Impaired eye contact in the FMR1 premutation is not associated with social anxiety or the broad autism phenotype

Clin Neuropsychol. 2018 Aug-Oct;32(7):1337-1352. doi: 10.1080/13854046.2017.1384063. Epub 2017 Oct 3.


Objective: The Fragile X Mental Retardation-1 (FMR1) premutation is a common genetic abnormality, affecting ~1:150 women in the United States. Clinical neuropsychologists are becoming increasingly aware of their role in the clinical management of the FMR1 premutation, which is associated with risk for a range of cognitive, executive, neuromotor, and psychological impairments, including neurodegenerative disease. This study investigated atypical eye contact as a critical neuropsychological phenotype associated with the FMR1 premutation.

Methods: Thirty-eight women with the FMR1 premutation and 27 control women engaged in a 20-min conversational sample with an examiner. Eye contact quality was coded from the videotaped samples by blinded coders. Mixed models tested group differences in eye contact during the beginning and the end of the conversation. Social anxiety and broad autism phenotype (BAP) traits were tested as predictors of eye contact quality across the groups.

Results: Women with the FMR1 premutation exhibited significantly reduced eye contact during both the beginning and the end of the social interaction, despite a 'warm-up' effect where eye contact improved by the end of the interaction. Eye contact quality was not associated with social anxiety or BAP traits.

Conclusions: This study supports reduced eye contact as a phenotypic feature of the FMR1 premutation, which presents independent of social anxiety and the BAP. These findings contribute to a growing understanding of the neuropsychological phenotype of the FMR1 premutation, which has public health implications given that >1 million individuals in the United States carry this genetic abnormality.

Keywords: Fragile X premutation; eye gaze; fragile X carriers; social gaze; social phobia.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anxiety / epidemiology
  • Anxiety / genetics*
  • Anxiety / psychology
  • Autistic Disorder / epidemiology
  • Autistic Disorder / genetics*
  • Autistic Disorder / psychology
  • Eye Movements / physiology*
  • Female
  • Fragile X Mental Retardation Protein / genetics*
  • Fragile X Syndrome / epidemiology
  • Fragile X Syndrome / genetics*
  • Fragile X Syndrome / psychology
  • Humans
  • Middle Aged
  • Neuropsychological Tests
  • Phenotype*


  • FMR1 protein, human
  • Fragile X Mental Retardation Protein