Prevalence and Predictors of Anxiety Disorders in Adolescent and Adult Males with Autism Spectrum Disorder and Fragile X Syndrome

Background:   Fragile X syndrome (FXS) is a monogenetic disorder characterized by abnormal social behavior and intellectual disability. FXS is also the most frequent inherited cause of autism spectrum disorder (ASD), which makes it an ideal model for studying ASD. Additionally, high rates of anxiety symptomatology have been reported in FXS (~90%) and ASD (~40%). Despite the high association of anxiety, few studies have examined predictive indicators of anxiety in FXS to those in ASD, or the trajectory of symptoms over time.

Objectives:   Since nearly 70% of males with FXS meet criteria for ASD with considerable overlap with ASD and anxiety features, disentangling the trajectory of these features in FXS is critical to direct targeted treatments and can contribute to the latent heterogeneity in ASD. The purpose of this study is to advance our understanding of the nature of anxiety disorders in adolescent males with FXS compared to those with ASD by examining the prevalence and predictors of anxiety disorders using multiple measures over time.

Methods:   Participants included males with FXS (n=30) or ASD (n=7) from 16 to 24 years of age from an ongoing longitudinal study (with 10 more ASD by IMFAR). Screening indices of anxiety preceded diagnostic determination a year later.  Screening measures included the ADAMS and the CBCL anxiety subscales. The Children’s Interview for Psychiatric Symptoms-Parent Version (P-ChIPS), a semi-structured interview with mothers, measured diagnosis of anxiety disorders including Specific and Social Phobias and Generalized Anxiety Disorder (GAD). The ADOS-2 documented autism severity and the Leiter-R measured nonverbal IQ.

Results:   In preliminary analyses, no group differences were evident for chronological age or autism severity (p >.05). The FXS group did have a lower nonverbal IQ (t(18)=-4.43), p<.01); but, it was unrelated to anxiety diagnostic categorization for both groups. Findings indicate that 63% of the FXS adolescents met criteria for at least one anxiety disorder compared with 29% in ASD. Across the FXS and ASD groups respectively, 31% versus 14% met for Specific Phobia, 17% versus 14% met for Social Phobia and 33% versus 14% met for GAD. Anxiety problems from the CBCL were significantly greater in males with ASD than those with FXS (t(8)=-2.56), p<.05). In logistic regression models, group (B=2.13-2.25, p<0.05) predicted presence of an anxiety disorder while taking previous anxiety problems into effect as captured by the CBCL or ADAMS. 

Conclusions: This study is somewhat consistent with previous work indicating high prevalence of anxiety disorders in FXS and ASD; however, our data indicate generally lower rates for both the presence and specific anxiety diagnoses across both groups. Our primary finding is greater anxiety behaviors in FXS than idiopathic ASD across general (any anxiety) and specific categories (Specific Phobia, GAD). We also report that early symptoms of anxiety on screening measures predicted the presence of an anxiety disorder a year later in ASD. This study is the first to document a tentative difference between anxiety symptoms and later diagnoses in ASD and FXS adolescent males, allowing for more targeted assessment and treatment of anxiety in these populations.