Hypersensitive pupillary light reflex in infants at risk for autism

Background: Post mortem brain tissue data and animal modeling work indicate cholinergic disruptions in autism. Moreover, the cholinergic system plays a key role in the early neurodevelopmental processes believed to be derailed early in life in individuals with the disorder. Yet, there is no data from human infants supporting a developmentally important role of this neurotransmitter system. Because the pupillary light reflex depends largely on cholinergic synaptic transmission, we assessed this reflex in a sample of infants at risk for autism as well as infants at low (average) risk. Methods: Ten-month-old infants with an older sibling with autism (n = 29, 16 females), and thus a genetic predisposition to developing the disorder themselves, were presented with white flashes on a computer monitor, and pupillary responses were captured using eye tracking. A control group matched on age and developmental level (n = 15, seven females) was also tested. Results: The siblings of children with autism had a faster and stronger pupillary light reflex compared to control infants. Baseline pupil diameter was equal in the two groups, ruling out tonic autonomic imbalance as an explanation for these differences. Conclusions: This study establishes that infant siblings of children with autism have hypersensitive pupillary light reflexes, a result which supports the view that altered sensory processing in infancy is associated with elevated autism risk. Moreover, the study indicates that individual differences in autism susceptibility are linked to differences in the cholinergic system during an early developmental period.