Early Risk Markers of Social Anxiety in Infants with Fragile X Syndrome

Background: Fragile X syndrome (FXS) is a neurodevelopmental disorder that typically presents with intellectual disability and an increased prevalence of maladaptive behaviors (Cornish et al., 2013). FXS is the most common genetic cause of autism spectrum disorder (ASD) accounting for 2-6% of ASD cases (Cohen et al., 2005). Both FXS and ASD have high comorbidities with anxiety disorders which often are not diagnosed until later in development (Cordeiro et al., 2010; Kessler et al., 2005). Given that early features of social anxiety are present before formal diagnoses, prospective studies of infants with FXS provides a unique opportunity to study the earliest predictors of anxiety. In typically developing (TD) infants, elevated fear and atypical physiological regulation (e.g., respiratory sinus arrhythmia, RSA) have been identified as early markers of the later emergence of social anxiety. (Booker et al., 2013). No studies have examined behavioral fear or physiological regulation as risk markers of social anxiety in infants with FXS.

Objectives: The current study uses a bio-behavioral approach to investigate differences in social fear responses in 12-month-old infants. We hypothesized that physiological regulation during social interactions is disrupted in FXS, causing them to exhibit a dampened physiological response to a novel social situation. Additionally, we believed that FXS infants would have higher parent reported fear in comparison to TD.

Methods: Participants included 18 infants with FXS (Male: n =12, chronological age: M =13.01 months, SD=1.02) and 30 TD infants (Male: n = 23, chronological age M=12.41 months, SD=0.61). The fear subscale from the Infant Behavior Questionnaire-Revised (IBQ-R) reflects scores associated with both social and non-social fear. Physiological response to a novel social scenario was measured via heart activity monitor during a baseline period and during the Stranger Task of the LABTAB (Goldsmith & Rothbert, 1996). This task is designed to elicit a social fear response in young children. RSA reactivity was computed as the change in RSA from baseline to stranger task.

Results: The difference between groups on the IBQ-R was not significant, t(33) = 0.37, p > 0.05. Moreover, there was no difference between groups in RSA reactivity F(1,36) = .14, p > 0.05. Paired sample t-tests were conducted between baseline and stranger RSA for each group. The TD group showed a significant decrease from baseline (M = 4.61, SD = 1.03) to stranger task (M = 3.84, SD = .0.76), t(22) = -3.80, p < .001. The FXS group did not show a difference between baseline (M = 4.49, SD = 1.41) and stranger task (M = 3.79.50, SD = 1.43), t(15) = 2.08, p > .05.

Conclusions: These results provide intriguing insights into the early physiological risk markers of social fear. Despite the lack of elevated fear in the FXS group, the blunted RSA response to social fear shows a potential early biomarker of social anxiety. Having a physiological biomarker reflecting prodromal symptomology could be instrumental to early identification and treatment of social anxiety in FXS and other high risk populations like ASD. Future studies, should investigate infant’s behavioral responses in tandem with RSA regulation.