Temperament As a Predictor of Anxiety in High-Risk Infants

Background: Fragile X syndrome (FXS) is a monogenetic disorder characterized by intellectual disability and is the leading known heritable genetic cause of autism spectrum disorder (ASD), which makes it an ideal model for studying ASD. High rates of anxiety have been reported in both FXS and ASD with features of anxiety and ASD overlapping. Specific infant temperament profiles characterized by elevated negative affect have been associated with later emerging anxiety in typically developing and FXS samples and may be predictive of later anxiety in ASD (Tonnsen et al 2013). Despite the high association of anxiety in these disorders, no studies have examined relationships of temperament to anxiety using a cross-syndrome approach. Understanding early features and the trajectory of anxiety symptoms is critical to direct early, targeted treatments to reduce or prevent the occurrence of anxiety in these populations.

Objectives: The purpose of this study is to characterize the emergence of anxiety disorders in high risk infant populations; infants with FXS or ASD siblings contrasted to low-risk controls with two primary questions:

1. What is the prevalence of anxiety symptoms in 24-month-olds with FXS, ASD siblings, and TD controls? 
2. Does negative affect at 12 months predict anxiety symptoms at 24-months in FXS contrasted to ASD siblings and low risk infants covarying for developmental level?

Methods: We used a prospective longitudinal design. Participants included 31 infants with FXS, 31 ASD siblings, and 37 low-risk controls. The Negative Affect cluster of the Rothbart-Infant Behavioral Questionnaire (IBQ), a parent measure of infant temperament, was completed at 12-months. The Child Behavior Checklist (CBCL) 1.5 – 5 years old Anxiety Problems Subscale, a DSM oriented scale of anxiety, was completed at 24 months. The Early Learning Composite (ELC) of the Mullen Scales of Early Learning, a measure of broad development, was completed at both age points.

Results: A one-way ANOVA showed that the CBCL Anxiety scores for the FXS group were significantly higher than both the ASD siblings (p=.006) and low risk controls (p=.004). A linear regression showed a significant main effect for group and Negative Affect predicting anxiety at 24 months when ELC is covaried (F(2, 62)=2.25, p=.049). Correlations for each group showed a moderate, positive relationship between Negative Affect and anxiety symptoms for infants with FXS (r(18) = .40, p=.086).

Conclusions: This is the first study to compare anxiety symptomatology across infants at high and low risk for anxiety and ASD. Further, this is also the first study to use temperament as a predictor of anxiety symptoms at 24 months of age. Results suggest that the FXS group has elevated anxiety symptomology strongly correlated with negative affect that is distinct from the ASIB group, which indicates potential etiologically distinct profiles of the relationship of early temperament to anxiety or ASD in high-risk groups. Temperament characterized by negative affect may impair infants’ responses to the environment, reducing positive interaction and resulting in greater emergence of anxiety.