Abstract
The transdiagnostic importance of irritability in psychopathology has been demonstrated. However, the contribution of developmentally unfolding irritability patterns to specific clinical and neural outcomes remains an important and unanswered question. To address this gap in the literature, irritability patterns of 110 youth from a large, diverse cohort were assessed at preschool age and again at early school age (∼2.5 years later) with a dimensional irritability scale designed to capture the normal:abnormal spectrum. At preadolescence (∼6 years later), clinical outcomes (internalizing/externalizing symptoms) derived from a semistructured clinical interview and neural outcomes (characterized as gray-matter-volume abnormalities) were assessed. For clinical outcomes, preschool-age irritability alone was a transdiagnostic predictor of internalizing and externalizing symptoms at preadolescence. However, in a model including both preschool and early school age, irritability provided greater specificity, suggesting that higher irritability at early school age related to elevated preadolescent externalizing but not internalizing symptoms. In terms of neural outcomes, elevated preschool irritability did not predict preadolescent gray-matter-volume abnormality; however, irritability at early school age demonstrated an interactive effect among regions, with reduced volume in preadolescence emotional regions (e.g., amygdala, medial orbitofrontal cortex) and increased volume in other regions (e.g., cerebellum). These complex patterns highlight the contribution of a developmentally informed approach, the National Institute of Mental Health's Research Domain Criteria (RDoC) approach, to yield transdiagnostic phenotypes and multiple units of analysis. Capturing these individual differences and developmental heterogeneity can provide critical insight into the unfolding of mechanisms underlying emerging psychopathology. (PsycInfo Database Record (c) 2022 APA, all rights reserved).