Caudate volume is prospectively associated with irritability in toddlerhood: A preliminary investigation

Irritability refers to the dispositional tendency to respond with anger and frustration to environmental challenges or limits, with both mood and behavioral elements. The dimensional spectrum of irritability is an RDoC-informed transdiagnostic marker of psychopathology risk, specifically for the common and modifiable internalizing and externalizing disorders. Despite substantial interest in this robust developmentally based transdiagnostic indicator of psychopathology risk, its early brain markers are understudied. Here, we leveraged high-quality, longitudinal behavioral phenotyping of irritability within an imaging substudy (n = 31) of toddlers, from the When to Worry (W2W) study. We examined prospective associations between volume in three subcortical regions implicated in irritability (the caudate, putamen, and amygdala) around the infants' first birthday (Baseline) and the dimensional spectrum of observed irritability using the Disruptive Behavior Diagnostic Observation Schedule (DB-DOS) around toddlers' second birthday (Follow-up). Both left (q = .04, FDR corrected) and right caudate volumes (q = .04, FDR corrected) at Baseline were negatively associated with observed irritability at Follow-up. We did not find support for associations between putamen and amygdala volumes at Baseline and observed irritability at Follow-up. These findings identify early prospective neuroanatomical correlates of toddler irritability and provide preliminary support for the caudate being one important brain region for further investigation regarding the early neural correlates of irritability.