Decreased functional brain response to emotional arousal and increased psychiatric symptomology in FMR1 premutation carriers

Psychiatry Res Neuroimaging. 2019 Mar 30:285:9-17. doi: 10.1016/j.pscychresns.2019.01.011. Epub 2019 Jan 29.


The FMR1 premutation is an expansion of the CGG repeat island in the FMR1 gene to between 55 and 200 repeats. Evidence suggests that as well as conferring risk for neurodegeneration, the premutation is also associated with increased risk for autistic traits and psychiatric symptoms. An emotional processing fMRI task was used to examine the response to a change in emotional arousal in 17 male carriers and 17 matched controls. A psychiatric symptom checklist (SCL-90-R), autism spectrum and empathy quotients (AQ and EQ), and the Ekman Faces Test were used to investigate clinical symptoms and emotional processing. Carriers exhibited significantly lower activation compared to controls at the bilateral superior parietal lobe, bilateral Brodmann Area (BA) 17 (V1), right intraparietal area and right BA18 (V2) when comparing high and low arousal conditions. Group by age analyses were not significant. Assessments revealed that carriers displayed significantly worse symptoms of psychiatric symptoms and higher levels of autistic traits, as well as impaired facial emotion recognition. No measurements revealed an association with age. Here, we show significantly altered emotional processing in carriers which display stability over age, suggesting that, unlike degenerative aspects, emotional symptoms may be consistent over the lifespan in carriers.

Keywords: ASD; BOLD; CGG repeat; FXTAS; Fragile X; SCL-90-R; fMRI.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Arousal / physiology*
  • Brain / diagnostic imaging*
  • Brain / physiopathology
  • Cross-Sectional Studies
  • Emotions / physiology*
  • Fragile X Mental Retardation Protein / genetics*
  • Heterozygote*
  • Humans
  • Magnetic Resonance Imaging / methods*
  • Male
  • Mental Disorders / diagnostic imaging
  • Mental Disorders / genetics
  • Mental Disorders / psychology
  • Middle Aged
  • Young Adult


  • FMR1 protein, human
  • Fragile X Mental Retardation Protein