Pupil size and pupillary light reflex in early infancy: heritability and link to genetic liability to schizophrenia

Measures based on pupillometry, such as the pupillary light reflex (PLR) and baseline pupil size, reflect physiological responses linked to specific neural circuits that have been implicated as atypical in some psychiatric and neurodevelopmental conditions.

We investigated the contribution of genetic and environmental factors to the baseline pupil size and the PLR in 510 infant twins assessed at 5 months of age (281 monozygotic and 229 dizygotic pairs), and its associations with common genetic variants associated with neurodevelopmental (autism spectrum disorder and attention deficit hyperactivity disorder) and mental health (bipolar disorder, major depressive disorder and schizophrenia) conditions using genome-wide polygenic scores (GPSs).

Univariate twin modelling showed high heritability at 5 months for both pupil size (h²  = .64) and constriction in response to light (h²  = .62), and bivariate twin modeling indicated substantial independence between the genetic factors influencing each (r_G  = .38). A statistically significant positive association between infant tonic pupil size and the GPS for schizophrenia was found (β = .15, p = .024), while there was no significant association with the GPS for autism or any other GPSs.

This study shows that some pupil measures are highly heritable in early infancy, although substantially independent in their genetic etiologies, and associated with common genetic variants linked to schizophrenia. It illustrates how genetically informed studies of infants may help us understand early physiological responses associated with psychiatric disorders which emerge much later in life.