Internalizing symptoms in adolescence: understanding the roles of negative life events, emotion regulation, and the brain over time

The National Institute of Mental Health awarded Oregon Health & Science University $164,190 on December 19, 2025, under the Mental Health Research Grants program (CFDA 93.242) to fund a longitudinal study examining internalizing symptoms in adolescence through the lens of negative life events, emotion regulation dysfunction, and neurobiological mechanisms, with performance through July 31, 2029, at the Portland, Oregon campus.

The research addresses the elevated prevalence and high comorbidity of depression and anxiety symptoms during adolescence, with particular focus on understanding how negative life events exacerbate emotion dysregulation and increase risk for internalizing disorders. The study investigates whether changes in neural functioning—specifically alterations in resting-state functional connectivity of brain networks governing emotion-related cognition and disruptions in prefrontal cortex and amygdala development—provide explanatory power for the relationship between negative life events and internalizing problems, and whether neurobiological mediation persists over time. The work seeks to identify brain biomarkers of transdiagnostic features shared across depression and anxiety diagnoses to inform neurobiology-based early interventions during adolescence, when sustained neuroplasticity offers potential to improve treatment response and minimize long-term harm.

Abstract

Symptoms of depression and anxiety demonstrate a substantial increase in prevalence during adolescence and high estimated comorbidity. The consequences of adolescent-onset internalizing disorder symptoms are considerable, including an increased risk of suicide, which is already a leading cause of death for youth. Given modest remission rates and treatment responses for both depressive and anxiety disorders, interventions based on neurobiology and behavior during adolescence, a critical period of sustained neuroplasticity, may improve early intervention efforts and minimize long-term harm. Research has aimed to elucidate adolescent-emergent internalizing disorders by identifying brain biomarkers of transdiagnostic features, due to the overlap of many depression- and anxiety-related psychiatric diagnoses. Dysfunctional emotion regulation (ER) is one such shared feature, and literature has shown IT is exacerbated by negative life events (nles), life changes that are challenging (but not necessarily traumatic), particularly during adolescence when emotional reactivity is elevated. Nles are thought to promote emotion dysregulation and risk for internalizing disorders via prefrontal cortex and amygdala development and connectivity disruption. Stress (broadly defined), internalizing pathology, and ER dysfunction have also been linked to perturbations in resting state functional connectivity (rsfc) of brain networks governing emotion-related higher-order cognition. While self-reported ER dysfunction has been shown to partially mediate the nles-internalizing problem association in youth, more well-powered work is needed to understand underlying neurobiological mechanisms, including whether changes in neural functioning provide explanatory power and if neurobiological mediation persists over time. The goal of this study is to investigate the extent to which ER trajectories, behaviorally and neurobiologically, mediate the relationship between nles and changes in internalizing symptoms, while accounting for social risk and protective factors, in the large, diverse adolescent brain cognitive development (abcd) study sample. Based on preliminary analyses, i hypothesize that the trajectory of ER behavior and associated brain functioning will (1) at least partly mediate the positive association between nles and internalizing symptoms over time; and (2) this mediation will be stronger for those with low social support. Thus, this proposal aims to examine the trajectories of: (1) ER behavior, (2) neural correlates of emotion-influenced cognition (as measured by emotional n-back task fmri), and (3) rsfc of emotion- and higher-order cognition-related brain networks as mediators of the link between nles and internalizing symptoms across early adolescence, while evaluating social supports as moderators. Results from this proposal may help to provide insights for more personalized treatments based on neurobiology, behavior, and social context. Additionally, the robust and interdisciplinary training plan within a prominent academic medical and research institution proposed in this application will allow me to establish a strong foundation for a career as an academic physician-scientist at the intersection of psychiatry and translational neuroscience.