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

BackgroundEye movement tracking non-invasively captures subtle cognitive and neural differences. Fixation stability, the ability to maintain steady visual fixation, may serve as a transdiagnostic marker in major psychiatric disorders. This study evaluates fixation stability as a potential transdiagnostic endophenotype in families with multiple affected individuals. MethodsMonocular eye tracking data was recorded using infrared cameras while participants fixed their gaze on a stimulus in trials with and without distractors. The fixation stability (FS) performance was compared across 449 individuals affected with major psychiatric disorders (26 Alzheimers 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) along with 145 healthy controls (HC). FS performance was compared across groups using a linear mixed effects model controlling for familiality, age and sex. ResultAffected 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. ConclusionsFS performance was impaired in major psychiatric disorders compared to FDRs and HC. Instead of an endophenotype, FS measures serve as illness markers. SCZ and BD showed the greatest deficits, highlighting the strong impact of psychotic conditions on visuoperceptual processing.