Infant Social Avoidance Predicts Autism but Not Anxiety in Fragile X Syndrome

Abstract

Objective: Autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and anxiety are three of the most common childhood psychiatric disorders. Early trajectories of social avoidance have been linked with these psychiatric disorders in previous studies, but it remains unclear how social avoidance differentially predicts comorbid disorders in a high-risk genetic subgroup. Here, we delineate the association between trajectories of social avoidance from infancy and subsequent ASD, ADHD, and anxiety outcomes at preschool in children with fragile X syndrome (FXS), a well-characterized single-gene disorder highly associated with social avoidance as well as elevated rates of ASD, ADHD, and anxiety. Method: Males with FXS ( n = 78) aged 4–62 months participated in a longitudinal study resulting in 201 assessments. The Social Avoidance Scale (SAS) documented socially avoidant behaviors from infancy in three domains—physical movement, facial expression, and eye contact during both the first minute and the last hour of an interaction. ASD, ADHD, and anxiety symptom outcomes at preschool were measured via parent-report questionnaires. Results: Increased social avoidance across infancy and preschool predicted elevated ASD symptom severity but reduced ADHD and anxiety symptom severity in males with FXS. Conclusion: ASD, ADHD, and anxiety symptoms relate inconsistently to social avoidance behaviors, providing new insight toward the debate of independence or overlap among these disorders in FXS and other disorders (i.e., ASD). The results suggest that the nuanced profile of the developmental and temporal aspects of social avoidance may inform more the accuracy of differential diagnoses of comorbid psychiatric disorders in FXS.

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

“…It is possible that the higher rate in our sample may reflect changes in diagnostic criteria and the DSM-5 conceptualizations of ASD as a wider spectrum of impairment with only two core domains. Given the frequent report that ~90% of children with FXS exhibit at least one ASD feature (Merenstein et al, 1996; Roberts et al, 2019), coupled with the greater spectrum of impairment inherent in the DSM-5, differences in our rate versus others may reflect our use of the DSM-5 for diagnostic determination which has been suggested in a recent study with adolescents and young adults with FXS (Abbeduto et al, 2019). It is also possible that the increase in prevalence of ASD in FXS is associated with the national increase in prevalence of nsASD (Christensen et al, 2019).…”

“…Thus, it is not clear if sensory impairments across infancy are associated with increased risk of ASD in FXS, and this is an area for future research. In terms of avoidant eye contact, our previous work has shown that avoidant eye contact during infancy does predict the severity of ASD features at preschool age using ASD features across a continuum rather than as a categorical outcome using diagnostic determination (Roberts et al, 2019). Thus, our finding that avoidant eye contact across infancy does not predict diagnoses of ASD in this study likely reflects reduced power associated with categorical outcomes and small samples.…”

“…The Social Avoidance Scale (SAS) eye contact subscale (Roberts et al, 2019; Roberts et al, 2019; Roberts, Weisenfeld, Hatton, Heath, & Kaufmann, 2007) was used to measure eye contact avoidance at the end of each assessment visit. For the rating, the research team observes and records the participant's response to their interactions across the final hour of interaction once that child has become familiar with them (details on reliability, validity, and procedure are in Roberts et al, 2019).…”

“…Social avoidance has also been documented in the first year of life in infants with FXS with a steady increase across early childhood (Roberts et al, 2019). Of note, elevated social avoidance across the infant and toddler years differentially predicted increased severity of ASD symptoms, but not ADHD or anxiety symptoms, at preschool age (Roberts et al, 2019).…”

Early negative affect in males and females with fragile X syndrome: implications for anxiety and autism

“…The current findings also contribute to the debate regarding the independence and overlap of symptoms of anxiety to ASD in FXS as elevated anxiety in FXS is often attributed as the cause of “misdiagnoses of ASD” [59]. Social avoidance and impaired eye contact are hallmark features of both anxiety and ASD in FXS, and these overlapping features are often misattributed as ASD symptoms without taking into account the contributions of anxiety [59, 60]. Our findings that trajectories of negative affect predicted anxiety and not ASD suggests that anxiety and ASD are indeed independent disorders with different risk factors.…”