(Why) are there more men than women with autism? Sex differences in Autism: genes, brain and healthcare (SCANNER)

Autism Spectrum Disorder (ASD) is diagnosed far more often in males than in females. However, the mechanisms underlying this prevalence disparity remain elusive, significantly impeding development of targeted interventions and diagnostic tests for autism. We aim to understand how genetic, neurophysiological and behavioural sex differences contribute to the presence and severity of autism symptoms, and to distinguish these biological factors from potential diagnostic bias. Our long-term goal is to improve the ASD diagnostic process, taking sex differences into account. Therefore, this project directly addresses two NWA questions: ‘How do neurological, psychiatric, and mental disorders arise, and how can we prevent, mitigate, or cure them?’, and ‘How will our knowledge of genetics play a role in analysing, screening for and treating disease?’. Both questions fall under our primary route: ‘NeurolabNL’, and the secondary route: ‘Healthcare research, sickness prevention and treatment’.
Specifically, we will: (1) Identify genetic factors that influence autism symptom severity in males and females. (2) Investigate the causal role of early-life factors in autism sex differences. (3) Define sex-dependent differences in brain structure, connectivity and function in autism. (4) Determine sex-dependent behavioural manifestations of autism, employing data from large population cohorts: Netherlands Autism and Twin Registers, and Generation R, and develop sex-sensitive eHealth tools. We will focus on sensorimotor function, as deficits in this area are common but rarely quantified and suitable for the development of novel diagnostic tools. (5) Investigate the potential diagnostic bias that leads to underdiagnosis of females, and evaluate sex-sensitive eHealth tools for Dutch general practitioners, psychologists and psychiatrists.
This project combines the societal need for improved diagnosis of autism with the advancement of scientific understanding of the biological mechanisms underlying sex differences in this disorder. We will collaborate with autistic individuals, psychiatrists and general practitioners to design our studies and implement the findings.