Physiological Correlates of Social Avoidance Behavior in Children and Adolescents With Fragile X Syndrome

Objective: To investigate whether eye-gaze avoidance, a striking phenotypic feature in fragile X syndrome (FXS), is associated with high levels of hyperarousal during social interactions with others. To date, almost all studies in this area have been confounded by inclusion of task demands in addition to social demands. Method: We monitored the cardiovascular activity and eye-gaze avoidance of 50 boys and girls with FXS aged 5 to 20 years during a 25-minute intensive social interaction session with an unfamiliar experimenter. To control for possible family and genetic factors in cardiovascular activity, we compared each child with FXS with their same-sex typically developing biological sibling. Results: Participants with FXS obtained significantly higher heart rates, lower vagal tone, and lower heart rate variability estimates both at baseline and during the social interaction session compared with their typically developing siblings. Although eye-gaze avoidance occurred at significantly higher levels in the children with FXS, this behavior decreased slightly over the course of the session (a warm-up effect) and did not seem to be associated with cardiovascular activity. In the girls with FXS, higher levels of the fragile X mental retardation protein were associated with higher (and more typical) heart rate variability. Conclusions: These data suggest that both sympathetic and parasympathetic nervous systems are dysregulated in FXS. However, given that prolonged exposure to social demands does not inevitably lead to increased anxiety or hyperarousal, professionals should not be deterred from providing much needed social skills interventions for individuals with FXS. J. Am. Acad. Child. Adolsc. Psychiatry, 2009;48(3):320-329.