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

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 R 2 = 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 R 2 = 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 R 2 = 0.019; p = 0.037), which moderated the association between adversity and internalizing symptoms (partial R 2 = 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.