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bioRxiv · 10.64898/2025.12.22.696017

Corticolimbic structure-function coupling is sensitive to childhood adversity and buffers adversity-related symptoms during development

Sisk, L. M.·Keding, T. J.·Drew, A.·Ma, E.·Shafiei, G.·Cieslak, M.·Satterthwaite, T. D.·Gee, D. G.
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Abstract

Childhood adversity is a potent predictor of mental health problems across the lifespan, and a rich cross-species literature implicates stress-sensitive corticolimbic circuits in adversity-related psychopathology. Structure-function coupling (SFC) is a promising 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 sample of youth (N = 607, 39% F). Results revealed that adversity exposure moderated age-related change in amygdala-vmPFC SFC (p = .007), such that youth exposed to higher, but not lower, levels of adversity showed an age-related increase in amygdala-vmPFC SFC. Further, amygdala-vmPFC SFC buffered the effect of adversity on internalizing symptoms (p = .012), such that those youth with higher adversity exposure who had stronger amygdala-vmPFC SFC also displayed lower internalizing symptoms. Separately, higher adversity exposure was associated with lower hippocampal-limbic network SFC (p = .037), which moderated the effect of adversity on internalizing symptoms (p = .010). These findings highlight that structural and functional neurodevelopment of amygdala-vmPFC and hippocampal-limbic network connections may adapt in distinct ways to support mental health following adversity, with implications for risk and resilience against internalizing psychopathology. Significance StatementDelineating how childhood adversity alters neurodevelopment is critical to understanding the origins of adversity-related risk for mental health disorders. Here, we leverage a multimodal marker of the correspondence between brain structure and function to test how corticolimbic circuits are jointly shaped by adversity exposure. Results reveal that the structure-function coupling of amygdala-vmPFC and hippocampal-limbic networks is associated with adversity exposure and differentially moderate risk for internalizing psychopathology. These findings suggest key roles for neural stress regulation and memory circuits in adapting to support optimal functioning following adversity exposure, and highlight the concordance of neural structure and function as an important indicator of individual-level risk and resilience.

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Sisk, L. M., Keding, T. J., Drew, A., Ma, E., Shafiei, G., Cieslak, M., Satterthwaite, T. D., Gee, D. G.. 2025-12-24. Corticolimbic structure-function coupling is sensitive to childhood adversity and buffers adversity-related symptoms during development. https://doi.org/10.64898/2025.12.22.696017

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