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

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.

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.

Affected individuals performed significantly poorly (fixation frequency(F=6.37, p_cor=0.003), median fixation duration(F=4.79, p_cor=0.009), saccade frequency(F=7.74, p_cor<0.001), mean saccade amplitude(F=4.92, p_cor=0.009), mean scanpath length(F=6.83, p_cor=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.

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.