Social Anxiety Traits Overlap Between Fragile X Syndrome, Autism Spectrum Disorder

Vijaya Iyer, PhD avatar

by Vijaya Iyer, PhD |

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Social anxiety and autistic traits are prevalent in males with fragile X syndrome and these behaviors overlap with those observed in individuals with autism spectrum disorder (ASD) without a known genetic syndrome, a study reports.

The overlap of traits between the two clinical subgroups makes their measurement extremely challenging, researchers said.

The study, “Biobehavioral composite of social aspects of anxiety in young adults with fragile X syndrome contrasted to autism spectrum disorder,” was published in the American Journal of Medical Genetics.

Anxiety, especially social anxiety  — fear or discomfort when interacting in a social setting — is prevalent in males with fragile X syndrome (FXS), with approximately 86% meeting diagnostic criteria for an anxiety disorder, and more likely have subclinical symptoms.

A high prevalence of anxiety disorders has also been reported in individuals with nonsyndromic ASD  — without a known genetic syndrome, as in FXS  — with 40% to 60% of youth meeting diagnostic criteria for an anxiety disorder and up to 37% diagnosed with social anxiety disorder.

However, the associations of social anxiety with intellectual disability severity, ASD symptom severity, and chronological age are not well-established in FXS.

Similarly, there is a need to differentiate between the anxious behavior observed in patients with ASD compared to those with FXS.

Researchers conducted a behavioral and biological assessment in patients with FXS and compared the data with ASD patients. Data were collected as part of a larger longitudinal, multi-site study focused on language as one of several predictors of successful transition into adulthood performed at the University of California, Davis MIND Institute and at the University of South Carolina.

The study included 77 adolescent and adult males ages 15-23. Of the 77 participants, 59 were FXS patients; 18 were nonsyndromic ASD patients.

The full mutation of the FMR1 gene was confirmed for the participants in the FXS group and ruled out in the nonsyndromic ASD group by reviewing records documenting molecular genetic testing prior to study participation.

Autism diagnostic observation schedule-2 (ADOS-2) was used for the diagnosis of ASD. This test is a standardized assessment of communication, social interaction, play, and restricted and repetitive behaviors that diagnoses ASDs across age, developmental level, and language skills.

Of the 59 FXS patients, researchers subdivided the group with FXS into those with ASD (44 patients) and those without ASD (15 patients).

Researchers then used multiple assessment questionnaires and indexes to evaluate anxiety predictors and social avoidance scale (SAS) to measure behavior of social avoidance.

A 113-item questionnaire — Child behavior checklist (CBCL) — was completed by caregivers (parents) and reflected the emotion and behavior of children ages 6-18.

Similarly, caregivers also completed a 23-item report called the anxiety depression and mood scale (ADAMS) that measured depressed mood, obsessive/compulsive behavior, social avoidance, hyperactivity, and general anxiety.

The nonverbal intellectual ability of patients was measured using the Leiter International Performance Scale-Revised (Leiter-R), a battery of individually administered tests to assess cognitive functions in children and adolescents.

Assessments were conducted over two consecutive days. The first day included assessments of language and cognition; the second day consisted of measures of ASD and parent interviews in a standardized order.

Saliva samples were also collected from patients within 15 minutes of their arrival at the test centers and just before the beginning of the assessment to test for levels of cortisol. Elevated levels of this hormone are indicative of anxiety and stress.

The results revealed that baseline cortisol levels were not indicative of any difference in social anxiety status between the two groups. In line with previous data, the correlation between FXS and cortisol remained unclear.

By combining SAS, CBCL, Leiter-R and ADAMS scores — called a composite approach — a significant difference in social anxiety could be observed between FXS and ASD patients: the ASD group scored markedly higher compared to the FXS group in this multivariate analysis, indicating a highly significant mean anxiety score for patients with ASD.

These group differences were primarily driven by the SAS and ADAMS Social Anxiety measures, researchers observed.

However, when grouping FXS patients as with or without ASD, the anxiety symptom scales did not reveal any statistical difference.

“These findings align with both theoretical model and empirical data supporting the notion that representing complex traits, such as social anxiety, is best accomplished by employing multiple indicators,” the authors said.

Also, FXS without ASD patients could not be differentiated from the two groups with ASD by using the composite approach, but they could at an “individual measure level for traits of social avoidance and social anxiety,” the team noted.

“Collectively, our results suggest that anxiety and ASD symptoms are closely related in complex ways in these groups and that the measures employed in this study may lack sufficient discrimination or may differ across groups,” the authors wrote.

“We conclude that measuring anxiety and autism traits in fragile X syndrome and autism spectrum disorder is complex with features that overlap and interact in a dynamic manner,” they concluded.