Parsing neurodevelopmental features of irritability and anxiety: Replication and validation of a latent variable approach

Abstract

Irritability and anxiety are two common clinical phenotypes that involve high-arousal negative affect states (anger and fear), and that frequently co-occur. Elucidating how these two forms of emotion dysregulation relate to perturbed neurodevelopment may benefit from alternate phenotyping strategies. One such strategy applies a bifactor latent variable approach that can parse shared versus unique mechanisms of these two phenotypes. Here, we aim to replicate and extend this approach and examine associations with neural structure in a large transdiagnostic sample of youth (N = 331; M = 13.57, SD = 2.69 years old; 45.92% male). FreeSurfer was used to extract cortical thickness, cortical surface area, and subcortical volume. The current findings replicated the bifactor model and demonstrate measurement invariance as a function of youth age and sex. There were no associations of youth's factor scores with cortical thickness, surface area, or subcortical volume. However, we found strong convergent and divergent validity between parent-reported irritability and anxiety factors with clinician-rated symptoms and impairment. A general negative affectivity factor was robustly associated with overall functional impairment across symptom domains. Together, these results support the utility of the bifactor model as an alternative phenotyping strategy for irritability and anxiety, which may aid in the development of targeted treatments.

Trial registration: ClinicalTrials.gov NCT02531893 NCT00025935 NCT00006177 NCT00018057.

Keywords: anxiety; bifactor model; cortical structure; irritability; subcortical volume.

Figures

Figure 1.

(a) Initial bifactor model including only one unique irritability factor and (b) best fit bifactor model with unique factors of parent-reported irritability, youth-reported irritability, and anxiety, as well as a common factor of negative affectivity. Each path includes the factor loadings for each observed variable on each latent variable. ARI, Affective Reactivity Index. It, item. SCARED, Screen for Child Anxiety Related Emotional Disorders. Gen, generalized anxiety disorder subscale. Pan, panic disorder subscale. Sch, school avoidance subscale. Sep, separation anxiety disorder subscale. Soc, social anxiety disorder subscale. Y, youth report. P, parent report. ***p < .001.

Figure 2.

Unstandardized factor loadings resulting from weak factorial model analyses of the effects of (a) sex and (b) gender. *Indicate loadings that when freed resulted in nonsignificant chi-square difference test between configural and weak factorial models.

Figure 3.

Conditional effect of the relationship between parent-reported irritability factor scores and clinician-rated temper outbursts across values of the moderator, age. Error bars represent the 95% confidence intervals. *p < .05.

Figure 4.

(a) Histogram of factor loadings across diagnostic groups and (b) average standardized factor loadings for each of the four latent factors across the four diagnostic groups: disruptive mood dysregulation disorder (DMDD), anxiety disorder (ANX), attention-deficit/hyperactivity disorder (ADHD), and no psychiatric disorder (HV). *Bonferonni-corrected p < .05.