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Mapping neurodevelopmental trajectories: A focus on autism with comparisons to psychosis

Ashley, Sarah Ann; (2024) Mapping neurodevelopmental trajectories: A focus on autism with comparisons to psychosis. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

Both autism and schizophrenia are neurodevelopmental disorders. Autism is diagnosed early in childhood, whereas schizophrenia and psychotic disorders have a later onset in adolescence and early adulthood. A better understanding of the neurodevelopmental trajectories that underlie these disorders would provide insights into their underpinning biological mechanisms. Research indicates the neurodevelopmental abnormalities may also be present in participants with specific traits of autism or in participants with attenuated symptoms of schizophrenia. Autistic traits (e.g. social communication difficulties) can be measured psychometrically and are thought to lie on a continuum with normality. Psychotic experiences occur in 5-10% of the general population and are associated with an increased risk for developing schizophrenia. The thesis comprises of 4 studies: (1) A meta-analysis of total brain volume trajectories in autism spectrum disorder (ASD); (2) An investigational study charting head circumference trajectories from birth to age 15 years in individuals with autism and elevated autistic traits relative to controls; (3) An investigational study charting head circumference trajectories in participants with psychotic disorder and psychotic experiences relative to controls; (4) An investigational study using magnetic resonance imaging (MRI) to explore grey matter brain alterations associated with autistic traits. In chapter 2, I present a meta-analysis of longitudinal studies measuring total brain volume in ASD. I explore differences with controls at individual study timepoints as well as longitudinal changes over time. We find evidence of early brain overgrowth in ASD before the age of 5, but that changes in total brain volume over time were reduced, which is indicative of slowing or arrest of growth in ASD. Chapter 3 presents original research using data from the Avon Longitudinal Study of Parents and Children (ALSPAC). Using linear mixed effects models, we charted head circumference trajectories from birth to 15 years in individuals (a) with and without ASD, (b) and elevated autistic traits. ASD was linked to larger head circumference from birth to adolescence compared to controls, with a clear difference emerging at 2 months of age. Enlarged head circumference was more pronounced in those with ASD and comorbid cognitive learning needs. Children with autistic traits only, measured using the Social Communication Disorder Checklist (SCDC), had smaller head circumference compared to controls. Chapter 4 presents novel findings of head circumference trajectories associated with psychotic experiences. Psychotic experiences measured using the semi structured PLIKS interview in ALSPAC at age 18 were associated with reduced head circumference trajectories in females but increased trajectories in males compared to controls. However, operationally defined ‘psychotic disorder’ was associated with reduced head circumference in both sexes. A subset of this sample also had neuroimaging at age 21 years, showing psychotic disorder to be associated with reduced total intracranial volume and total grey matter volume. Finally, in chapter 5, we explore alterations in grey matter volume associated with autistic traits measured using the SCDC. We find that autistic traits are associated with grey matter volume alterations in frontal and parietal brain regions. These cortical regions are thought to contribute to deficits in higher-order cognitive functioning and atypical sensory processing. We did not find an association with total intracranial volume and total grey matter volume. These findings provide important insights into the neurodevelopmental trajectories underlying ASD and psychotic disorder. Both conditions are associated with atypical growth, with increased total brain volume and head circumference in ASD, whereas head circumference and total brain volume was reduced in psychotic disorder. Neurodevelopmental trajectories differ between ASD and those with autistic traits, as autistic traits were associated with reduced head circumference, and no difference in total brain volume, although alterations in brain regional volumes were found. When comparing psychotic disorder patients to participants with subthreshold psychotic experiences, females with psychotic experiences showed similar head circumference trajectories to those with psychotic disorder, whereas males with psychotic experiences showed larger head circumferences. Although reduced TIV and total grey matter volume was seen in psychotic disorder, no differences were found in participants with psychotic experiences compared to controls. In summary, more severe neurodevelopmental changes are present in ASD and psychotic disorder compared to those with sub-threshold traits.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Mapping neurodevelopmental trajectories: A focus on autism with comparisons to psychosis
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Copyright © The Author 2024. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Division of Psychiatry
URI: https://discovery.ucl.ac.uk/id/eprint/10200067
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