The influence of environmental and genetic factors on behavior problems and autistic symptoms in boys and girls with fragile X syndrome.

OBJECTIVE: Fragile X syndrome, caused by mutations in a single gene of the X chromosome (FMR1), is associated with neurobehavioral characteristics including social deficits with peers, social withdrawal, gaze aversion, inattention, hyperactivity, anxiety, depression, and autistic behavior. However, there is considerable variability in the behavioral and psychiatric problems among children with this condition. The purpose of this study was to measure genetic and environmental factors influencing behavior problems and autistic symptoms in children with fragile X syndrome. DESIGN: We conducted an in-home evaluation of 120 children (80 boys and 40 girls) with the fragile X full mutation and their unaffected siblings, including measurements of the FMR1 protein (FMRP), quality of the home environment, maternal and paternal psychopathology, effectiveness of educational and therapeutic services, and child behavior problems. RESULTS: Results of multiple regression analyses showed that for boys with fragile X, effectiveness of educational and therapeutic services and parental psychological problems predicted internalizing and externalizing types of problems, while the quality of the home environment predicted autistic behavior. For girls with fragile X, the results emphasized significant effects of FMRP on behavior, in particular social withdrawal and anxious/depressed behavior. CONCLUSIONS: These findings are among the first to link FMRP expression to behavior. They also emphasize the significance of home- and school-based environmental variables in the neurobehavioral phenotype and help to lay the foundation for studies designed to identify specific interventions for reducing problem behavior in children with fragile X syndrome.

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.