No description available.

No description available.

Autism spectrum disorder (ASD) encompasses a broad range of neurodevelopmental disorders, with two core symptoms: deficits in social communication, and restrictive interests and repetitive behaviors. Genetics is thought to play a large role in ASD and currently there are hundreds of associated genes. We first studied the thousand and one amino acid kinase gene (TAOK2), which plays an important role in neurodevelopment. We found that loss of TAOK2 causes deficits in neuron development and activity, leading to morphological changes in various mouse brain regions and ASD-related behaviors. We studied the impact of de novo mutations identified in TAOK2, which caused aberrant neuron dendritic arborization and formation of synapses. To elucidate how TAOK2 regulates neuron development we used a proximity-labeling proteomics technique (BioID) to identify its protein-protein interaction (PPI) network. We applied this same methodology to a total of 41 ASD-risk genes and observed multiple convergent biological processes, including the less-studied mitochondrial and metabolic pathways. ASD-risk genes, including TAOK2, associated with mitochondrial proteins were found to have altered cellular respiration. The shared ASD-risk gene PPI network enriched for other ASD-risk genes and was used to group genes based on their shared PPI networks. These gene groups showed correlation between the clinical behavior scores of individuals that had mutations within the distinct gene groups. Lastly, we identified changes in the PPI networks of multiple ASD-risk genes through BioID, which we validated with various functional assays. In summary, we developed a proximity-labeling proteomics method that identified multiple convergent biological pathways associated with ASD. Studying the function of TAOK2 revealed multiple disease-relevant pathologies associated with the disorder, however proximity labeling has the potential to categorize multiple ASD-risk genes and elucidate their shared signaling pathways, which together, can advance the development of robust treatments for ASD. / Thesis / Doctor of Philosophy (PhD) / Autism spectrum disorder (ASD) is a group of brain disorders that affect more than 1% of children. Genetic variants are thought to cause ASD pathology, however there are currently hundreds of genes that have not been studied. We studied how disruption of one of those genes, TAOK2, alters brain development in mice and identified TAOK2 variants in multiple children with ASD. We then used BioID to find the shared disease-related mechanisms between multiple ASD-risk genes, and found that mitochondrial function and activity were connected to many of these genes. We showed that BioID can be used to study the effect of mutations in multiple ASD-risk genes simultaneously. Last, we could group children with ASD with similar behavior test scores based on the shared mechanisms of ASD-risk genes. Together our findings could be used to advance the development of robust treatments or new diagnostic tools for ASD.

Thesis (M.S.) PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you. / Children with ASD suffer from language deficits that are in part due to impaired social abilities. In the current study, we test a non-social and noninteractive method for teaching word meanings. If successful, this technique will expand the ways we teach early vocabulary that would shape intervention and improve the quality of life and the future prospects of children with ASD. First, the participants (ages 26.09 - 47.37) listen to a series of transitive or intransitive sentences while watching an unrelated silent animation. These sentence types carry different meanings; transitive verbs describe causative actions, and intransitive verbs describe synchronous actions. Then they are asked to map the verb to meaning by finding the relevant action out of two candidate scenes. We analyze the children’s direction of gaze. The results revealed that children with ASD in this sample who heard transitive sentences in maximally non-social and non-interactive contexts did not show a significant preference for the causative scene in either test condition. Additional data will reveal whether children with ASD can learn from non-social presentation of novel words if given multiple exposures to the test scenes. This work will provide insight into the mechanisms underlying word learning in children with ASD and, if successful, provide the foundation for research into a new kind of non-social intervention that capitalizes on these children’s strengths. / 2999-01-01

Applied behavioral analysis (ABA) is an evidenced-based treatment used in the treatment of autism spectrum disorder (ASD) symptomology. This treatment modality addresses difficulties individuals with ASD experience, including deficits in social communication, and repetitive and/or restricted behaviors. A variable pattern of developmental milestone acquisition, particularly language, is an early indicator of ASD. Perhaps due to the variability in presentation, the mean age at diagnosis is 4-5 years old despite feasibility of diagnosis as early as 2 years of age. Tracking a child's development is essential for early identification of ASD, with age at diagnosis significantly impacting intervention outcomes in this population. Ideally, individuals with suspected ASD are comprehensively assessed and engaged in intensive early intervention with personalized goals targeting multiple domains of functioning, including cognitive abilities, adaptive functioning, and/or language functioning. Unfortunately, significant barriers (e.g., too few qualified professionals, inaccessible treatment centers, long waitlists) have been identified that preclude access to care for many individuals in need of evaluation and/or treatment. Given the typical delays in identification and the frequent barriers to access, assuring families that the care of their child is of paramount importance and will be met with high quality, evidence-based practices is appropriate. The purpose of the multi-site study was to assess treatment-as-usual across autism intervention centers, drawing archival data from Autism Comprehensive Educational Services (ACES). Results indicated no significant differences in standardized scores of adaptive functioning but significant differences in criterion referenced skills across three time points. Future directions are discussed.

Thesis (Ed.D.)--Boston University / Through written survey and recorded interviews a snapshot in time was taken on how theorists of five promising approaches- Applied Behavioral Analysis, TEACCH, Daily Life Therapy, Miller Method, and DIR- think about children on the autism spectrum. Some of the findings include agreement on the need for a better definition of autism, the need for treatment-based research for developing and maintaining best practice, that the diversity of needs of people on the autism spectrum requires a wide range of approaches, and a general sense that people with autism have many valued strengths to contribute to society. Other findings include extensive use of non standardized assessments along with judicious employment of standardized instruments. Finally, all the theorists - some of home have spent more than 4 decades helping children with autism - all feel that the work they have done can be useful to youth with other challenges as well. / 2999-01-01

Despite the rising prevalence of autism spectrum disorders (ASD), interventions for the adult population, most of whom do not achieve independent living, are limited (Seltzer, Shattuck, Abbeduto, and Greenberg, 2004). Additionally, many individuals with ASD experience impaired emotion regulation (ER), which is thought to contribute to higher rates of psychiatric comorbidities among adults with ASD as well as indirect effects upon adaptive functioning, interpersonal relationships, and vocational status ( Mazefsky et al., 2013; Samson, Huber, and Gross, 2012). The primary purpose of the current study was to investigate the initial feasibility and efficacy of an adapted mindfulness-based individual therapy for adults with ASD to target ER difficulties, and evaluate ER as a potential change process. Initial feasibility of mindfulness-based approaches among adults with ASD was supported by acceptable treatment fidelity and participant satisfaction ratings. Efficacy of the intervention was partially supported; four of the participants demonstrated significant improvements in impulse control, access to ER strategies, and emotional acceptance, and two of the participants evidenced significant decreases in emotional symptom distress. Analysis of ER as a potential change process found significant improvement for four participants, but slopes demonstrated that improvement initiated before treatment, a confound for determination of change processes. Further research is recommended, including additional timepoints, a clinical cutoff-derived sample, and further understanding of the role of self-regulatory deficits for individuals with ASD. / Ph. D. / Despite the rising numbers of people with autism spectrum disorders (ASD), interventions for adults with ASD, most of whom do not achieve independent living, are limited (Seltzer, Shattuck, Abbeduto, & Greenberg, 2004). Many adults with ASD have impaired emotion regulation (ER), which is thought to contribute to higher rates of co-occurring diagnoses such as depression and anxiety disorders, and reduces overall quality of life (Mazefsky et al., 2013; Samson, Huber, & Gross, 2012). The primary purpose of the current study was to investigate the practicality and usefulness of an adapted mindfulness-based individual therapy for adults with ASD to target these difficulties in ER, and to judge whether ER is a potential change process in the improvement of overall functioning. Nine individuals with ASD who were between the ages of 18-25 participated in the study. After their diagnosis of ASD was confirmed, they were assigned to either 3- or 4-week baseline period in order to assess their functioning before the treatment, and then began the 6 weekly therapy sessions on mindfulness. Initial practicality to conduct mindfulness-based approaches among adults with ASD was supported by acceptable treatment fidelity (adherence) and participant satisfaction ratings. Helpfulness of the intervention was partially supported; four of the participants saw significant improvements in control of emotional impulses, learned to use more ER strategies, and accepted their emotions more often, and two of the participants showed significant decreases in emotional distress. Study of ER as a potential change process found that four participants had significant improvements in their overall ER skills, but graphs showed that improvement began before the treatment, leading to questions about whether the intervention was the only reason for improvement. Further research is recommended.

The comorbidity of anxiety disorders and autism spectrum disorder (ASD) is well-established. Although research on the comorbidity of anxiety disorders in adults with ASD is limited, preliminary studies suggest rates of comorbidity comparable to those found in children and adolescents. Little is known about the manifestation of anxiety symptoms in adults with ASD or the potential for these symptoms to impact quality of life in this population. The current study aimed to examine the role of anxiety symptoms in quality of life among young adults with ASD. We collected online survey data from a large sample (N = 224) of parents of young adults with ASD and a subsample of adults with ASD. Parent- and self-report data suggested a substantial proportion of adults with ASD exceeded clinical cutoffs for anxiety symptoms. Anxiety moderated the relationship between ASD severity and the social relations domain of quality of life. Anxiety symptoms did not, however, significantly moderate the effect on the psychological domain. Exploratory analyses also demonstrated significant indirect effects of ASD severity on social and psychological quality of life through anxiety symptoms. Results provide preliminary evidence that anxiety symptoms contribute to quality of life in adults with ASD independently of core ASD symptomatology. Future research should aim to further characterize anxiety symptoms among adults with ASD, as well as evaluate the impact of anxiety symptoms on quality of life and overall outcome through the use of prospective longitudinal studies. / Master of Science / The comorbidity of anxiety disorders and autism spectrum disorder (ASD) is wellestablished. Although research on the comorbidity of anxiety disorders in adults with ASD is limited, preliminary studies suggest rates of comorbidity comparable to those found in children and adolescents. Little is known about the manifestation of anxiety symptoms in adults with ASD or the potential for these symptoms to impact quality of life in this population. The current study aimed to examine the role of anxiety symptoms in quality of life among young adults with ASD. We collected online survey data from a large sample (<i>N</i> = 224) of parents of young adults with ASD and a subsample of adults with ASD. Parent- and self-report data suggested a substantial proportion of adults with ASD have clinically significant levels of anxiety. Anxiety symptoms contributed to poor quality of life above and beyond ASD symptoms alone. Exploratory analyses also demonstrated significant effects of ASD severity on quality of life through the path of anxiety symptoms. Results provide initial evidence that anxiety symptoms contribute to quality of life in adults with ASD independently of core ASD symptoms. Future research should aim to further characterize anxiety symptoms among adults with ASD, as well as evaluate the impact of anxiety symptoms on quality of life and overall outcome through the use of prospective longitudinal studies.

Individuals with autism spectrum disorder (ASD) are at an increased risk to be victims of bullying due to the core characteristics of the disorder. Prior research has focused on understanding bullying from the perspectives of individuals with ASD, parents, and practitioners through interviews and questionnaires. However, limited evidence exists using interventions to teach individuals with ASD about how to identify and respond to bullying. This study employed Kidpower® bullying narratives to teach individuals with ASD how to identify and respond to various bullying scenarios. Kidpower was selected to provide practitioners with a pre-established curriculum to utilize, rather than creating materials for each student. A multiple probe design across three participants was utilized to (a) teach individuals with ASD how to identify and respond to bullying drawings on Kidpower narratives, and (b) add an experimental study to the limited literature base pertaining to strategies for teaching about bullying to individuals with ASD. A fourth participant was also included as a case study. Progress for all participants was measured using the percentage of correct responses to 10 questions. Three out of four participants reached the mastery criterion of 90% over two consecutive sessions. Sessions for the fourth participant concluded after seven intervention sessions due to the COVID-19 pandemic. Many modifications were made to the original study design including changing the wording of the dependent variable and using more simple stories. No modifications were made to the actual stories. This study indicates the Kidpower narratives are helpful in teaching individuals with ASD who also meet certain criteria based on verbal comprehension. However, additional information is necessary in order to assess understanding of bullying.

Motor deficits in children who are diagnosed with Autism Spectrum Disorder (ASD) have started to become recognized as an area of concern. The purpose of this study was to examine practices of board-certified music therapists who address motor goals of children with ASD. A total of 168 current board certified music therapists completed an 18-item online survey regarding music therapy practices with children who have ASD, particularly the frequency with which they address motor goals and specific goals and interventions. Respondents reported addressing motor goals with children who have ASD more frequently than suggested by previous research. Motor goals most commonly addressed include imitation, upper limb coordination, hand/eye coordination, compliance, and praxis skills. The most common interventions used to address motor goals were instrument play, movement activities, dancing, using manipulatives, and task-oriented music games. Using information provided from the study, music therapists will be better equipped in helping children with ASD who have motor deficits by providing a list of commonly used interventions and which specific motor goals they are used most commonly with.