Developmental Patterning of Irritability Enhances Prediction of Psychopathology in Pre-adolescence: Improving RDoC with Developmental Science

Abstract

Research has demonstrated the transdiagnostic importance of irritability in psychopathology pathways but the contribution of developmentally-unfolding patterns has only recently been explored. To address this question, irritability patterns of 110 youth from a large and diverse early childhood cohort were assessed at preschool age and at school age (~2.5 years later) with a dimensional irritability scale designed to capture the normal:abnormal spectrum.Participants then returned at Pre-adolescence (~6 years later) for an assessment with a structured clinical interview (internalizing/externalizing symptoms) and a magnetic resonance imaging scan. When only preschool age irritability was considered, this was a transdiagnostic predictor of internalizing and externalizing symptoms. However, a model including both preschool and school age irritability provided a more nuanced picture. A high preschool and decreasing school age profile of irritability predicted elevated pre-adolescence internalizing symptoms, potentially reflecting emerging coping/internalizing behavior in pre-adolescence. In contrast, a stable irritability profile across these timepoints predicted increased pre-adolescence externalizing symptoms. Further, preschool irritability (a period of rapid growth) did not predict preadolescent gray matter volume abnormality, an indicator of transdiagnostic clinical risk.However, irritability at school age (when gray matter volume growth is largely finished) demonstrated an interactive effect among regions; increased school age irritability predicted reduced volume in pre-adolescence emotional regions (e.g., amygdala, medial orbitofrontal cortex) and increased volume in other regions (e.g., cerebellum). Expanding the impact of RDoC's approach yielding transdiagnostic phenotypes and multiple units of analysis, a developmentally informed approach provides critical new insights into the complex unfolding of mechanisms underlying emerging psychopathology. IRRITABILITY PREDITS CLINICAL OUTCOMES/GRAY MATTER VOLUMES

The centrality of temperament to the research domain criteria (RDoC): The earliest building blocks of psychopathology

“…In other words, children with high and stable levels of irritability in preschool (M age = 4.17 years) and elementary school (M age = 6.95 years) were reported to show more externalizing behavior in pre-adolescence. In contrast, children with high but decreasing levels of irritability across these time points displayed more internalizing behavior in pre-adolescence (Damme et al, 2021). Together, these findings suggest that clinical prediction may be improved when the developmental course of irritability is taken into consideration.…”

“…Importantly, the type, frequency, and intensity of the behaviors tend to manifest differently over the first 5 years of life, both within and between individuals (e.g., Denham, Lehman, & Moser, 1995;Eisenberg et al, 1997;Liu et al, 2018). Capturing these variations may help to identify patterns associated with later psychopathology (e.g., Damme, Wakschlag, Briggs-Gowan, Norton, & Mittal, 2021). Using a person-centered approach, Perra, Paine, and Hay (2020) found that, from 6 to 36 months of age, three subgroups of infants could be identified based on their levels of anger/aggressiveness.…”

“…Importantly, high levels of irritability in early life underpin multiple psychological disorders, including disruptive mood dysregulation disorder, oppositional defiant disorder, and attention deficit/hyperactivity disorder . Recent findings from Damme and colleagues (Damme et al, 2021) suggest that the course of irritability over early development may also influence manifest psychopathology in late childhood. In other words, children with high and stable levels of irritability in preschool (M age = 4.17 years) and elementary school (M age = 6.95 years) were reported to show more externalizing behavior in pre-adolescence.…”

Translating RDoC to real-world impact in developmental psychopathology: A neurodevelopmental framework for application of mental health risk calculators

“…Risk calculators predicting depression and ADHD in youth and young adults have also been tested, demonstrating c statistics above 0.7 in test samples (but poorer discrimination in some validation samples; e.g., Caye et al, 2020;Rocha et al, 2021). Research has also shown that some of the problem behaviors identified in these older age groups (e.g., the majority of severe and chronic internalizing and externalizing problems; Meehan et al, 2020;Damme, Wakschlag, Briggs-Gowan, Norton, & Mittal, 2021) onset with symptoms or vulnerability patterns in early childhood, laying the groundwork for identification far earlier in the developmental sequence (Wakschlag et al, 2018).…”

ERP Mismatch Negativity Amplitude and Asymmetry Reflect Phonological and Rapid Automatized Naming Skills in English-Speaking Kindergartners

“…Studying these specific skills that have a strong relation with reading may provide greater mechanistic insight because they are more focused and dimensional than the general diagnostic category of dyslexia or grouping based on word reading scores. Researchers and leaders in the area of mental health have advanced a dimensional, symptoms-based approach (National Institute of Mental Health's Research Domain Criteria, or RDoC; Cuthbert and Insel, 2013) in order to parse heterogeneity in diagnostic categories, which are particularly varied in development (Mittal and Wakschlag, 2017;Damme et al, 2020) and ultimately, to better understand the neurobiology of disorders. Thus, in this study, we explicitly tested how MMN measures related to PA and RAN, two crucial reading-related skills and deficits in dyslexia.…”