Gaze fixation stability is a transdiagnostic marker of major psychiatric disorders: A high-density family-based study.

BACKGROUND: Eye movement tracking non-invasively captures subtle cognitive and neural differences. Fixation stability (FS), the ability to maintain steady visual fixation, has been proposed as a transdiagnostic marker in major psychiatric disorders. This study evaluates fixation stability as a canidate transdiagnostic endophenotype in individuals from multiplex families with major psychiatric disorders. METHODS: Monocular eye tracking data were recorded using infrared cameras while participants fixed their gaze on a stimulus in trials with and without distractors. FS measures were compared across affected 449 individuals (26 Alzheimer's Dementia (AD), 89 schizophrenia (SCZ), 116 bipolar disorder (BD), 98 obsessive-compulsive disorder (OCD), and 120 substance-use disorder (SUD)), 442 unaffected first degree relatives (FDRs) and 145 healthy controls (HC). FS performance was compared across groups using a linear mixed effects model controlling for familiality, age and sex. RESULT: Affected individuals performed significantly poorly (fixation frequency(F=6.37, pcor=0.003), median fixation duration(F=4.79, pcor=0.009), saccade frequency(F=7.74, pcor<0.001), mean saccade amplitude(F=4.92, pcor=0.009), mean scanpath length(F=6.83, pcor=0.003)) in the trials with distractors when compared to FDRs and HC. The performance of FDRs and HC did not differ significantly from that of the other. Furthermore, in a cross-diagnostic comparison, impaired performance was observed only in SCZ and BD, with both performing significantly worse than SUD, OCD, and HC. CONCLUSIONS: FS was impaired in major psychiatric disorders, especially SCZ and BD. No difference noted between FDRs and HC suggesting it as an illness-related, but not a endophenotypic marker. Further studies accounting for disorder-specific familial risk are needed to clarify its endophenotypic potential.