Corticolimbic Structure–Function Coupling Is Sensitive to Childhood Adversity and Buffers Adversity-Related Symptoms during Development

Abstract

Childhood adversity is a potent predictor of mental health problems across the lifespan, and cross-species literature implicates stress-sensitive corticolimbic circuits in adversity-related psychopathology. Structure–function coupling (SFC) is a multimodal marker that is sensitive to developmental plasticity. While emerging evidence suggests cortical SFC is sensitive to adversity exposure during early childhood, it is unknown how SFC in stress-sensitive corticolimbic circuits links adversity exposure with mental health across development. We examined associations between adversity exposure, transdiagnostic symptomatology, and both amygdala–cortical and hippocampal–cortical SFC across development in a large youth sample (N = 607, 39% F). Results revealed that adversity exposure moderated the association between age and amygdala–ventromedial prefrontal cortex (vmPFC) SFC (partial R2 = 0.015; p = 0.007), such that age was positively associated with amygdala–vmPFC SFC in youth with higher, but not lower, levels of adversity exposure. Furthermore, amygdala–vmPFC SFC moderated the association between adversity exposure and internalizing symptoms (partial R2 = 0.015; p = 0.012), such that the adversity–symptoms association was reduced in youth with stronger, but not weaker, amygdala–vmPFC SFC. Separately, higher adversity exposure was associated with weaker hippocampal–limbic SFC (partial R2 = 0.019; p = 0.037), which moderated the association between adversity and internalizing symptoms (partial R2 = 0.005; p = 0.010) such that the adversity–symptoms association was reduced in youth with weaker, but not stronger, hippocampal–limbic SFC. These findings highlight that neurodevelopment of amygdala–vmPFC and hippocampal–limbic circuits may adapt in distinct ways to support mental health following adversity, with implications for risk and resilience against internalizing psychopathology.