Towards understanding sex differences in autism spectrum disorders.

Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by social deficits, repetitive behaviours and lack of empathy. Its significant genetic heritability and potential comorbidities often lead to diagnostic and therapeutic challenges. This review addresses the biological basis of ASD, focusing on the sex differences in gene expression and hormonal influences. ASD is more commonly diagnosed in males at a ratio of 4:1, indicating a potential oversight in female-specific ASD research and a risk of underdiagnosis in females. We consider how ASD manifests differently across sexes by exploring differential gene expression in female and male brains and consider how variations in steroid hormones influence ASD characteristics. Synaptic function, including excitation/inhibition ratio imbalance, is influenced by gene mutations and this is explored as a key factor in the cognitive and behavioural manifestations of ASD. We also discuss the role of micro RNAs (miRNAs) and highlight a novel mutation in miRNA-873, which affects a suite of key synaptic genes, neurexin, neuroligin, SHANK and post-synaptic density proteins, implicated in the pathology of ASD. Our review suggests that genetic predisposition, sex differences in brain gene expression, and hormonal factors significantly contribute to the presentation, identification and severity of ASD, necessitating sex-specific considerations in diagnosis and treatments. These findings advocate for personalized interventions to improve the outcomes for individuals with ASD.

Evaluative contexts facilitate implicit mentalizing: relation to the broader autism phenotype and mental health.

One promising account for autism is implicit mentalizing difficulties. However, this account and even the existence of implicit mentalizing have been challenged because the replication results are mixed. Those unsuccessful replications may be due to the task contexts not being sufficiently evaluative. Therefore, the current study developed a more evaluative paradigm by implementing a prompt question. This was assessed in 60 non-autistic adults and compared with a non-prompt version. Additionally, parents of autistic children are thought to show a genetic liability to autistic traits and cognition and often report mental health problems, but the broader autism phenotype (BAP) is an under-researched area. Thus, we also aimed to compare 33 BAP and 26 non-BAP mothers on mentalizing abilities, autistic traits, compensation and mental health. Our results revealed that more evaluative contexts can facilitate implicit mentalizing in BAP and non-BAP populations, and thus improve task reliability and replicability. Surprisingly, BAP mothers showed better implicit mentalizing but worse mental health than non-BAP mothers, which indicates the heterogeneity in the broader autism phenotype and the need to promote BAP mothers' psychological resilience. The findings underscore the importance of contexts for implicit mentalizing and the need to profile mentalizing and mental health in BAP parents.