Left amygdala structure mediates longitudinal associations between exposure to threat and long‐term psychiatric symptomatology in youth

Abstract

Traumatic experiences during childhood can have profound effects on stress sensitive brain structures (e.g., amygdala and hippocampus) and the emergence of psychiatric symptoms. Recent theoretical and empirical work has delineated dimensions of trauma (i.e., threat and deprivation) as having distinct neural and behavioral effects, although there are few longitudinal examinations. A sample of 243 children and adolescents were followed for three time points, with each assessment approximately 1 year apart (ages 9–15 years at Time 1; 120 males). Participants or their caregiver reported on youths' threat exposure, perceived stress (Time 1), underwent a T1‐weighted structural high‐resolution MRI scan (Time 2), and documented their subsequent psychiatric symptoms later in development (Time 3). The primary findings indicate that left amygdala volume, in particular, mediated the longitudinal association between threat exposure and subsequent internalizing and externalizing symptomatology. Greater threat exposure related to reduced left amygdala volume, which in turn differentially predicted internalizing and externalizing symptoms. Decreased bilateral hippocampal volume was related to subsequently elevated internalizing symptoms. These findings suggest that the left amygdala is highly threat‐sensitive and that stress‐related alterations may partially explain elevated psychopathology in stress‐exposed adolescents. Uncovering potential subclinical and/or preclinical predictive biomarkers is essential to understanding the emergence, progression, and eventual targeted treatment of psychopathology following trauma exposure.

Genetic Insights into Externalizing and Internalizing Traits through Integration of the Research Domain Criteria and Hierarchical Taxonomy of Psychopathology

“…Reduced left amygdala volume has been shown to mediate the relation between childhood threat exposure and the development of externalizing and internalizing symptoms. 86 Similarly, reduced left subcallosal cortical volume is a potential mediator of associations between personality and various emotional states (e.g., subjective well-being) and psychiatric disorders (e.g., alcohol dependence). 87 Psychopathology liability was also related to alterations in the organization and microstructure of white matter fibers, reflected by changes in orientation dispersion indices, which may signify disruptions in neural communication that contribute to various manifestations of psychopathology.…”