Sex-specific associations of childhood adversity with frontostriatal network organization and anhedonia in young adulthood

Shepherd, R. J.; Pierce, M.; Muhlert, N.; Komarnyckyj, M.; Sheppard, M.; Banaschewski, T.; Barker, G.; Bokde, A.; Brühl, R.; Desrivieres, S.; Flor, H.; Gowland, P.; Grigis, A.; Heinz, A.; Nees, F.; Papadopoulos Orfanos, D.; Poustka, L.; Smolka, M. N.; Holz, N.; Vaidya, N.; Walter, H.; Whelan, R.; Wirsching, P.; Schumann, G.; IMAGEN Consortium,; Elliott, R.

doi:10.64898/2026.07.24.740545

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bioRxiv · 10.64898/2026.07.24.740545

Sex-specific associations of childhood adversity with frontostriatal network organization and anhedonia in young adulthood

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Abstract

IntroductionAnhedonia is a transdiagnostic psychiatric symptom linked to increased functional connectivity between the prefrontal cortex and striatum. Here, we examined how dimensions of early adversity contribute to this profile of connectivity. MethodsIn a European community sample of young adults (IMAGEN), we examined cross-sectional (n=613) and longitudinal (n=332) associations of adversity dimensions with resting-state fMRI-derived connectivity. We selected 10 ROIs from anhedonia literature, defined in the functional images as 4mm-radius spheres. We then used network-based regression models to identify clusters of ROI-ROI connections associated with threat and deprivation scores, using interaction terms to examine sex and age-specific associations. We also examined associations between adversity and anhedonia, operationalized using factor analysis of six items from self-report surveys. ResultsAt age 18-22, we identified sex-specific associations between deprivation and connectivity for a cluster of 9 ROI-ROI connections (p-FWE=0.038), primarily involving the nucleus accumbens. Specifically, we observed positive associations between deprivation and connectivity in males, and negative associations in females. In the longitudinal analysis, negative deprivation associations in females attenuated with age for a cluster of 14 connections (p-FWE=0.009). A cluster of 17 connections also had initial positive associations with threat in females that attenuated with age (p-FWE=0.008). No such longitudinal changes were observed in males. Higher deprivation was linked to increased later anhedonia in males but not females (p=0.026). ConclusionCompared to females, young adult males may be more vulnerable to developing anhedonia after experiencing deprivation in childhood. Dimensions of early adversity are linked to distinct pathways of frontostriatal development.

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Shepherd, R. J., Pierce, M., Muhlert, N., Komarnyckyj, M., Sheppard, M., Banaschewski, T., Barker, G., Bokde, A., Brühl, R., Desrivieres, S., Flor, H., Gowland, P., Grigis, A., Heinz, A., Nees, F., Papadopoulos Orfanos, D., Poustka, L., Smolka, M. N., Holz, N., Vaidya, N., Walter, H., Whelan, R., Wirsching, P., Schumann, G., IMAGEN Consortium,, Elliott, R.. 2026-07-28. Sex-specific associations of childhood adversity with frontostriatal network organization and anhedonia in young adulthood. https://doi.org/10.64898/2026.07.24.740545

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