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

Abstract

Background: 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. Methods: 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). Results: Univariate twin modelling showed high heritability at 5 months for both pupil size (h 2 = .64) and constriction in response to light (h 2 = .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 (b = .15, p = .024), while there was no significant association with the GPS for autism or any other GPSs. Conclusions: 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.

Genetic and environmental contributions to individual differences in visual attention and oculomotor control in early infancy

“…While some twin studies on psychometric traits (i.e. IQ) suggest significant contributions from shared environment in early life 39,40 our results are in line with those from previous twin studies of eye movements and of early cognitive ability in infants 60 reporting none or marginal influence of shared environment 11,23,24,58,59 .…”

“…While unique environment effects may include different stable and temporary factors common to infant research that are not shared in a family (i.e. mood and/or measurement error linked to the eye tracker) 58,59 , the relatively high heritability speaks to the reliability of the measures studied here. In turn, contrary to our hypothesis, we found no evidence of shared environment influences in any of the measures.…”

Blink-induced changes in pupil dynamics are consistent and heritable

“…In a previously study conducted in a large cohort of young Chinese twins (Guangzhou Twin Project; 309 monozygotic (MZ) and 165 dizygotic (DZ) pairs [21]) heritability was found to be approximately 60% for iris thickness and pupil diameter [22]. A study using a large cohort of twin infants (BabyTwins Study Sweden (BATSS), [23]; 510 infant twins assessed at 5 months of age; 281 monozygotic and 229 dizygotic pairs) found that baseline tonic pupil size and pupillary light re ex (PLR) were highly heritable (pupil size, 64% and constriction in response to light, 62%) and linked to genome-wide polygenic risk (PLR) scores for schizophrenia [24]. Another study on 326 female twins (mean age 64 years) from the TwinsUK Adult Twin Registry [25], reported that resting pupil size in complete darkness was strongly heritable with additive genetic effects explaining up to 86% of the variance and environmental factors explaining only 14% of the variability, and for between 31 and 60% of the variability in the PLR [26].…”