The aim of this proposed study is to explore whether participation in a three day intervention involving horseback riding in nature– a program specifically designed for autistic children and their families called “Horse Boy Camps” – leads to improved outcomes for participants. It is hypothesized that children will demonstrate significant increases in language and communication skills after camp participation, as well as enhanced social, cognitive and sensory functioning. It is also hypothesized that attendance at a Horse Boy Camp will have an impact on the parents and siblings of the child with autism. Specifically, it is anticipated that camp participation will significantly decrease the anxiety, stress, depression and social isolation experienced by parents. It will also result in significant improvements in the relationship between the autistic and their siblings as well as family functioning in general. Participants will include 20 families attending a three-day Horse Boy Camp. There will be one autistic child per family who attends the camp, and at least one parent. The proposed study will help determine if Horse Boy Camps appear to be a promising intervention for children with autism and their families. / text

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

published_or_final_version / Paediatrics and Adolescent Medicine / Master / Master of Medical Sciences

published_or_final_version / Public Health / Master / Master of Public Health

Autism is a life-long neurodevelopmental condition. Autistic individuals have difficulties in communicative and social ability, and repetitive and stereotypic behavior. It has proposed that these symptoms are caused by underconnectivity in the autistic brain. Functional imaging studies have reported functional underconnectivity in autism. In this thesis, the structural connectivity of the autistic brain was studied. White matter contains axon fibers, which connect different cortical and subcortical brain regions. To measure the structural connectivity, Diffusion tensor imaging (DTI) was applied. Since water diffusion in axons inside the white matter is directional, by measuring the magnitude and direction of water diffusion in white matter, the structural integrity of white matter fibers could be estimated. In this thesis, the background of autism as a genetic, neurological and behavioral condition is outlined. The methods needed to acquire and analyze DTI data are illustrated. A meta-analysis on abnormalities found in autistic brain using DTI was conducted and the most consistently reported regions with DTI differences in autism compared to typically developing controls are described. The results of the metaanalysis were localized to white matter tracts likely to be involved, and the possible associations between anatomy and autistic behavioral features are discussed. Finally, a DTI tractography study was conducted in a sample but clinically representative sample of patients with ASD and eighteen major white matter tracts were explored. Underconnectivity in several tracts was identified. It is hoped that the findings reported here will enhance our understanding of widespread underconnectivity in autism. / published_or_final_version / Psychiatry / Master / Master of Philosophy

While a stable diagnosis of Autism Spectrum Disorders can be made as early as 2 years of age, the diagnosis of mild ASD cases are usually not made until primary school age or much later; and yet it is these milder cases that can benefit the most from early intervention. The present study aimed at pushing the identification of mild ASD children earlier to preschool age. A review of current screening tools revealed that they were not effective in identifying milder ASD variants. One reason perhaps is that the existing tools rely primarily on parental reports. Note that young children with mild ASD often function adequately interacting with an adult who knows them well; they typically face more difficulty in free play with other children. Parents as a result may not be in a good position to detect milder ASD. The present study therefore took a very different approach from existing screening tools by developing a more objective scale based on observation by of peer interaction in preschools. Considering peer interaction deficits are central for ASD, and deficits of these milder individuals might be more obvious in a setting that tax their social skills. A screening tool based on peer interaction observation in preschool, namely the Structured Classroom Observation Scale (SCOS), was thus developed. Drawing on existing screening tools and experts input, 84 items were compiled and pilot tested. An initial psychometric study of the scale was conducted using a community sample, with 304 preschoolers aged 3 and 4, from four English-language international schools in Hong Kong. The initial 84-item version was trimmed substantially to result in a user-friendly 13-item observation scale with good psychometric properties. The final SCOS includes 3 items depicting self-regulation challenges and 10 items describing difficulties in peer interaction. The initial psychometric study using a community sample indicated substantial interrater reliability (u= .76) and acceptable test-retest reliability (ICC = .72). The average agreement for individual items was less satisfactory (T = .40). Using Latent Class Analysis, the present scale delineated the children into 4 groups: Typical, Shy, Behavioral and High Risk of ASD. A subsequent validity study (n = 186) comparing the SCOS with ADOS scores showed that the class membership of the children based on SCOS predicted their ADOS results, after controlling for age and gender. Children from the High Risk group were found to have significantly higher Calibrated ADOS Severity scores than the other 3 groups; and their mean ADOS scores (i.e., 8.18) were above the cutoff for ASD on the ADOS. A 9-month follow found more reports of parental concerns in the High Risk group with ADOS scores above the cutoff. Discriminant validity of the SCOS was demonstrated between the scale and Head Start Competence Scale (parent version). In contrast to the usual portrayal of active but odd stereotypical children with Asperger Syndrome, the High Risk group identified by the SCOS consisted of children with infrequent interfering behaviors. They were relatively passive but not necessarily odd during social interactions, which might perhaps explain why early identification was difficult. The current scale also identified another two groups of children (Shy group and Behavioral group), which will require longitudinal follow up to ascertain educational or intervention implications. / published_or_final_version / Clinical Psychology / Doctoral / Doctor of Psychology

Background: The Weak Central Coherence (WCC) account of autism spectrum disorder (ASD) proposes a weakness of global integrative processing (i.e. central coherence) resulting in a strength in local, detailed, focused processing in individuals with ASD. However, because of the mixed findings regarding weaknesses in global integrative processing, recent literature had neglected this part of the WCC theory. Mixed findings about global integrative deficits in ASD came about because WCC was operationalized differently in different studies. This research’s primary aim was to delineate the nature of integrative processing that is impaired in ASD more precisely. Integrative processes were demarcated into first order and second order processes. Individuals with ASD were hypothesized to have problems in second order integrative processing only, which refers to the apprehension of inter-elemental relations that exist external to the individual elements. The hypothesis was investigated in both the visual-perceptual domain (Study One) and the verbal-conceptual domain (Study Two). In the visual-perceptual domain, first order and second order integrative processing refer to global processing and gestalt processing respectively. In the verbal-conceptual domain, they refer to the apprehension of taxonomic relations and thematic relations respectively. With better delineation of the construct of integrative processing in WCC, Study Three pursued the secondary aims of this research: to use the clarified constructs to study whether WCC exists as a central mechanism, and to test its predictive value on ASD symptomatology. Methods: Twenty high functioning adolescents with ASD (HFA, aged 12 to 15) and 20 matched typically developing (TD) counterparts (aged 12 to 15) participated in the three studies of this research. In Study One, participants were administered a first order task with hierarchical compound stimuli that aimed to tap their global processing, and a second order task that aimed to tap their apprehension of gestalt principles (gestalt processing). In Study Two, participants were administered a lexical decision priming task with half of the prime-target pairs denoting a taxonomic relation (first order task), and half of the prime-target pairs denoting a thematic relation (second order task). In Study Three, correlation analyses were done among the second order task measures of the two domains as well as HFA symptomatology indexed by the Autism Quotient (AQ). Results: For Study One, there was a trend showing that participants with HFA performed worse than TD peers in a subtask that tapped one gestalt principle (the principle of similarity). Contrary to prediction, in the global processing task, HFA individuals exhibited a reliable local bias. For Study Two, HFA participants were found to be primed to a significantly lesser extent by a thematic prime while exhibiting intact taxonomic priming. In Study Three, cross domain associations of second order processing measures were not significant, which was against the notion of a central mechanism of WCC. The priming extent by a thematic prime and a measure of gestalt processing were found to associate negatively with ASD symptoms in the TD group. Conclusions: All in all, the present research had partial success in clarifying the nature of WCC as a weakness in second order integrative processing. Theoretical and practical significance as well as future research directions were discussed. / published_or_final_version / Educational Psychology / Doctoral / Doctor of Psychology

Valproic acid (VPA) is a broad-spectrum anticonvulsant and antiepileptic drug and widely used in many neurological conditions and psychiatric disorders as well as in cancer and HIV treatment. However, despite all its many benefits, VPA also has side effects. It is a strong fetal teratogen that can induce congenital malformation and neurodevelopmental problems. Case reports and population studies have revealed that prenatal exposure to VPA is associated with a higher risk of autism in postnatal life. Animal models also have confirmed that VPA can induce autistic-like features in rodents. Yet, there are some questions remaining unanswered by existing animal studies of prenatal VPA exposure. The embryotoxicity of a drug is not only determined by its own chemical, physiological or pharmacological properties, but also on the dose and the time in development that the exposure happens. The majority of studies investigating the behavioral, neuroanatomical and physiological impact of VPA in animals have examined early gestational exposure to relatively high doses that can cause significant malformation or loss of offspring. Thus, although there are behavioral alterations considered similar to autistic symptoms in humans, these are found in the offspring that have survived a very toxic insult, leading to problems of interpretation. Low dose exposure has not been widely studied, nor has the impact of VPA exposure late in gestation. Moreover, how the age and sex of offspring influences the phenotypic outcome has rarely been considered. Therefore, in the present series of studies, a battery of behavioral tests and in vivo magnetic resonance imaging (MRI) was used to investigate the postnatal consequences of prenatal exposure to lower doses of VPA in mice in early and late gestation. The effects of VPA were examined in female and male mice at juvenile and adult ages. The main findings were, that low doses of VPA in early or late gestation cause no physical malformation and no gross neurological functional impairments, but induce behavioral abnormalities and neuroanatomical differences related to autism. Generally, VPA-treated mice exhibited lower motor activities and higher anxiety levels in the open field test; dislike of novelty in the novel abject exploration test; higher startle response and sensorimotor gating differences; decreased responses to non-social and social odors in the olfactory test; and volumetric changes in brain structures similar to those found in autism. However, the timepoint of exposure, dose of VPA, sex and age of testing influenced the phenotypic outcome. Although largely neglected in previous studies, late gestation exposure to VPA elicited an autistic phenotype. Surprisingly, given the male bias in autism, female mice were often more ‘sensitive’ to VPA. Although the present studies had some limitations, these experiments confirmed that low dose VPA in pregnancy could trigger behavioral abnormalities and brain anatomical differences in mice that resembled a range of features of autism. Importantly, these behaviors were unconfounded by ‘gross’ neurological or physical abnormalities. Further studies to investigate the cellular mechanisms underlying the low dose VPA phenotype will therefore be helpful to shed light on possible causal pathways with specific relevance to autism. / published_or_final_version / Psychiatry / Doctoral / Doctor of Philosophy

Objective: To present a systematic review of existing literature that investigates biological plausibility of prenatal hazardous air pollutants’ (HAPs) exposure, in the etiology of autism spectrum disorder (ASD) and related outcomes. Method: Electronic databases Pubmed, Biomed Central and National Database for Autism Research, and grey literature pertaining to air pollution association with ASD and related outcomes were searched using specific keywords. The search included 190 HAPs as defined by The Clean Air Act Amendments of 1990 [U.S.Environmental Protection Agency (EPA) 1994] including air pollutants CO, SO2, NOx, O3 and Particulate Matter (PM). Studies selected for systematic review were assessed on quality and causality. Result: Total of 628 articles from electronic search and 16 articles from grey literature were retrieved. 12 studies that cleared the inclusion and exclusion criteria were systematically reviewed using the PRISMA checklist. Outcomes considered included ASD, Attention Deficit Hyperactivity Disorder, social behavior, social interaction, child behavior, communication, cognitive development, attention problems, mental and psychomotor development, and social competence. Studies were from two countries, United States of America and Spain. Study design was case control and cohort study. Follow up duration for cases ranged from in-utero to less than 9 years. Exposure was measured in ambient air using predictive models and cord blood. Although there were discrepancies in the studies, related to strength of association, analysis and covariates adjusted, the association between air pollution and ASD related outcomes could not be dismissed. Most studies lacked information on blinding when quality was assessed and lacked consistency when assessed on causality, while scored well on temporality and biological plausibility. Discussion: Evidence suggests HAPs are capable of transplacentally affecting cognitive function, especially traffic related pollutants. Study design, sample size, response rate, exposure misclassification, failing to adjusting covariates related to lifestyle, nutrition and other chemical exposures have influenced the estimates and the strength of association. Shortcomings of this review are the English language restriction and single reviewer on study selection process and assessments. Immuno-toxic, neuro-toxic and endocrine disrupting properties of these HAPs necessitates comprehensive prospective studies especially in Hong Kong with the rising prevalence of ASD and ever high reported air pollution indexes. Conclusion: Repeated studies were carried out on the same cohorts and studies were concentrated in U.S.A. On account of a lack of consistency, it is difficult to confirm whether air pollution is a plausible candidate for prenatal exposure in ASD. (Abstract of 391 words) / published_or_final_version / Public Health / Master / Master of Public Health

Schizophrenia and autism are psychiatric disorders with a presumed neurodevelopmental origin, characterised by clinical features and aetiologies that overlap at multiple levels. In addition to genetic susceptibility, epidemiological studies revealed an association between environmental factors and these disorders. Immune activation in response to infection at early gestation has been identified as one of the key risk factors. Little is known about the underlying mechanism during maternal immune activation (MIA), but extrinsic apoptotic dysregulation has been postulated to play a role in MIA infection. In particular, emerging studies suggest apoptosis without triggering whole cell demise, namely synaptic apoptosis, is a potential event that leads to the abnormal behaviours in the affected offspring. In this study, C57BL/6N mice model was employed to investigate the impacts of viral mimetic polyriboinosinic-polyribocytidylic acid (Poly I:C) exposure at gestation day 9 in the resultant male offspring in adulthood in vivo by different parameters, including magnetic resonance imaging (MRI), behavioural tasks that assess sensorimotor gating, exploratory and anxiety behaviours, and protein quantification in the apoptotic pathway. In parallel, the direct effect of Poly (I:C) treatment for 24 hours on extrinsic apoptotic proteins were determined in primary cortical neurons in vitro. It was hypothesised that MIA would result in brain volumetric changes subsequent to behavioural anomalies in the adult offspring with maternal exposure to Poly (I:C), for which abnormalities are normally pronounced by that time. In addition, the hypothesis that foetuses exposed to Poly (I:C) in early gestation stage would have increased expression level of apoptotic proteins of extrinsic types, namely Fas receptor, caspase-8 and the death effector caspase-3. This study found that, although male adult offspring with early maternal exposure to Poly (I:C) had an increase in raw whole brain volume, this was not significant when body weight was included as a covariable. However, prenatal exposure caused behavioural features similar to those reported in schizophrenia and autism such as prepulse inhibition deficits, increased anxiety-level and higher locomotor activity in response to amphetamine challenge. On the other hand, a marked augmentation in caspase-8 level without any significant changes in Fas or caspase-3 was observed in the adult hippocampus. No alterations in the expression of selected apoptotic proteins were found in the embryonic cortical cells. Overall the present studies suggested that acute exposure to infection during early fetal development causes a range of aberrations in brain anatomy, behaviour and biochemistry that are of relevance to the pathophysiology of schizophrenia and autism. The results suggest a potential involvement of synaptic apoptosis in cellular events underlying neurodevelopmental disorders. / published_or_final_version / Psychiatry / Master / Master of Philosophy