Cortisol and behavior in fragile X syndrome

David R Hessl, B. Glaser, J. Dyer-Friedman, C. Blasey, T. Hastie, M. Gunnar, A. L. Reiss

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Abstract

Objective: The purpose of this study was to determine if children with fragile X syndrome, who typically demonstrate a neurobehavioral phenotype that includes social anxiety, withdrawal, and hyper-arousal, have increased levels of cortisol, a hormone associated with stress. The relevance of adrenocortical activity to the fragile X phenotype also was examined. Method: One hundred and nine children with the fragile X full mutation (70 males and 39 females) and their unaffected siblings (51 males and 58 females) completed an in-home evaluation including a cognitive assessment and a structured social challenge task. Multiple samples of salivary cortisol were collected throughout the evaluation day and on two typical non-school days. Measures of the fragile X mental retardation (FMR1) gene, child intelligence, the quality of the home environment, parental psychopathology, and the effectiveness of educational and therapeutic services also were collected. Linear mixed-effects analyses were used to examine differences in cortisol associated with the fragile X diagnosis and gender (fixed effects) and to estimate individual subject and familial variation (random effects) in cortisol hormone levels. Hierarchical multiple regression analyses were conducted to determine whether adrenocortical activity is associated with behavior problems after controlling for significant genetic and environmental factors. Results: Results showed that children with fragile X, especially males, had higher levels of salivary cortisol on typical days and during the evaluation. Highly significant family effects on salivary cortisol were detected, consistent with previous work documenting genetic and environmental influences on adrenocortical activity. Increased cortisol was significantly associated with behavior problems in boys and girls with fragile X but not in their unaffected siblings. Conclusions: These results provide evidence that the function of the hypothalamic-pituitary-adrenal axis may have an independent association with behavioral problems in children with fragile X syndrome.

Original languageEnglish (US)
Pages (from-to)855-872
Number of pages18
JournalPsychoneuroendocrinology
Volume27
Issue number7
DOIs
StatePublished - Oct 2002
Externally publishedYes

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Keywords

  • Behavior
  • Cortisol
  • FMRP
  • Fragile X syndrome
  • Neuroendocrine
  • Stress

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Psychiatry and Mental health
  • Biological Psychiatry
  • Endocrine and Autonomic Systems
  • Psychology(all)

Cite this

Hessl, D. R., Glaser, B., Dyer-Friedman, J., Blasey, C., Hastie, T., Gunnar, M., & Reiss, A. L. (2002). Cortisol and behavior in fragile X syndrome. Psychoneuroendocrinology, 27(7), 855-872. https://doi.org/10.1016/S0306-4530(01)00087-7