, with contradictory evidence suggesting that lower birth order may hinder language development in typically-developing children (Nafissi and Vosoughi, 2015). However, results also suggest that when considering measures of social communication, second-born typically-developing children demonstrate a significant advantage (Kheirkhah and Cekaite, 2018). These findings have interesting ramifications when considering autistic children, as language impairments are characteristic of the disorder. The current study investigated the impact of birth order, in particular having an older, typically-developing sibling, on vocabulary and social language development in autistic youth. Participants included 1338 first-borns and 1049 second-borns (M age = 9.03 years, SD = 3.57; 86.4% male) with diagnoses of Autistic disorder, Aspergers, or PDD-NOS from the Simons Simplex Collection (Fischbach and Lord, 2010). Results indicated no significant differences in vocabulary or social language between first-borns and second-borns. Hierarchical linear regressions indicated no significant main effect of birth order; however, significant 2-way interactions with birth order x income and birth order x age predicted expressive vocabulary and inappropriate speech. Post-hoc simple slopes suggested that birth order may have a greater impact on language in younger autistic children, and lower-income families. This is the first work to date to investigate birth order and contextual factors on expressive language outcomes in autistic youth. / Doctor of Philosophy / Families provide an important context for important developmental milestones, such as language development (e.g., first words, firs phrases). Many parents and previous literature suggest that occasionally, older siblings can "speak on behalf" of their younger siblings, which reduces the number of opportunities second-born children have to practice important language skills. Previous literature in the field suggests that first-born siblings demonstrate stronger language skills when considering vocabulary, but that second-born siblings demonstrate stronger social language skills. The current dissertation evaluated these birth order findings in a clinical group of children and adolescents with Autism Spectrum Disorder (ASD), as language differences are key features of the disorder. Using a large, representative data set from the Simon Simplex Collection, nearly 3,000 youth with ASD were evaluated on vocabulary and social language skills, grouped by birth order status. Group comparisons suggested that there were no significant differences between first-borns and second-borns in vocabulary and language. When evaluating what factors predicted vocabulary and language, birth order was also not significant. However, some interaction effects emerged between birth order and income, suggesting that in lower-income families, birth order may make a meaningful difference in vocabulary and social language. This is the first work to evaluate the role of siblings on language in ASD, and has important implications for interventions, especially for lower-income families impacted by ASD.

The broad autism phenotype (BAP) has been defined both behaviorally and biologically. There has been little research on the association of the BAP, behaviorally defined, with neural or cognitive biomarkers typically associated with Autism Spectrum Disorder (ASD). People diagnosed with ASD tend to show reduced gaze fixation toward the eye region, but much less eye-tracking research has been done related to the BAP (Boraston & Blakemore, 2007). In this study, we sought to assess eye gaze patterns in people with the behaviorally defined BAP, as defined by a score of 30 or above on the Autism Spectrum Quotient (AQ; Baron-Cohen et al., 2001). It was hypothesized that the BAP group participants would exhibit longer average fixation duration to the eye region during an emotion recognition condition, relative to a free-viewing condition, whereas the comparison group participants (defined as an AQ score of 24 and below) would not show a difference in fixation duration to the eye region between conditions. Nine hundred and thirty-nine undergraduates completed an online survey, and 45 of these students (15 BAP group and 30 comparison group) participated in the eye-tracking session, where they viewed a series of human faces, each presented twice within a condition. Results revealed a significant negative relationship between social anxiety and eye region fixation duration in the free-viewing condition, for both presentations of faces. Contrary to expectation, BAP predicted longer eye region fixation duration in the free-viewing condition, for the second presentation of faces. Possible explanations for these surprising findings are discussed. / Master of Science

Emerging adults who have Autism Spectrum Disorder (ASD) often encounter difficulties within the university setting. Despite an increase in the number of students with ASD enrolled in postsecondary educational institutions, there are few reports on the social, academic, and/or other needs of college students with ASD. The purpose of this study was to assess the perspectives of parents of emerging adults with ASD and ADHD, in order to inform efforts to address the poor postsecondary outcomes of students with ASD. Survey data were collected from parents who had a son or daughter in one of three educational placement groups (parents of high school students, parents of postsecondary students, and parents of individuals aged 18-25 not enrolled in education) among two disorders; ASD and ADHD. Participants were recruited nationally to participate in an online survey. Parents of emerging adults with ASD identified social interactions and daily living as primary difficulties for their son or daughter with ASD. Significant differences emerged with respect to difficulties among emerging adults with ADHD, who identified difficulties related to executive functioning and attention. Social interaction training was an identified needed service by parents of emerging adults with ASD. Additionally, independent living training was a common core service requested by parents of individuals with ASD and parents of individuals with ADHD. Results suggest that the postsecondary profile of parent-reported difficulties and needed services remains distinct for the diagnostic groups ASD and ADHD. These difficulties should be considered within the context of intervention for postsecondary students with ASD and ADHD. / Master of Science

The ‘Structured Days Hypothesis’ suggests during less-structured periods, such as summer months or weekend days, children’s physical activity (PA) is lower and thus, may be detrimental to health. Exploring this hypothesis in children with autism spectrum disorder (ASD) is important, given they are less active and tend to prefer structure and routine compared to neurotypical peers. Weekend days are similar to summer days since both have reduced structure in comparison to the consistent weekday routine. The purpose of this review was to examine differences in PA levels of children with ASD during weekend days versus weekdays. Three databases (PubMed, APA PsycInfo, and ERIC) found 604 studies for screening. Seven studies met inclusion criteria (e.g., children 5-13 years, ASD diagnosis, weekend day and weekday PA outcomes). Three of the seven studies reported PA was greater on weekdays, two reported that PA was greater on weekend days, and two reported no differences. Findings provide researchers with insight into potential differences in PA of children with ASD during weekdays versus weekend days. Further studies are needed that purposefully measure PA during different environments to help inform PA interventions targeting children with ASD.

Title: Specifics of motor development in children with autism spectrum disorder Objectives: The aim of this thesis is to summarize the accessible literary sources about possibilities of early diagnostic of autism spectrum disorders, characteristic features of motor development and presence of movement and other abnormalities during early development in children who were later diagnosed with some disorder of autism spectrum. Methods: The study is divided into two main parts. In the first part, general information about autism spectrum disorders is presented. The ethiopatogenesis, characteristic features and different types of autism spectrum disorders are described. The second, descriptively analitical part, contains a brief description and resume of many studies, which deal with early identification of autism spectrum disorder, with examination of features of autism spectrum disorder in early development and motor abnormalities in individuals with autism spectrum disorder or high risk infants. Results: The results of this study indicate, that there are differences in social behaviour, motor development and specific autistic features already in the early development of children later diagnosed with autism spectrum disorder. Among motor abnormalities in early development in this children there are...

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