Associations among negative life events, changes in cortico-limbic connectivity, and psychopathology in the ABCD Study

Abstract

Adversity exposure is a risk factor for psychopathology, which most frequently onsets during adolescence, and prior research has demonstrated that alterations in cortico-limbic connectivity may account in part for this association. In a sample of youth from the Adolescent Brain Cognitive Development (ABCD) Study (N = 4006), we tested a longitudinal structural equation model to examine the indirect effect of adversity exposure (negative life events) on later psychopathology via changes in cortico-limbic resting-state functional connectivity (rsFC). We also examined the potential protective effects of parental acceptance. Generally, cortico-limbic connectivity became more strongly negative between baseline and year 2 follow-up, suggesting that stronger negative correlations within these cortico-limbic networks may reflect a more mature phenotype. Exposure to a greater number of negative life events was associated with stronger negative cortico-limbic rsFC which, in turn, was associated with lower internalizing (but not externalizing) symptoms. The indirect effect of negative life events on internalizing symptoms via cortico-limbic rsFC was significant. Parental acceptance did not moderate the association between negative life events and rsFC. Our findings highlight how stressful childhood experiences may accelerate neurobiological maturation in specific cortico-limbic connections, potentially reflecting an adaptive process that protects against internalizing problems in the context of adversity.

Does pubertal stage mediate the association between family environment and structure and function of the amygdala-mPFC circuit? A replication study of the longitudinal ABCD cohort

“…Specifically, family environment was associated with decreased amygdala-cingulo-opercular network functional (used proxy for amygdala-mPFC functional connectivity), increased ACC fractional anisotropy (FA) and decreased ACC cortical thickness via pubertal stage. As FA increases and thickness decreases over adolescence ( Lebel and Deoni, 2018 , Vijayakumar et al, 2016 , Walhovd et al, 2016 ), and as Brieant et al (2021) show that amygdala-CON functional connectivity decreased between wave 1 and wave 2 of the ABCD study, these findings suggest that accelerated pubertal development in response to early family stress may accelerate development of the amygdala-mPFC circuit. Replication of these initial results would further substantiate that accelerated pubertal development may affect and possibly accelerate neural development.…”

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

“…It is worth noting that this laterality finding is, to some extent, supported by previous work showing that threat‐exposed children exhibit greater anticorrelated functional connectivity between the left (not the right) amygdala and ventromedial prefrontal cortex and medial orbitofrontal connectivity, which was related to greater externalizing and internalizing symptomatology, respectively (Peverill et al, 2019 ). Findings from the ABCD youth study have also suggested differential associations between negative life events and connectivity trajectories for left and right amygdala, such that a greater number of stressful events is related to weaker positive connectivity between the left amygdala and the cingulo‐opercular network, which in turn predicted reduced internalizing symptomology (Brieant et al, 2021 ). Conversely, more stressful events were related to greater negative connectivity between the right amygdala and cingulo‐opercular network, which predicted reduced internalizing symptomology.…”

An epigenetic mechanism for differential maturation of amygdala-prefrontal connectivity in childhood socio-emotional development

“…Similarly, functional connectivity between amygdala and mPFC during emotional tasks shifts from positive functional coupling in childhood to negative functional coupling in adolescence, which more closely fits the mature top-down regulatory profile proposed for the circuit in adults with negative functional connectivity 8 . However, the strength and valence of amygdala-prefrontal coupling during resting-state paradigms is less consistent, with some studies reporting an increase in amygdala-mPFC coupling with age 7,15 and others reporting a decrease in amygdala-mPFC coupling with age 16,17 . Discrepancies in these findings may be due to localization specificity of mPFC regions, but nonetheless, prior research indicates an acute shift in amygdala-mPFC connectivity occurs between childhood, adolescence, and young adulthood.…”

“…While most prior work has focused on deficit models, attention should also be paid to the stressadapted skills developed in harsh environments 31 . Accelerated maturation of this neural circuitry is usually adaptive at the time and can lead to a reduction in anxiety 19 , and while internalizing symptoms may appear in the short-term 16 , they may facilitate resilience later in life 32 .…”