# The moderating effect of lifetime physical activity on brain alterations related to adverse childhood experiences

**Authors:** Lemye Zehirlioglu, Traute Demirakca, Richard Nkrumah, Lennart Ettingshausen, Yasmin Grauduszus, Claudius von Schröder, Melissa Feichtmair, Nikolaus Kleindienst, Gabriele Ende, Christian Schmahl

PMC · DOI: 10.1192/j.eurpsy.2025.10116 · 2025-10-20

## TL;DR

This study shows that physical activity can reduce the impact of childhood trauma on the amygdala, a brain region linked to stress and emotion.

## Contribution

The study reveals that lifetime physical activity moderates the relationship between childhood adversity and amygdala volume.

## Key findings

- Lifetime physical activity significantly moderates the effect of ACEs on amygdala volume.
- Only individuals with low physical activity showed increased amygdala volume due to ACEs.
- The interaction explained 7.9% of the variance in amygdala volume.

## Abstract

Adverse childhood experiences (ACEs) can cause morphological brain alterations across the lifespan, contributing to increased vulnerability to mental and physical disorders. Despite extensive research on ACEs-related brain alterations, the protective or augmenting role of modifiable lifestyle factors such as physical activity has been largely underexplored, representing a key gap in our understanding of trauma-related neuroplasticity. To close this gap, we aimed to investigate how lifetime physical activity (LPA) influences the relationship between ACEs and morphological brain alterations.

Moderation analyses using Hayes’ PROCESS macro examined the interaction between ACEs and LPA on the volume of limbic system-related regions – hippocampus, amygdala, anterior cingulate cortex (n = 81).

While LPA showed no moderating effect on hippocampal or anterior cingulate volume, the model concerning the volume of the amygdala was significant. This model explained 8.1% of the variance in amygdala volume (p = 0.002) and the interaction of LPA and ACEs contributed 7.9% of this variance, with a significant effect (β = −0.221 p ≤ 0.001). That indicated LPA moderates ACEs-related structural changes in the amygdala, a key component of the central circuitry of emotion and stress sensitization. Notably, only in individuals with low physical activity were ACEs associated with increased volume of amygdala.

Our findings underscore the behavioral dependency of the structural adaptations of the amygdala following childhood adversities. These results emphasize the therapeutic potential of incorporating physical activity into interventions for trauma-exposed individuals, offering a behavioral approach to mitigating stress-related neurobiological changes.

## Full-text entities

- **Genes:** BDNF (brain derived neurotrophic factor) [NCBI Gene 627] {aka ANON2, BULN2}, IGF1 (insulin like growth factor 1) [NCBI Gene 3479] {aka IGF, IGF-I, IGFI, MGF}, AP2B1 (adaptor related protein complex 2 subunit beta 1) [NCBI Gene 163] {aka ADTB2, AP105B, AP2-BETA, CLAPB1}, LPA (lipoprotein(a)) [NCBI Gene 4018] {aka AK38, APOA, LP}
- **Diseases:** brain alterations (MESH:D001927), anxiety (MESH:D001007), mood disorders (MESH:D019964), cardio-metabolic diseases (MESH:D008659), BPD (MESH:D001883), depression (MESH:D003866), Trauma (MESH:D014947), alterations (MESH:D004408), PA (MESH:D059445), ACEs (MESH:D003643), bipolar disorder (MESH:D001714), abuse (MESH:D019966), neglect (MESH:D058069), schizophrenia (MESH:D012559), obesity (MESH:D009765), HPA dysregulation (MESH:D007029), TD (MESH:D004409), PTSD (MESH:D013313), mental and physical disorders (MESH:D001523), emotional, physical, and sexual abuse (MESH:D000082002)
- **Chemicals:** lactate (MESH:D019344)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12646122/full.md

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Source: https://tomesphere.com/paper/PMC12646122