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

Abstract

Anxiety disorders are the most prevalent disorders in children and adolescents, affecting approximately 15-20% of individuals under the age of 18 (Salum et al, 2013). Clinical subgroups, like autism spectrum disorder (ASD) and fragile X syndrome (FXS), have an elevated risk of a co-occurring anxiety disorder. Despite the elevated risk of anxiety in these groups, few research studies have investigated the rates and predictors of anxiety disorders in adolescents with these ASD and FXS. In the current study, participants included males with FXS (n=31) or ASD (n=20) aged 16 to 24. Measures included the Children's Interview for Psychiatric Symptoms-Parent Version (P-ChIPS), the Autism Diagnostic Observation Schedule-2 (ADOS-2), and the Leiter International Performance Scale-Revised (Leiter-R). Descriptive statistics indicated that 48% of the FXS adolescents met criteria for an anxiety disorder compared with 50% in ASD. Additionally, 13% of the FXS and 30% of the ASD sample met for multiple anxiety disorders. Across the FXS and ASD groups 35% versus 15% met for Specific Phobia, 12% versus 30% met for Social Phobia and 33% versus 40% met for GAD, respectively. T-tests showed no significant differences within and across groups for those meeting criteria for an anxiety disorder verses those not meeting criteria for age, NVIQ growth scores, and ASD severity. Results of the binary logistic regression did not show age, NVIQ growth scores, or ASD severity as significant predictors of any anxiety disorder across FXS and ASD. Lastly, approximately 40% of participants with FXS who met criteria for an anxiety disorder were prescribed medications for anxiety, as compared iv iv to 20% of the participants with ASD who met criteria for an anxiety disorder. Logistic regression results showed that taking anxiety medications were not significantly predictive of meeting criteria for an anxiety diagnosis however anxiety medication use was predictive of group diagnosis. Our primary finding is that approximately half of the FXS and ASD sample met for an anxiety disorder based on DSM-V criteria. Further, This study is the first that directly compares rates of anxiety disorders across adolescents and adults with FXS and idiopathic ASD within a small range of ages, intellectual ability, and autism severity. Reduced rates of anxiety disorders may be indicative of adolescent or young adult males with lower intellectual functioning who have FXS or ASD. v TABLE OF CONTENTS

Emergence and rate of autism in fragile X syndrome across the first years of life

“…GAD and separation anxiety disorder were also relatively uncommon across the groups with and without ASD (4% vs. 5% and 8% vs. 10% respectively). Consistent with the lower incidence of any anxiety disorder, our incidence of specific anxiety disorders is lower than studies published with older children and adults with FXS (Cordeiro et al, 2011; Ezell et al, 2019). However, two striking areas of consistency across the current and existing studies with older samples is that specific phobia is the most prevalent anxiety disorder, and ASD status or severity of symptoms is not clearly associated with differential rates of comorbid anxiety diagnoses in FXS.…”

“…However, our results reflect lower rates than reported in two studies of older individuals with FXS that included direct in-depth assessments of both anxiety and ASD. These studies report that 51.6% of males aged 16 to 24 years (Ezell et al, 2019) and 82.5% of males and females aged 5 to 26 years (Cordeiro, Ballinger, Hagerman, & Hessl, 2011) met diagnostic criteria for any anxiety disorder. The higher rate of anxiety disorders in the older FXS samples is consistent with the fact that anxiety disorders typically emerge in middle to late childhood and the severity of anxiety symptoms in FXS has been shown to increase with age (Cordeiro et al, 2011) as is the case with neurotypical individuals (Bosquet & Egeland, 2006; Copeland, Angold, Shanahan, & Costello, 2014).…”

Anxiety and threat‐related attentional biases in adolescents with fragile X syndrome

“…These decisions are consistent with previous work documenting independence of anxiety diagnoses from autism and cognitive features in an overlapping sample (Ezell et al . ).…”

“…; Ezell et al . ). Although elevated anxiety‐related features are well‐documented in FXS as early as infancy (Tonnsen et al .…”

“…Anxiety disorders constitute one of the most common and impairing comorbidities associated with fragile X syndrome (FXS), with the majority of males adolescents meeting diagnostic criteria (Cordeiro et al 2011;Ezell et al 2018). Although elevated anxiety-related features are well-documented in FXS as early as infancy (Tonnsen et al 2013(Tonnsen et al , 2017 Tonnsen and Roberts 2016) and intensify across development (Cordeiro et al 2011), measuring features of anxiety in FXS and other neurogenetic syndromes is inherently challenging due to common limitations in language, self-awareness and cognitive skills required for traditional assessment tasks.…”