Diverging Effects of Violence Exposure and Psychiatric Symptoms on Amygdala-Prefrontal Maturation during Childhood and Adolescence

Abstract

Violence exposure during childhood and adolescence is associated with increased prevalence and severity of psychopathology. Neurobiological correlates suggest that abnormal maturation of emotion-related brain circuitry, such as amygdala-prefrontal cortex (PFC), may underlie the development of psychiatric symptoms after exposure; however, it remains unclear how amygdala-PFC circuit maturation is related to psychiatric risk in the context of violence. This study analyzed individual differences in amygdala-PFC circuit maturity using data collected from the Philadelphia Neurodevelopmental Cohort (PNC; N=1,133 youth). Neurodevelopment models of amygdala-PFC resting-state functional connectivity were built using deep learning, trained to predict chronological age in typically developing youth (neither violence exposed nor having a psychiatric diagnosis). Using the brain age gap estimate (BrainAGE), an index of relative circuit maturation, patterns of atypical neurodevelopment were interrogated. Violence exposure was associated with delayed maturation of basolateral amygdala (BLA) - PFC circuits, driven by increased BLA - medial orbitofrontal cortex functional connectivity. Increased psychiatric symptoms, on the other hand, was associated with advanced maturation of BLA - PFC functional connectivity, driven by decreased BLA - dorsolateral PFC functional connectivity. Delayed frontoamygdala maturation after exposure to violence suggests atypical, yet adaptive, development of threat appraisal processes, potentially reflecting greater threat generalization characteristic of younger children. Advanced circuit maturation with increasing symptoms suggests divergent neurodevelopmental mechanisms underlying illness after emotion-circuits have adapted to adversity, exacerbated by pre-existing vulnerabilities to early maturation. Disentangling the effects of adversity and psychopathology on neurodevelopment is crucial for helping youth recover from violence and preventing illness from continuing into adulthood.