Early-Life Exposure to Violence and Fronto-Amygdala Circuit Maturation: Developmental Markers of Psychiatric Risk

• Main Author: Keding, Taylor J
• Format: Dissertation
• Language: English
• Published: ProQuest Dissertations & Theses 01-01-2021
• Subjects: Clinical psychology; Developmental biology; Neurosciences
• ISBN: 9798582576907

Exposure to violence (e.g., physical and sexual abuse, witnessing violence) during childhood is associated with increased prevalence and severity of pediatric psychopathology. Associated neurobiological correlates suggest that abnormal maturation of emotion-related brain circuits, such as amygdala-prefrontal cortex (PFC), may underlie the development of psychiatric symptoms after exposure. It remains unclear how amygdala-PFC circuit development is altered by violence and how atypical maturation is related to psychiatric risk. This dissertation used normative modeling techniques to analyze individual differences in amygdala-PFC circuit maturity. Using data collected from the Philadelphia Neurodevelopmental Cohort (PNC), normative neurodevelopment models of fronto-amygdala resting-state functional connectivity were built using deep learning, trained to predict chronological age in typically developing youth (neither violence exposure nor diagnosable psychopathology). Using the brain age gap estimate (BrainAGE), an index of circuit maturation, patterns of advanced and delayed development were interrogated. Feature importance in PFC regions driving atypical maturation patterns was analyzed using the Shapley value, a game-theoretic credit allocation metric. Violence exposure was associated with delayed maturation of basolateral amygdala (BLA) – PFC circuits, driven by increased BLA – medial orbitofrontal cortex functional connectivity, a circuit crucial for extinction learning of threat-related stimuli. Increased psychiatric risk, on the other hand, was associated with advanced maturation of BLA – PFC functional connectivity, driven by decreased BLA – dorsolateral PFC functional connectivity, a circuit crucial for explicit emotion regulation and the expression of psychopathology symptoms. Finally, the relationship between BLA – PFC maturation and externalizing symptom expression was moderated by violence exposure, where externalizing-resilient and -susceptible youth showed delayed and advanced maturation respectively. Overall, delayed fronto-amygdala maturation after exposure to violence suggests abnormal development of threat appraisal processes, potentially reflecting greater threat generalization and reduced extinction learning (more characteristic of younger children). Increased psychiatric risk related to advanced circuit development suggests that the development of psychiatric symptoms may itself be a unique form of adversity, exacerbated by pre-existing vulnerabilities that predispose fronto-amygdala circuits to early maturation. Clinical translation of normative neurodevelopment models may be of tremendous value to pediatric health professionals in monitoring healthy brain development and helping youth recover from violent traumas by decreasing psychiatric risk into adulthood.