(PS4-A23) Brain Volume Associations with Irritability Symptoms in Children

Background. Irritability, or an increased proneness to frustration and anger, is among the most common reasons that children and adolescents are brought in for psychiatric care and is associated with the emergence of anxiety and depression. However, few studies have examined the pathophysiology of irritability, including potential neurostructural risk factors. The purpose of the current study was to examine associations between regional gray matter volumes (GMV) and irritability in a large sample of children.

Methods. Participants included 9- to 10-year-old children (N = 9,755) from the Adolescent Brain Cognitive Development^SM Study (ABCD Study^®). A latent measure of irritability was derived using items from the Child Behavior Checklist, and we related this measure of irritability to 68 cortical and 19 subcortical gray matter volume regions using structural equation modeling. Covariates included age, sex, race/ethnicity, scanner model, family income, parent’s highest level of education, medication use, and total intracranial volume. Multiple comparisons were accounted for using the false discover rate (FDR).

Results. After controlling for covariates and correcting for multiple comparisons, irritability was associated with smaller brain volumes in a number of frontal, temporal, and parietal regions (FDR corrected p-values ≤ .05). Out of the regions examined, irritability was inversely associated with GMV in 11 cortical regions, but no subcortical regions. Notable regions include smaller GMV in the superior frontal gyrus, right rostral anterior cingulate, and fusiform gyrus.

Conclusions. There is a lack of research examining the neurostructural correlates of irritability in youth. Using rigorous analyses, here we demonstrate inverse associations in regions implicated in impulse control, emotion regulation, and recognition of emotional expressions. These findings support theories positing socioemotional deficits as a key feature of irritability and demonstrate that these neurostructural differences are apparent at an early age.