Abstract

To examine the association between limbic-hypothalamic-pituitary-adrenal (L-HPA) axis reactivity and social behavior in children with fragile X syndrome (FXS). Salivary cortisol changes and concurrent anxiety-related behaviors consistent with the behavioral phenotype of FXS were measured in 90 children with the fragile X full mutation and their 90 unaffected siblings during a social challenge task in the home. Boys and girls with FXS demonstrated more gaze aversion, task avoidance, behavioral signs of distress, and poorer vocal quality than the unaffected siblings. Multiple regression analyses showed that after accounting for effects of IQ, gender, age, quality of the home environment, and basal cortisol level, cortisol reactivity to the task was significantly associated with social gaze in children with FXS. The most gaze-aversive children with FXS had cortisol reductions, whereas those with more eye contact demonstrated the most cortisol reactivity. Unaffected siblings demonstrated an opposite pattern in which less eye contact was associated with increased cortisol reactivity. Results of the study suggest a unique relation between abnormal gaze behavior and L-HPA mediated stress reactivity in FXS.

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