Abstract
Historically, the diagnosis of ASC has been strongly biased towards males. ASCs are highly heterogeneous regarding clinical presentation, and sex is one of the factors contributing to phenotypic heterogeneity. The primary topic of this PhD thesis is to investigate how ASC and the diagnostic presentation of its core and associated traits differ between sexes across development. We examined sex differences in the clinical presentation and the social cognitive profile to explore the underlying mechanisms of social and communication difficulties of ASCs across three developmental stages: childhood, adolescence, and adulthood. We used a large cohort of individuals from a single time point in the Longitudinal European Autism Cohort Project as part of the larger EU-AIMS autism consortium.I focused on two main objectives: a) To establish similarities and differences in the clinical profile between autistic males and females at different stages of development. We focused on key theories of sex differences (Extreme Male Brain (EMB) and Female Autism Phenotype (FAP)) and tested both core and associated symptoms. To establish the presence and origin of potential sex differences, we utilised a mix of analytical approaches, including item-level analyses, to investigate more nuanced differences/similarities in males and females across all age groups. b) Then, we examined sex differences in one social cognition (behavioural responses on standardised Theory of Mind tasks) across ASC/non-ASC to subsequently establish whether there are sex differences in ASC in ToM.
I first tested the key predictions of the EMB theory, finding a variation in sex differences, but when taking a more nuanced item-level approach, we found some key similarities/differences between males and females in all age groups, giving rise to the concept of subtle differences across clinical profiles in males and females. Next, I examined sex differences on the Camouflage Index (CF) (as per Lai, 2017) and age of diagnosis across autistic males and females. Despite finding females scoring higher on the CF, these differences were not significant. This was discussed in the context of potential ascertainment bias. Then, I systematically investigated the predictions that the EMB and FAB approaches to sex differences make about the core features of ASCs. I found mixed results across all age groups, though some overall evidence for relationships between systemising and repetitive behaviour in males in all age groups, but not females. I then examined sex differences in associated features relevant to ASC, focusing on ADHD and sensory processing. We found mixed results but an interesting association between sensory symptomatology and empathising and systemising. Finally, I explored the impact of sex and IQ on Theory of Mind (ToM) performance across ASC/non-ASC groups and the impact of sex and IQ. Our findings revealed considerable individual variability in ToM among autistic individuals.
This thesis concludes with a considered and critical general discussion of all findings and their relevance for clinical practice and future research. I consider the potential bias in sampling in current scientific studies and how this may affect finding systematic sex differences in large cohorts of this kind. I discuss the concept of a ‘female autism phenotype’ and the more nuanced and subtle approaches potentially needed for clinical assessment tools and individualised support.
| Date of Award | 1 Jul 2024 |
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| Original language | English |
| Awarding Institution |
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| Supervisor | Eva Loth (Supervisor) & Nick Puts (Supervisor) |