Neurodevelopment Under Stress: How Adversity Timing and Neural Maturation Contribute to Variability in Mental Health

Date of Award

Spring 1-1-2025

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Psychology

First Advisor

Gee, Dylan

Abstract

Exposure to adversity (i.e., stressful and traumatic experiences) during development is a potent predictor of increased risk for psychopathology. Indeed, approximately 30% of all mental health disorders in adulthood are linked to early adversity exposure. However, there is vast heterogeneity in mental health outcomes following adversity exposure. Delineating the neural mechanisms underlying this variability is critical for informing risk identification and optimizing interventions. One factor that may contribute to heterogeneity in neural correlates of adversity exposure as well as risk for psychopathology is the developmental timing of adversity exposure. Given dynamic changes across brain development, adversity may interact with the biological state of the developing brain at the time of exposure to shape outcomes. Across three studies, this dissertation leverages complementary methods to probe the role of adversity exposure in shaping neural and mental health outcomes. Specifically, we assessed how person-centered profiles of adversity exposure during specific developmental stages and neural activation when discriminating between threat and safety relate to anxiety symptoms (Study 1); how age of adversity exposure is linked with white matter tract connectivity among brain-wide tracts and how such patterns relate to post-traumatic stress symptoms (Study 2); and how exposure to adversity may shape subcortical-cortical structure-function coupling across development, and how variation in structure-function coupling relates to psychopathology (Study 3). In Study 1, we identified three latent profiles of adversity exposure and corticolimbic activation when discriminating threat and safety. A ‘resilient’ group, with strong prefrontal activation to safety and moderate levels of adversity exposure during middle childhood and adolescence, displayed the lowest levels of anxiety symptoms in adulthood. These findings raise the possibility that middle childhood may represent a period during which adversity has an outsized impact on the developing brain, potentially conferring both risk and resilience depending on context and frequency. In Study 2, we found that adversity exposure during preschool-age and middle childhood (ages 3-8) was linked with a divergent multivariate pattern of white matter tract integrity, such that greater adversity exposure during ages 3-8 was associated with increased connectivity of sensorimotor tracts and decreased connectivity of cortico-cortical and corticolimbic tracts in adulthood. Further, this multivariate pattern of divergent tract integrity was associated with post-traumatic stress symptoms, suggesting that brain-wide variation in connectivity following adversity exposure may underlie stress-related symptoms. In Study 3, we found that adversity exposure was negatively associated with structure-function coupling between the hippocampus and ventromedial prefrontal cortex (vmPFC) in a large sample of youth across development. Additionally, hippocampal-vmPFC structure-function coupling moderated the association between adversity exposure and transdiagnostic psychopathology, suggesting that individual differences in the degree to which functional connectivity is constrained by underlying structure in the hippocampal-vmPFC circuit may buffer or exacerbate the impact of adversity exposure on mental health in youth. By taking developmentally-informed approaches to studying how adversity relates to multimodal neural features and transdiagnostic symptomatology, this dissertation provides evidence that the age at which adversity occurs may be meaningfully associated with altered neurodevelopment across modalities as well as later mental health, and that adversity-related neural differences at both a circuit-specific and whole-brain level may shape individual variation in risk for and resilience against psychopathology.

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