Early life stress alters lifespan trajectories of amygdala development: a cross-species model of amygdala burnout
- 1University of Manchester
Abstract
Early-life stress is associated with alterations in amygdala volume, but findings vary across studies and species. Rodent models typically report increased amygdala volume, whereas human studies often find reductions or mixed effects. We propose the amygdala burnout hypothesis, which suggests that early-life stress alters amygdala developmental trajectories, producing initial volumetric increases that are followed by reductions later in life. To test this hypothesis, we examined amygdala development across rodent and human cohorts spanning adolescence to older adulthood. In rodents, chronic stress was associated with increased amygdala nuclei volumes during adolescence. Comparable increases were observed in adolescents from the IMAGEN consortium, with evidence of a dose-dependent association between childhood stress and amygdala developmental trajectories. In contrast, analyses of older adults from the UK Biobank revealed reduced bilateral amygdala volume associated with early-life stress. Together, these findings support a developmental model that reconciles previously conflicting observations across species and age groups. Early-life stress is associated with alterations in amygdala volume, but findings vary across studies and species. Rodent models typically report increased amygdala volume, whereas human studies often find reductions or mixed effects. We propose the amygdala burnout hypothesis, which suggests that early-life stress alters amygdala developmental trajectories, producing initial volumetric increases that are followed by reductions later in life. To test this hypothesis, we examined amygdala development across rodent and human cohorts spanning adolescence to older adulthood. In rodents, chronic stress was associated with increased amygdala nuclei volumes during adolescence. Comparable increases were observed in adolescents from the IMAGEN consortium, with evidence of a dose-dependent association between childhood stress and amygdala developmental trajectories. In contrast, analyses of older adults from the UK Biobank revealed reduced bilateral amygdala volume associated with early-life stress. Together, these findings support a developmental model that reconciles previously conflicting observations across species and age groups.
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BibTeX
@misc{sheppard2026early,
title = {{Early life stress alters lifespan trajectories of amygdala development: a cross-species model of amygdala burnout}},
author = {M. Sheppard and J. R. Toledo and L. A. Trujillo Villarreal and M. C. Litwinczuk and K. L. Moran and E. McManus and R. Elliott and N. W. Duncan and E. A. Garza-Villarreal and T. Banaschewski and G. Barker and A. L. Bokde and R. Bruhl and S. Desrivieres and H. Flor and A. Grigis and A. Heinz and F. Nees and D. Papadopoulos Orfanos and L. Poustka and M. N. Smolka and N. E. Holz and N. Vaidya and H. Walter and R. Whelan and P. Wirsching and G. Schumann and IMAGEN Consortium and N. Muhlert},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.04.749366},
url = {https://www.biorxiv.org/content/10.64898/2026.09.04.749366v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Early life stress alters lifespan trajectories of amygdala development: a cross-species model of amygdala burnout
AU - M. Sheppard
AU - J. R. Toledo
AU - L. A. Trujillo Villarreal
AU - M. C. Litwinczuk
AU - K. L. Moran
AU - E. McManus
AU - R. Elliott
AU - N. W. Duncan
AU - E. A. Garza-Villarreal
AU - T. Banaschewski
AU - G. Barker
AU - A. L. Bokde
AU - R. Bruhl
AU - S. Desrivieres
AU - H. Flor
AU - A. Grigis
AU - A. Heinz
AU - F. Nees
AU - D. Papadopoulos Orfanos
AU - L. Poustka
AU - M. N. Smolka
AU - N. E. Holz
AU - N. Vaidya
AU - H. Walter
AU - R. Whelan
AU - P. Wirsching
AU - G. Schumann
AU - IMAGEN Consortium
AU - N. Muhlert
PY - 2026
DA - 2026/09/04
PB - bioRxiv
DO - 10.64898/2026.09.04.749366
UR - https://www.biorxiv.org/content/10.64898/2026.09.04.749366v1
AB - Early-life stress is associated with alterations in amygdala volume, but findings vary across studies and species. Rodent models typically report increased amygdala volume, whereas human studies often find reductions or mixed effects. We propose the amygdala burnout hypothesis, which suggests that early-life stress alters amygdala developmental trajectories, producing initial volumetric increases that are followed by reductions later in life. To test this hypothesis, we examined amygdala development across rodent and human cohorts spanning adolescence to older adulthood. In rodents, chronic stress was associated with increased amygdala nuclei volumes during adolescence. Comparable increases were observed in adolescents from the IMAGEN consortium, with evidence of a dose-dependent association between childhood stress and amygdala developmental trajectories. In contrast, analyses of older adults from the UK Biobank revealed reduced bilateral amygdala volume associated with early-life stress. Together, these findings support a developmental model that reconciles previously conflicting observations across species and age groups. Early-life stress is associated with alterations in amygdala volume, but findings vary across studies and species. Rodent models typically report increased amygdala volume, whereas human studies often find reductions or mixed effects. We propose the amygdala burnout hypothesis, which suggests that early-life stress alters amygdala developmental trajectories, producing initial volumetric increases that are followed by reductions later in life. To test this hypothesis, we examined amygdala development across rodent and human cohorts spanning adolescence to older adulthood. In rodents, chronic stress was associated with increased amygdala nuclei volumes during adolescence. Comparable increases were observed in adolescents from the IMAGEN consortium, with evidence of a dose-dependent association between childhood stress and amygdala developmental trajectories. In contrast, analyses of older adults from the UK Biobank revealed reduced bilateral amygdala volume associated with early-life stress. Together, these findings support a developmental model that reconciles previously conflicting observations across species and age groups.
ER -