Neural mechanisms of reward processing in preadolescent irritability: Insights from the ABCD study

J Affect Disord. 2024 Oct 31:370:286-298. doi: 10.1016/j.jad.2024.10.124. Online ahead of print.

Abstract

Elevated youth irritability is characterized by increased proneness to frustration relative to peers when rewards are blocked, and is a transdiagnostic symptom that predicts multiple forms of psychopathology and poorer socioeconomic outcomes in adulthood. Although mechanistic models propose that irritability is the result of aberrant reward-related brain function, youth irritability as it relates to multiple components of reward processes, including reward anticipation, gain, and loss, has yet to be examined in large, population-based samples. Data from the Adolescent Brain and Cognitive Development (ABCD) baseline sample (N = 5923) was used to examine associations between youth irritability (measured by parent-report) and reward-related brain activation and connectivity in a large, preadolescent sample. Preadolescents (M age = 9.96 years, SD = 0.63) performed the Monetary Incentive Delay task during functional MRI acquisition. In the task, during the anticipation period, participants were informed of the upcoming trial type (win money, lose money, no money at stake) and waited to hit a target; during the feedback period, participants were informed of their success. Whole brain and region of interest (ROI) analyses evaluated task conditions in relation to irritability level. Preadolescents with higher compared to lower levels of irritability demonstrated blunted prefrontal cortex activation in the anticipation period and exaggerated striatum-prefrontal connectivity differences among reward conditions during the feedback period. These effects persisted after adjusting for co-occurring anxiety, depression, and attention-deficit/hyperactivity disorder symptoms. These findings provide evidence for the role of reward salience in pathophysiological models of youth irritability, suggesting a mechanism that may contribute to exaggerated behavioral responses.

Keywords: Brain; Irritability; Preadolescence; Psychopathology; Reward.