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Candidate micro- and macro- structural biomarkers of autism spectrum disorders
AuthorManierka, Marena Sylvia
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Autism spectrum disorders (ASD) continue to grow in prevalence, constituting a global health care issue. Neuroinflammation is now believed to play a critical role in ASD pathology and has yielded several potential biomarkers that could improve understanding of ASD mechanisms and enhance diagnostic specificity. Two of these markers show particular potential; microscopic cortical changes to microglial populations and macroscopic changes to diffusion within the brain’s white matter tracts. Greater understanding of exactly where within the ASD cortex microglial populations are disrupted may improve understanding of how glial inflammation contributes to the underlying pathological mechanisms of this disorder. However, observing glial inflammation in living populations is often impractical or impossible. Changes to white matter diffusion can be easily observed using non-invasive magnetic resonance imaging techniques. Establishing an ASD-specific profile of white matter diffusion abnormalities could allow traditional behavioral diagnostic criteria to be supplemented with diffusion imaging, improving overall diagnostic specificity. This project contains three aims examining microglial and white matter tract disruptions as specific biomarkers of ASD. Aim 1 assessed microglial changes in ASD in the superficial grey matter (layers II/III) of the temporal and parietal cortex; these cortical layers are critical to integration of sensory information and have theoretical relevance to ASD characteristics. Aim 2 examined glial disruptions in ASD in the grey-white matter boundary within the temporal cortex; this boundary region shows disorganization in ASD and is critically involved in early development of cortical connections. Aim 3 examined macroscopic disruptions in white matter diffusion to identify tract-specific changes that differentiate ASD adults from both schizophrenia and neurotypical controls. Results of Aims 1 and 2 suggest individuals with ASD show increased density and size of microglia in the superficial cortical layers, but no changes to glial populations in the grey-white matter boundary. Microglial changes in the superficial cortical grey matter may have special relevance to the pathological mechanisms underlying ASD. Results of Aim 3 indicate that white matter diffusion changes in ASD are relatively subtle, however, changes in several tracts may provide a useful marker to distinguish adults with ASD from those with schizophrenia. These diffusion-based markers may be a useful method of differentiating between alternative diagnoses in adults, especially where overlapping behavioral symptoms make it difficult to distinguish between schizophrenia and ASD. Observed on both a micro- and macro-scopic level, the markers examined in this dissertation suggest neuroinflammatory changes to the brain may be a core feature of ASD. Although additional work is required to establish these as general markers of mechanism and diagnostic status within the broader ASD population, the results of this study are a promising step in establishing biological markers to improve both understanding and identification of ASD.