FXS Patients’ Social Deficits are Linked to Social Anxiety, Eye-tracking Study Says

Using eye-tracking technologies, researchers have shown that patients with fragile X syndrome avoid direct eye contact and show signs of social deficits linked to social anxiety. But they do so without the prominent reduction in social interest associated with autism spectrum disorder.

The study, “Differentiating social preference and social anxiety phenotypes in fragile X syndrome using an eye gaze analysis: a pilot study,” was published in the Journal of Neurodevelopmental Disorders.

Fragile X syndrome (FXS) is the most common single genetic cause of autism spectrum disorder (ASD). FXS patients often exhibit austism-like features, including impaired social skills, hyperactivity, and repetitive behaviors, together with intellectual and developmental disabilities, such as speech.

Anxiety is one of the hallmarks of FXS, with 70% of men and 56-77% of women reporting symptoms associated with social anxiety and specific phobias, such as avoiding direct eye contact, shyness, hand-flapping and hand biting.

In this study, a team of investigators from the University of Cincinnati set out to investigate social anxiety features among individuals with FXS and idiopathic (of unknown cause) ASD to typically developing controls (TDC) using custom-designed eye-tracking technologies.

The study enrolled 17 individuals with FXS, 17 with ASD, and 17 age- and sex-matched TDC who performed emotional face and social preference eye-tracking tasks to evaluate gaze aversion and social interest, respectively.

The emotional face task consisted of looking at 12 faces of men and women displaying different emotions, while the social preference task consisted of looking at images depicting social interactions or geometric patterns.

In addition, researchers analyzed patients’ intellectual capabilities and behavior based on cognitive tests and on feedback provided by their caregivers.

Results showed that patients with FXS avoided direct eye contact when looking at emotional face images, focusing on the subjects’ mouth instead, compared to TDCs. Eye-tracking results, specifically fewer fixations to the eyes, correlated with social anxiety, communication deficits and behavioral issues.

In the social preference task, ASD patients showed significantly less social interest compared to FXS patients and controls.

“The novel finding of this study was the observation of gaze aversion but without the reduced social interest (…) of ASD in the FXS patients,” researchers wrote.

“Social interest and gaze aversion eye tracking paradigms provide novel, valid strategies for [explaining] the mechanistic differences between FXS and idiopathic ASD with regard to causes for their social symptomology,” they added.