Associations Between Blunted Pupillary Constriction and Dilation in Individuals with Schizophrenia: Evidence of a Common Mechanism?

Background and hypothesis: Unpacking the pathophysiological mechanisms of schizophrenia is necessary for advancing prediction, prevention, and treatment efforts. Mechanisms can be identified using easy-to-use and scalable clinical biomarkers, which reflect illness processes. Pupillometry is one such biomarker. Blunted dilation related to cognitive demand has been interpreted as a metric of diminished effort in schizophrenia, while blunted constriction to light has been interpreted as a metric of altered autonomic balance in schizophrenia. However, these 2 sets of findings may also reflect a common mechanism of schizophrenia. Therefore, this study aimed to explore the association between blunted cognitive dilation and blunted constriction to light to provide a parsimonious mechanism of autonomic and effort disturbances experienced by individuals with schizophrenia.

Study design: We assessed light-induced constriction and cognitive dilation during a double-step task in individuals with schizophrenia (n = 84) and demographically matched healthy controls (HC, n = 69), compared these metrics between groups, and computed their correlation within each group.

Study results: Replicating prior findings, dilation and constriction were blunted in schizophrenia relative to HC. Blunted constriction and dilation were positively correlated in schizophrenia but not HC (although the 2 correlations did not differ significantly).

Conclusions: Findings provide, for the first time, preliminary support of a common mechanism linking blunted pupil constriction to light and dilation to cognitive demands in schizophrenia. We propose that individuals with schizophrenia may exhibit impaired top-down modulation of autonomic control. Future studies are needed to validate this proposed mechanism.