Preschool- and School-Age Irritability Predict Reward-Related Brain Function

Objective: Although chronic irritability in childhood is prevalent, impairing, and predictive of later maladjustment, its pathophysiology is largely unknown. Deficits in reward processing are hypothesized to play a role in irritability. The current study aimed to identify how the developmental timing of irritability during preschool- and school-age relates to reward-related brain function during school-age. Method: Children's irritability was assessed during the preschool period (wave 1; ages 3.0-5.9 years) and 3 years later (wave 2; ages 5.9-9.6 years) using a clinical interview. At wave 2, children (N = 46; 28 female and 18 male) performed a monetary incentive delay task in which they received rewards, if they successfully hit a target, or no reward regardless of performance, during functional magnetic resonance imaging. Results: Children with more versus less severe preschool irritability, controlling for concurrent irritability, exhibited altered reward-related connectivity: right amygdala with insula and inferior parietal lobe as well as left ventral striatum with lingual gyrus, postcentral gyrus, superior parietal lobe, and culmen. Children with more versus less severe concurrent irritability, controlling for preschool irritability, exhibited a similar pattern of altered connectivity between left and right amygdalae and superior frontal gyrus and between left ventral striatum and precuneus and culmen. Neural differences associated with irritability were most evident between reward and no-reward conditions when participants missed the target. Conclusion: Preschool-age irritability and concurrent irritability were uniquely associated with aberrant patterns of reward-related connectivity, highlighting the importance of developmental timing of irritability for brain function.