Autism in Fragile X Syndrome; A Functional MRI Study of Facial Emotion-Processing

Abstract

Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability and autism spectrum disorder, and among those with fragile X syndrome, approximately 1/3rd meet a threshold for an autism spectrum disorder (ASD) diagnosis. Previous functional imaging studies of fragile X syndrome have typically focused on those with fragile X syndrome compared to either neurotypical or autism spectrum disorder control groups. Further, the majority of previous studies have tended to focus on those who are more intellectually able than is typical for fragile X syndrome. In this study, we examine the impact of autistic traits in individuals with fragile X syndrome on a paradigm looking at facial emotion processing. The study included 17 individuals with fragile X syndrome, of whom 10 met criteria for autism as measured by the Autism Diagnostic Observation Schedule (ADOS). Prior to the scan, participants rehearsed on a mock scanner to help acclimatize to the scanner environment and thus allow more severely affected individuals to participate. The task examined the blood-oxygen-level-dependent (BOLD) response to fearful and neutral faces taken from the Ekman faces series. Individuals in the autism group had a region of significantly reduced activity centered on the left superior temporal gyrus, compared to those with FXS alone, in response to the fearful faces. We suggest that autism in individuals with fragile X syndrome is associated with similar changes in the neurobiology of facial emotion processing as seen in idiopathic autism.

Keywords: autism; emotion-processing; fragile X syndrome; functional imaging.

Figure A1

CONSORT diagram of recruitment and scanning. FXSoc—Fragile X Society.

Figure 1

(a) Cluster of significantly greater brain activation in the non-autism group, compared to the autism group during the fearful faces versus baseline contrast. Region projected on the canonical single subject T1 image from SPM12. (b) Extracted Eigenvariate values in the two groups from the cluster shown in panel (a).

Figure 2

Cluster of activation significantly correlated with ADOS Calibrated Severity Score in the autism subgroup. Region projected on the canonical single subject T1 image from SPM12.

Figure 3

Scatter plot of the correlation between extracted Eigenvariate value and Calibrated Severity Score (CSS) from the cluster shown in Figure 2. The solid line shows the linear regression, with the dotted lines demarcating the 95% confidence bands.