Delineating neurodevelopmental causal paths to autism symptoms in infancy

  • Awarded: 2017
  • Award Type: Pilot
  • Award #: 511504

Rapid progress in identifying penetrant and common genetic risk factors is yielding deep insights into putative molecular networks affected in autism spectrum disorder (ASD). However, despite the exquisite level of detail applied to the genetics of ASD, the phenotypes examined are almost universally based on behavioral symptoms manifested by children and adults. Given that peak expression of many ASD-related genes is prenatal, there is a hole in our ability to build mechanistic models of how genetic variation influences early brain development and results in ASD symptoms. Bridging this gap will allow us to develop new interventions targeted at the causal paths that lead to ASD symptoms in early development, in a window in which developmental plasticity is likely maximal.

Emma Meaburn and Emily Jones will test a specific causal path between genetic risk and behavioral symptoms: disruptions in the brain systems underpinning social attention. The researchers have chosen to focus on social attention because there is extensive evidence that infants and toddlers with ASD pay less attention to other people, and this could have cascading influences of later behavior by reducing opportunities for social learning1.

To achieve their aims, Meaburn and Jones will characterize common polygenic and rare penetrant ASD risk variants in a prospective cohort of infants at high and low risk of ASD, for whom extensive behavioral and neurocognitive measures of social attention are available throughout infancy and childhood2. Specifically, they will link common and rare genetic risk to variability in neurocognitive measures of infant social attention and later ASD symptoms, and identify protective factors that may boost social attention and support typical outcomes in infants at high genetic risk. Taken together, this represents a proof-of-principle study to determine the value of genetically informed prospective longitudinal designs for revealing causal paths to ASD.



1.Jones, E. J. H. et al. J. Child Psychol. Psychiatry 58, 270-281 (2017). PubMed
2.Elsabbagh, M. et al. Curr. Biol. 22, 338-342 (2012). 
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