Autism, Anxiety and the Role of Gene Expression in Female Children and Adolescents with Fragile X Syndrome

Thursday, May 11, 2017: 5:30 PM-7:00 PM
Golden Gate Ballroom (Marriott Marquis Hotel)
M. Chernenok1, J. L. Burris2 and S. Rivera3, (1)Department of Human Ecology, University of California, Davis, Davis, CA, (2)Department of Psychology, University of California, Davis, Davis, CA, (3)Department of Psychology, University of California at Davis, Davis, CA

Fragile X syndrome (FXS) is a genetic disorder caused by a trinucleotide CGG expansion within the fragile X mental retardation 1 (FMR1) gene located on the X chromosome. In boys this typically leads to methylation and silencing of the gene. In girls, however, there is variability in gene expression due to compensation by the normally-functioning X chromosome. This variability provides an important opportunity to evaluate the differential role of FMR1 gene expression in the phenotypic presentation of the syndrome. FXS is highly comorbid (25-60%) with autism spectrum disorder (ASD) and with anxiety disorders (86%). Given the known increased prevalence of anxiety in females in general, the current study aims to not only elucidate the anxiety profile of adolescent females with FXS, but to also investigate the impact of ASD on anxiety in this population.


The current study evaluated the anxiety profiles of female children and adolescents with FXS, with and without comorbid ASD. Moreover, we included females with the full mutation and with mosaicism, as both groups allow us to explore the variable role of FMR1 gene expression on anxiety.


Participants included 16 females with FXS, ages 9- 18, of which 8 had a comorbid ASD diagnosis. Allele status was confirmed by FMR1 DNA testing. Activation ratio (AR) was calculated to measure the percentage of cells with the normal allele on the active X chromosome, and provided us with an estimate of FMR1 of gene expression. Assessments included the Anxiety, Depression, and Mood Scale (ADAMS) used to evaluate anxiety, and the Autism Diagnostic Observation Schedule (ADOS) used to evaluate severity of autism symptomatology. An ANOVA was conducted to investigate the interaction between ADAMS, AR, and ASD diagnosis.


There was a significant main effect for autism diagnosis, F (1, 12) = 19.87, p = .001, such that girls with FXS who had an ASD diagnosis scored higher on the ADAMS (indicating increased severity) than those who did not. There was also a significant main effect for gene expression, F (1, 12) = 5.53, p = .037, and no diagnosis by gene expression interaction, indicating that individuals with decreased FMR1 gene activation scored higher on the ADAMS independent of ASD diagnosis.


These findings extend our knowledge about the role of autism and FMR1 gene expression in the severity of anxiety symptomatology present in adolescent girls with FXS. While prior work has focused on the prevalence of anxiety in the FXS phenotype, it has not, until now, examined the role of genetic variability in anxiety. Moreover, while ASD is also a clinically impactful component of the FXS phenotype, little to no work has linked ASD and anxiety directly to FXS. This study shows that not only do girls with FXS who have an ASD diagnosis have higher levels of anxiety, but that level of anxiety is directly impacted by the functioning of the FMR1 gene.