Using a Developmental Approach to Investigate Behavioral, Neurodevelopmental, and Depressive Irritability Types

ABSTRACTObjective Irritability is highly heterogeneous and a common challenge in youth clinical services. Although transdiagnostic, diagnostic manuals conceptualize severe irritability differently: the ICD-11 primarily recognizes it as behavioral (oppositional defiant disorder specifier), and the DSM-5-TR, as depressive (core to disruptive mood dysregulation disorder). Irritability is also highly prevalent in, and genetically-linked to neurodevelopmental conditions. It is unclear if irritability represents a unitary construct or multiple different types. We examined whether distinct behavioral, neurodevelopmental and depressive irritability types, differentiated by their developmental course, sex-preponderance, clinical, genetic, and environmental covariates, could be observed. Method Using data from the Avon Longitudinal Study of Parents and Children (female participants: 5,085; male participants: 5,028), we explored sex-stratified irritability latent profiles across five time-points (∼ages 7-25) for irritability measured with the Development and Well-Being Assessment. We investigated associations with various clinical, genetic, and environmental covariates typifying behavioral, neurodevelopmental and depressive conditions. Results We identified five irritability profiles similar across sexes (low, child-limited, child/adolescent-limited moderate, child/adolescent-limited high, high-stable) and two sex-specific profiles: adolescent-onset (female participants), fluctuating (male participants). Although most profiles were not distinguished by condition-specific covariates, two showed some specificity with neurodevelopmental or depressive conditions: (a) the male high-stable profile was associated with ADHD diagnosis and genetic liability, and autism-like traits (b) the female adolescent-onset profile was associated with depression diagnosis and genetic liability, and adolescent/adult stressful life events. Conclusion Irritability appears developmentally-heterogeneous. While often transdiagnostic, for some irritability may align with neurodevelopmental or depressive conditions. This could have potential implications for classification and treatment.