A novel eye-tracking paradigm for indexing social avoidance-related behavior in fragile X syndrome

Fragile X syndrome (FXS) is characterized by hallmark features of gaze avoidance, reduced social approach, and social anxiety. The development of therapeutics to manage these symptoms has been hindered, in part, by the lack of sensitive outcome measures. This study investigated the utility of a novel eye-tracking paradigm for indexing social avoidance-related phenotypes. Adolescent/young adult-aged males with FXS (n = 24) and typical development (n = 23) participated in the study. Participants viewed faces displaying direct or averted gaze and the first fixation duration on the eyes was recorded as an index of initial stimulus registration. Fixation durations did not differ across the direction of gaze conditions in either group, although the control group showed longer initial fixations on the eyes relative to the FXS group. Shorter initial fixation on averted gaze in males with FXS was a robust predictor of the severity of their social avoidance behavior exhibited during a social greeting context, whereas parent-reported social avoidance symptoms were not related to performance in the semi-naturalistic context. This eye-tracking paradigm may represent a promising outcome measure for FXS clinical trials because it provides a quantitative index that closely maps onto core social avoidance phenotypes of FXS, can be completed in less than 20 min, and is suitable for use with individuals with low IQ.