Physiological regulation and social-emotional processing in female carriers of the FMR1 premutation

The FMR1 gene is associated with a wide range of clinical and cognitive phenotypes, ranging from intellectual disability and autism symptoms in fragile X syndrome (caused by the FMR1 full mutation), to a more varied, and still poorly understood range of clinical and cognitive phenotypes among carriers of the gene in its premutation state. Because the FMR1 premutation is relatively common among women (as high as 1 in 150), investigations of its phenotypic impact could have broad implications for understanding gene-behavior relationships underlying complex human traits, with potential clinical implications. This study investigated physiological regulation measured by pupillary responses, along with fixation patterns while viewing facial expressions among women who carry the FMR1 premutation (PM group; n = 47), to examine whether the FMR1 gene may relate to physiological regulation, social-emotional functioning, and social language skills (where subclinical differences have been previously reported among PM carriers that resemble those documented in autism-related conditions). Relative to controls (n = 25), the PM group demonstrated atypical pupillary responses and fixation patterns, controlling for IQ. In the PM group, pupillary response and fixation patterns were related to social cognition, social language abilities, and FMR1-related variation. Results indicate a pattern of atypical attention allocation among women who carry the FMR1 PM that could reflect different emotion-processing strategies mediated by autonomic dysregulation and the FMR1 gene. These findings lend insight into the FMR1 gene's potential contributions to complex human traits such as social emotional processing and social language.