Linking irritability and functional brain networks: A transdiagnostic case for expanding consideration of development and environment in RDoC

The National Institute of Mental Health Research Domain Criteria (RDoC) framework promotes the dimensional and transdiagnostic operationalization of psychopathology, but consideration of the neurodevelopmental foundations of mental health problems requires deeper examination. Irritability, the dispositional tendency to angry emotion that has both mood and behavioral elements, is dimensional, transdiagnostic, and observable early in life—a promising target for the identification of early neural indicators or risk factors for psychopathology. Here, we examine functional brain networks linked to irritability from preschool to adulthood and discuss how development and early experience may influence these neural substrates. Functional connectivity measured with fMRI varies according to irritability and indicates the atypical coordination of several functional networks involved in emotion generation, emotion perception, attention, internalization, and cognitive control. We lay out an agenda to improve our understanding and detection of atypical brain:behavior patterns through advances in the characterization of both functional networks and irritability as well as the consideration and operationalization of developmental and early life environmental influences on this pathway.