Heterogeneity in the Neural Mechanisms of Adversity: Implications for Developmental Risk and Resilience

Abstract

The wide heterogeneity in adverse outcomes of stressful experiences unexplained in existing literature suggests that more research is needed to understand the developmental risk and resilience to adversity. Specifically, why and how do certain experiences lead to mental health problems for some but not others? What neural mechanisms could account for the long-term effects of adverse experiences on mental health? This dissertation addressed these questions using prospective longitudinal data from a population-based birth cohort sample. The findings demonstrate that the developmental impact of adversity is specific to the types of experiences and neural features, thus requiring approaches that can capture the complexities of both the environment and the brain. Study one examined the differential neural mechanisms implicated in the long-term neural and behavioral consequences of childhood adversity across 21 years. Results show that household instability during childhood was associated with structural brain network organization in adolescence, even after accounting for other types of adversities. Moreover, structural network organization indirectly explained the association between childhood instability and depressive symptoms in young adulthood, demonstrating the prolonged influence of the early environment on mental health through experience-specific neural correlates. In study two, data-driven person-specific functional connectivity subgroups in adolescence were identified to predict mental health outcomes and stress susceptibility six years later, during the highly stressful period of the global pandemic. Findings revealed that individuals with greater functional connectivity involving specific emotion-related key regions (amygdala, subgenual cingulate cortex, ventral striatum) showed an increased trajectory of anxiety symptoms and were more susceptible to future stress, relative to those with connectivity involving other brain regions (dorsal anterior cingulate cortex, insula). These findings suggest that the associations between adverse experiences and mental health differ based on specific emotion-linked neural regions. Finally, study three built upon the previous studies by addressing heterogeneity in childhood adversity as well as adolescent brain networks using person-oriented approaches. First, data-driven latent profiles were identified using adverse experiences across multiple contexts during the first nine years of life. These profiles were then used to estimate differences in prospective youth mental health outcomes and person-specific functional brain networks. Findings demonstrate that youth with a profile indicated by high exposure to multi-domain adversity, as well as those with an adversity profile characterized by exposure to high maternal depression, exhibited the highest levels of internalizing and externalizing symptoms in adolescence. These patterns were also reflected in the brain function of these youth during emotion processing; specifically, youth with the high-adversity and maternal depression profiles showed the highest density within the default mode network. Additionally, those with the high childhood adversity profile showed attenuated salience network density and greater frontoparietal network density, suggesting aberrant network communication in key emotion regulatory regions. Collectively, this dissertation provides empirical evidence that the neural mechanisms of adversity are specific to the types of experiences, the brain regions involved, and their contextual interactions, which underscore the importance of considering development as an individualized process to parse heterogeneity in the influence of adversity. This work informs future studies by integrating broader environmental measures in characterizing adversity and adopting novel approaches in modeling brain development across multiple levels of analysis.