Distinct spatial associations of adversity with hippocampal macro- and microstructure in early adolescence

Marsiglia, M.; Eriguec, D. Y.; Serio, B.; Hettwer, M. D.; DeKraker, J.; Waite, L.; Hoffstaedter, F.; Bernhardt, B.; Eickhoff, S. B.; Valk, S. L.

doi:10.64898/2026.07.30.741706

bioRxiv · 10.64898/2026.07.30.741706

Distinct spatial associations of adversity with hippocampal macro- and microstructure in early adolescence

Marsiglia, M.·Eriguec, D. Y.·Serio, B.·Hettwer, M. D.·DeKraker, J.·Waite, L.·Hoffstaedter, F.·Bernhardt, B.·Eickhoff, S. B.·Valk, S. L.

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Abstract

Youth adversity has been associated with alterations in hippocampal structure; however, it remains unclear whether different forms of adversity relate distinctly to its organization across the anterior-posterior and proximal-distal axes. Here, we investigated the associations of different types of adversity with multiple structural properties of the hippocampus in 5,263 early adolescents from the ABCD Study. Hippocampal macrostructure was characterized using volume, thickness, and gyrification, whereas T1w/T2w ratio served as an in vivo proxy for microstructure. Adversity was assessed at the family level using questionnaires on family environment and parenting, and at the socioeconomic level using income-to-needs ratio and neighborhood disadvantage measured by the Area Deprivation Index. Associations were examined for each adversity type separately in multi-variate analyses and for cumulative adversity exposure in univariate models. Hippocampal features were obtained using HippUnfold, an advanced automatic segmentation approach that accounts for interindividual folding variability, and were analyzed globally as well as across the hippocampal anterior-posterior and proximal-distal axes. Socioeconomic measures showed widespread associations with hippocampal macrostructure across the whole hippocampus and both anatomical axes, whereas associations with T1w/T2w ratio were limited and observed only for neighborhood disadvantage along the anterior-posterior axis. Cumulative adversity exposure was consistently associated with alterations in CA1 and subiculum across volume, thickness, and gyrification, but not T1w/T2w ratio. Together, these findings suggest that different types of adversity exhibit distinct spatial associations across complementary hippocampal macro- and microstructural features, highlighting regional variation in the susceptibility of the developing hippocampus to environmental adversity.

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Marsiglia, M., Eriguec, D. Y., Serio, B., Hettwer, M. D., DeKraker, J., Waite, L., Hoffstaedter, F., Bernhardt, B., Eickhoff, S. B., Valk, S. L.. 2026-07-31. Distinct spatial associations of adversity with hippocampal macro- and microstructure in early adolescence. https://doi.org/10.64898/2026.07.30.741706

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