Evidence map›Paper›PMID 41378202›Full record

ArticleNeurobiology of stress2025

Sensitive periods for the link between childhood maltreatment and brain aging during adulthood.

Leland L Fleming, Kyoko Ohashi, Michelle Bosquet Enlow, Jennifer Khoury, Torsten Klengel, Karlen Lyons-Ruth, Martin Teicher, Kerry J Ressler

Abstract read
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Article in Neurobiology of stress, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Leland L FlemingDivision of Depression and Anxiety, McLean Hospital, Belmont, USA.
Kyoko OhashiDepartment of Psychiatry, Harvard Medical School, Boston, USA.
Michelle Bosquet EnlowDepartment of Psychiatry, Harvard Medical School, Boston, USA.
Jennifer KhouryDepartment of Psychology, Mount Saint Vincent University, Canada.
Torsten KlengelDepartment of Psychiatry, Harvard Medical School, Boston, USA.
Karlen Lyons-RuthDepartment of Psychiatry, Harvard Medical School, Boston, USA.
Martin TeicherDepartment of Psychiatry, Harvard Medical School, Boston, USA.
Kerry J ResslerDivision of Depression and Anxiety, McLean Hospital, Belmont, USA.

Funding

Cell Type Specific Genomic and Functional Dissection of Fear-Off Amygdala PathwaysR01MH108665 · NIMH · MCLEAN HOSPITAL · PI BOLSHAKOV, VADIM, RESSLER, KERRY J. · 2016 to 2025
$7.5M
Neurobiology of Mothering and Infant StressR01HD079484 · NICHD · MCLEAN HOSPITAL · PI BOSQUET ENLOW, MICHELLE A, GRANT, PATRICIA ELLEN · 2015 to 2019
$3.6M
Transgenerational Impact of Childhood Maltreatment on Structural/Functional Properties of Visual CortexK00HD111352 · NICHD · MCLEAN HOSPITAL · PI FLEMING, LELAND · 2022 to 2025
$359k
NICHD NIH HHS K00 HD111352NICHD NIH HHS R01 HD079484NIMH NIH HHS R01 MH108665
6 · The paper itself

Abstract

Background: Childhood maltreatment (CM) is associated with the early onset of psychopathology and accelerated biological aging. However, outcomes vary widely among individuals with CM history. This variability may, in part, be explained by differences in age of exposure to CM. In this study, we examined whether CM was associated with accelerated brain aging, depending on the timing of exposure (i.e., 'sensitive periods'). Method: A machine learning algorithm of brain age trained prior to the current study in 3377 healthy individuals was employed in a CM dataset of 150 adult postnatal women, 92 of whom provided MRI data. CM history was retrospectively assessed from birth to age 18 years. Brain-predicted age was calculated from T1-weighted MRI scans. Brain age gap (BAG) was quantified as the disparity between brain-predicted age, relative to chronological age. Sensitive periods were identified using random forest regression with conditional inference trees. Results: CM severity was associated with greater BAG (β = 0.34, p < 0.001). The most robust type/time risk factors for greater BAG were parental verbal abuse between ages 7 and 15 years, parental physical abuse between ages 4 and 6 years, witnessing sibling violence between ages 4 and 15 years, and sexual abuse between ages 4-6. Parental verbal abuse (7-15 years) and parental physical abuse (4-6) were the variables that were the most important predictors above and beyond duration, multiplicity (number of exposures), and cumulative maltreatment severity. Conclusion: These findings suggest a link between CM and accelerated brain aging, with certain developmental periods appearing more sensitive to these effects. To the best of our knowledge, this study is the first to identify sensitive periods for the link between CM and brain aging in adults, and the first to examine the link between CM and brain aging in postnatal women. Together, these results suggest that CM's association with brain development is complex and warrants nuanced approaches to investigating the possible mechanisms underlying its effects.

Identifiers

PMID41378202
PMCPMC12686658

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.