NNL.20.011 – Why are there more men than women with autism? Searching the genes and the brain.

Route: NeuroLabNL: the ultimate living lab for brain, cognition and behavioural research

Cluster question: 083 How do neurological, psychiatric, and mental disorders arise, and how can we prevent, mitigate, or cure them?

Autism spectrum disorder (ASD) is diagnosed four times more often in men than in women. This ratio is consistently seen in different countries and populations. Yet, the mechanisms underlying this male bias remain elusive.
Researchers have shown that brain connectivity and function is altered in individuals with ASD, and identified over a hundred ASD risk genes but sex is rarely considered a variable in these studies.
The objective of this proposal is to understand how genetic and neurophysiological differences between men and women contribute to the presence and severity of ASD symptoms. We will focus on sensorimotor deficits that often accompany core ASD traits and can be measured more objectively than social behaviours. Our long-term goal is to improve the diagnosis of ASD and identify new possible treatment targets.
To study the behavioural manifestation of ASD, we will employ data from several large, Dutch cohorts: Netherlands Autism Register, Developmental Coordination Disorder study, and Netherlands Twin Register. We will explore how natural variation in developmental exposure to different sex hormones affects ASD symptom severity and sensorimotor function. We will also study the degree to which genomic and epigenomic insults predict ASD scores in both sexes. Next, we will use imaging to explore brain connectivity and function in males and females with ASD. In parallel, we will investigate the neural and genetic mechanisms at the causal level in ASD mouse models. Animal studies enable targeted brain circuit manipulations and open a possibility for rescue experiments. Linking to human imaging, we will functionally investigate the relevant circuits, now at the level of cells.
This project provides a unique opportunity to combine the societal need for improved diagnosis of a prevalent neurodevelopmental disorder with the advancement of scientific understanding of the fundamental mechanisms underlying sex differences in ASD.

Keywords

ASD, brain imaging, genetics, murine models, population cohorts, sex differences

Other organisations

Cognition and Behaviour;, Donders Institute for Brain, Radboud Medical Center (RUMC), Spinoza Centre for Neuroimaging, Vrije Universiteit Amsterdam (VU)

Submitter

Organisation Erasmus MC (EUR)
Name Dr. Aleksandra Badura
E-mail a.badura@erasmusmc.nl
Website https://neuro.nl/research/badura