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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. Highlights • Childhood adversity shapes cortico-limbic connectivity and mental health.• In the ABCD Study, cortico-limbic functional connectivity changed over time.• These changes explain the association between adversity and internalizing symptoms.• Adversity exposure may accelerate corticolimbic development.

SUBMITTER: Brieant A

PROVIDER: S-EPMC8556598 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Major depressive disorder (MDD) is a stress-related condition hypothesized to involve aberrant reinforcement learning (RL) with positive and negative stimuli. The present study investigated whether repeated early maternal separation (REMS) stress, a procedure widely recognized to cause depression-like behaviour, affects how subjects learn from positive and negative feedback. The REMS procedure was implemented by separating male and female rats from their dam for 6 h each day from post-natal day 5-19. Control rat offspring were left undisturbed during this period. Rats were tested as adults for behavioral flexibility and feedback sensitivity on a probabilistic reversal learning task. A computational approach based on RL theory was used to derive latent behavioral variables related to reward learning and flexibility. To assess underlying brain substrates, a seed-based functional MRI connectivity analysis was applied both before and after an additional adulthood stressor in control and REMS rats. Female but not male rats exposed to REMS stress showed increased response 'stickiness' (repeated responses regardless of reward outcome). Following repeated adulthood stress, reduced functional connectivity from the basolateral amygdala (BLA) to the dorsolateral striatum (DLS), cingulate cortex (Cg), and anterior insula (AI) cortex was observed in females. By contrast, control male rats exposed to the second stressor showed impaired learning from negative feedback (i.e., non-reward) and reduced functional connectivity from the BLA to the DLS and AI compared to maternally separated males. RL in male rats exposed to REMS was unaffected. The fMRI data further revealed that connectivity between the mOFC and other prefrontal cortical and subcortical structures was positively correlated with response 'stickiness'. These findings reveal differences in how females and males respond to early life adversity and subsequent stress. These effects may be mediated by functional divergence in resting-state connectivity between the basolateral amygdala and fronto-striatal brain regions.

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

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