Two-month antipsychotic exposure induces domain-specific eye movement alterations in clinical high-risk individuals

While antipsychotic-induced eye movement alterations are well-documented in schizophrenia, their effects during the clinical high-risk (CHR) phase remain uncharacterized. This study examined the effects of two-month antipsychotic treatment on eye movement parameters in CHR individuals and their association with clinical outcome.

In this longitudinal cohort, 139 CHR individuals and 105 healthy controls completed baseline eye-tracking (fixation stability, free viewing, and smooth pursuit). CHR participants were reassessed at two months and followed for three years to track remission status. Linear mixed-effects models examined the effects of antipsychotic use, dose, and type on eye movement indicators, and a random forest model evaluated how changes in these indicators predicted clinical remission.

In the antipsychotic - treated subgroup, fixation stability featured more microsaccades, free viewing showed reduced saccade amplitude and velocity, and smooth pursuit showed increased velocity gain with reduced saccade amplitude, and these changes scaled with dose and varied by agent with the most pronounced effects for aripiprazole. A random forest classifier using two treatment-induced eye movement change values predicted 3-year clinical non-remission with an area under the receiver operating characteristic curve of 0.80.

Short-term antipsychotic exposure induced mixed eye movement alterations that were associated with non-remission at three-year follow-up. This finding provides a reference for the development of personalized risk stratification frameworks and targeted intervention strategies in CHR populations.