Cortisol and social stressors in children with fragile X: a pilot study.

Evidence of neuroendocrine dysfunction, behavioral features of social anxiety and avoidance, and neuroanatomical abnormalities suggest that abnormal hypothalamic-pituitary-adrenal (HPA) function may be a component of the fragile X (fra X) syndrome. In this preliminary study, salivary cortisol levels of males (n = 8, mean age = 13.5 yr) and females (n = 7, mean age = 13.9 yr) with the fra X full mutation were studied for 3 days. Day 1 was an experimental day, during which subjects experienced a Social Stressor task midmorning. Days 2 and 3 were routine days, during which the subjects were engaged in their typical activities. Saliva samples were collected before breakfast, lunch, dinner, and bedtime. On the experimental day, the prelunch sample collection occurred 30 and 90 minutes after the Social Stressor task. Compared with children's norms, the combined group of males and females with fra X had significantly higher cortisol levels in the prelunch and the prebedtime samples for the routine days. Comparisons between the two fra X groups for the experimental day revealed similar diurnal patterns for cortisol level. However, compared with females with fra X, males with fra X had significantly higher cortisol levels at two points during the day: 30 minutes after the social stressor and at bedtime. These preliminary data suggest that individuals with fra X have abnormal HPA function. Understanding the relations among HPA dysfunction, abnormalities in brain structure and/or function, and maladaptive behavior and cognition in fra X could inform the design of early interventions using pharmacological or environmental measures designed to normalize neuroendocrine function.