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Description
With a growing number of adults with autism spectrum disorder (ASD), more and more research has been conducted on majority male cohorts with ASD from young, adolescence, and some older age. Currently, males make up the majority of individuals diagnosed with ASD, however, recent research states that the gender ga

With a growing number of adults with autism spectrum disorder (ASD), more and more research has been conducted on majority male cohorts with ASD from young, adolescence, and some older age. Currently, males make up the majority of individuals diagnosed with ASD, however, recent research states that the gender gap is closing due to more advanced screening and a better understanding of how females with ASD present their symptoms. Little research has been published on the neurocognitive differences that exist between older adults with ASD compared to neurotypical (NT) counterparts, and nothing has specifically addressed older women with ASD. This study utilized neuroimaging and neuropsychological tests to examine differences between diagnosis and sex of four distinct groups: older men with ASD, older women with ASD, older NT men, and older NT women. In each group, hippocampal size (via FreeSurfer) was analyzed for differences as well as correlations with neuropsychological tests. Participants (ASD Female, n = 12; NT Female, n = 14; ASD Male, n = 30; NT Male = 22), were similar according to age, IQ, and education. The results of the study indicated that the ASD Group as a whole performed worse on executive functioning tasks (Wisconsin Card Sorting Test, Trails Making Test) and memory-related tasks (Rey Auditory Verbal Learning Test, Weschler Memory Scale: Visual Reproduction) compared to the NT Group. Interactions of sex by diagnosis approached significance only within the WCST non-perseverative errors, with the women with ASD performing worse than NT women, but no group differences between men. Effect sizes between the female groups (ASD female vs. NT female) showed more than double that of the male groups (ASD male vs. NT male) for all WCST and AVLT measures. Participants with ASD had significantly smaller right hippocampal volumes than NT participants. In addition, all older women showed larger hippocampal volumes when corrected for total intracranial volume (TIV) compared to all older men. Overall, NT Females had significant correlations across all neuropsychological tests and their hippocampal volumes whereas no other group had significant correlations. These results suggest a tighter coupling between hippocampal size and cognition in NT Females than NT Males and both sexes with ASD. This study promotes further understanding of the neuropsychological differences between older men and women, both with and without ASD. Further research is needed on a larger sample of older women with and without ASD.
ContributorsWebb, Christen Len (Author) / Braden, B. Blair (Thesis advisor) / Azuma, Tamiko (Committee member) / Dixon, Maria (Committee member) / Arizona State University (Publisher)
Created2019
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Description
Autism shows a pronounced and replicable sex bias with approximately three-to-four males diagnosed for every one female. Sex-related biology is thought to play a role in the sex bias, such that female biology may be protective and/or male biology may increase vulnerability to autism in the context of similar genetic

Autism shows a pronounced and replicable sex bias with approximately three-to-four males diagnosed for every one female. Sex-related biology is thought to play a role in the sex bias, such that female biology may be protective and/or male biology may increase vulnerability to autism in the context of similar genetic risk. Beyond etiology, sex-related biology has also been implicated in lifespan risk for health and psychiatric conditions that show common co-morbidity in autism. Thus, understanding how sex-related biology impacts autism etiology and progression has important implications for prognosis and treatment. Neuroimaging offers a powerful tool for in-vivo characterization of brain-based sex differences in autism, especially given emerging efforts to develop large, well-characterized longitudinal samples. To date, however, neuroimaging studies have shown mixed and inconsistent findings, which remain challenging to integrate in the broader literature context. In a recent systematic review of neuroimaging studies of typical sex differences, few to no replicable effects were found beyond brain size, suggesting the brain is not “sexually dimorphic.” Instead, it is argued that the brain is a “mosaic” of features from various sources, including masculine and feminine biological processes as well as individual genetics and environment. Thus, designing neuroimaging studies that are sensitive to brain-based sex differences in autism likely requires careful study design and analytical method selection. Through a series of studies, the overarching dissertation aim was to identify optimal methods for characterizing neuroimaging-based sex differences in autism and to test these methods in preliminary samples. Study 1 comprised a systematic review of studies examining neuroimaging-based sex differences in autism with the aim of identifying optimal study designs, neuroimaging modalities, and analytical methods. Study 2 focused on examining the sensitivity of a connectome-wide approach to identify functional connectivity hubs underlying sex-biased behavior associated with autism (e.g., camouflaging). Study 3 used a connectome-wide functional connectivity approach to characterize sex differences in longitudinal changes associated with autistic traits vs. categorical diagnosis. These studies suggest that optimizing study design and methods improves identification of biologically plausible and clinically meaningful brain sex differences in autism. The relevance of findings to etiology and prognosis are discussed.
ContributorsWalsh, Melissa (Author) / Braden, B. Blair (Thesis advisor) / Azuma, Tamiko (Committee member) / Rogalsky, Corianne (Committee member) / Arizona State University (Publisher)
Created2022