Hypothalamic-pituitary-adrenal axis function in Fragile X Syndrome and its relationship to behaviour: A systematic review

Physiol Behav. 2016 Dec 1:167:341-353. doi: 10.1016/j.physbeh.2016.09.030. Epub 2016 Oct 5.

Abstract

Fragile X Syndrome (FXS) is characterised by features including anxiety and autistic-like behaviour, which led to early hypotheses that aberrant physiological arousal may underlie the behavioural phenotype. In line with this, several lines of evidence suggest that the hypothalamic-pituitary-adrenal (HPA) axis may be altered in the syndrome. This review collates evidence to determine the nature of HPA axis baseline activity and reactivity (as measured by glucocorticoid levels) differences in FXS, and its relationship to behaviour. Through a search of electronic databases, 15 papers were identified which provided data on humans with FXS or the FMR1 knockout mouse model. The findings across studies are mixed, though trends in the findings can be seen, including elevations in cortisol levels, particularly in males. Preliminary findings also highlight associations between cortisol levels and key behaviours associated with the syndrome, such as gaze avoidance. Areas for future research are discussed.

Keywords: Autism; Corticosterone; Cortisol; FMR1; FMRP; Fragile X Syndrome; Glucocorticoid; HPA; Hypothalamic-pituitary-adrenal axis; KO mouse; Systematic review.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Animals
  • Anxiety / etiology
  • Autistic Disorder / etiology
  • Behavior / physiology*
  • Databases, Bibliographic / statistics & numerical data
  • Disease Models, Animal
  • Fragile X Syndrome / complications
  • Fragile X Syndrome / genetics
  • Fragile X Syndrome / pathology*
  • Glucocorticoids / metabolism
  • Humans
  • Hypothalamo-Hypophyseal System / physiopathology*
  • Pituitary-Adrenal System / physiopathology*

Substances

  • Glucocorticoids