# Echoes of childhood trauma: the relationship between adverse childhood experiences, brain structure, and mental health in aging adults

**Authors:** Anne Klimesch, Leonie Ascone, Götz Thomalla, Bastian Cheng, Marvin Petersen, Ingo Schäfer, Jürgen Gallinat, Simone Kühn

PMC · DOI: 10.1038/s41398-026-03811-2 · 2026-02-03

## TL;DR

Childhood trauma is linked to mental health issues and brain changes in older adults, with more severe trauma causing wider brain effects.

## Contribution

This study provides evidence of long-term brain structural changes linked to childhood trauma in aging adults.

## Key findings

- ACEs are associated with mental health symptoms in mid- to late adulthood.
- Individuals with 3 or more ACEs show significant grey matter volume reductions in limbic and frontal regions.
- More severe ACE exposure (4 or more) leads to widespread neuroanatomical alterations.

## Abstract

Adverse childhood experiences (ACEs) are associated with persistent mental health risks and brain structural differences across adulthood, yet their long-term neurobiological relevance in aging populations remains unclear. Given that ACEs are common and societies are aging, understanding how early adversity relates to mental and brain health across the lifespan is an important goal. This preregistered study examined whether ACEs are associated with mental health symptoms in mid- to late adulthood, and whether regional brain structure may account for part of this relationship. Cross-sectional data of the Hamburg City Health Study were used, involving participants aged 46–78 years with available magnetic resonance imaging data (Ntotal = 2 624; eligible: nanalysis sample = 1 900). Mental health status was quantified using the Patient Health Questionnaire-9 and the General Anxiety Disorder-7 questionnaire, while ACEs were assessed using the 10-item ACE-questionnaire. Predefined regions of interest (ROI) were the hippocampus, amygdala, and dorsolateral prefrontal cortex. Bayesian statistical analysis provided strong evidence for an association between ACEs and both mental health outcomes but did not confirm the hypothesized mediation by ROI-level brain morphology. Exploratory whole-brain voxel-based morphometry revealed significant regional grey matter volume (rGMV) reductions in individuals with 3 or more ACEs, affecting bilateral limbic and frontal regions—including the nucleus accumbens, gyrus rectus, and insula. These reductions were more pronounced and widespread in individuals with 4 or more ACEs, extending to areas in the dorsolateral and medial prefrontal cortex, anterior cingulate cortex, inferior parietal and temporal gyri, occipital cortex, and cerebellum. Notably, no increases in rGMV were observed for any ACE group. This suggests a dose-dependent effect, with 4 or more ACEs marking a potential threshold for more distributed neuroanatomical alterations. These results derived from a representative general population study extend the understanding of the possible effects of ACEs by providing evidence that structural changes associated with ACEs could last into mid and late adulthood similarly to mental health outcomes.

## Full-text entities

- **Genes:** GAD1 (glutamate decarboxylase 1) [NCBI Gene 2571] {aka CPSQ1, DEE89, GAD, GAD-67, SCP}, ACE (angiotensin I converting enzyme) [NCBI Gene 1636] {aka ACE1, CD143, DCP, DCP1}, ACE3P (angiotensin I converting enzyme 3, pseudogene) [NCBI Gene 100129123] {aka ACE3}, AP2B1 (adaptor related protein complex 2 subunit beta 1) [NCBI Gene 163] {aka ADTB2, AP105B, AP2-BETA, CLAPB1}, ACE2 (angiotensin converting enzyme 2) [NCBI Gene 59272] {aka ACEH}
- **Diseases:** somatic and mental disorders (MESH:D013001), mood disorders (MESH:D019964), Generalized Anxiety Disorder (MESH:C000726808), GAD-7 (MESH:C537955), anxiety (MESH:D001007), depression (MESH:D003866), Covid-19 (MESH:D000086382), Anxiety Disorder (MESH:D001008), Trauma (MESH:D014947), physical abuse (MESH:D059445), ACEs (MESH:D003643), major depression (MESH:D003865), abuse (MESH:D019966), emotional neglect (MESH:D058069), adverse (MESH:D064420), neurodegeneration (MESH:D019636), mental disorder (MESH:D001523), sexual abuse (MESH:D000082002), mental health disorder (OMIM:603663), child abuse (MESH:C535569)
- **Chemicals:** GMV (-)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Mutations:** S089662730200569X

## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12873319/full.md

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Source: https://tomesphere.com/paper/PMC12873319