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Long-term Neural Embedding of Childhood Adversity in a Population-Representative Birth Cohort Followed for 5 Decades

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Maria Z. Gehred, Annchen R. Knodt, Antony Ambler, Kyle J. Bourassa, Andrea Danese, Maxwell L. Elliott, Sean Hogan, David Ireland, Richie Poulton, Sandhya Ramrakha, Aaron Reuben, Maria L. Sison, Terrie E. Moffitt, Ahmad R. Hariri, Avshalom Caspi

Original languageEnglish
Pages (from-to)182-193
Number of pages12
JournalBiological psychiatry
Volume90
Issue number3
DOIs
Accepted/In press2021
Published1 Aug 2021

Bibliographical note

Funding Information: This work was supported by the National Institute on Aging (Grant Nos. R01AG032282 [to TEM] and R01AG049789 [to TEM and ARH] and Training Grant No. T32-AG000029 [to KJB]), Medical Research Council (Grant No. MR/P005918/1 [to TEM and AC] ), Jacobs Foundation , National Institute of Environmental Health Sciences (Grant No. F31ES029358 [to AR], and National Science Foundation Graduate Research Fellowship (Grant No. NSF DGE-1644868 [to MLE]). The Dunedin Multidisciplinary Health and Development Research Unit was supported by the New Zealand Health Research Council and New Zealand Ministry of Business, Innovation, and Employment. Funding Information: This work was supported by the National Institute on Aging (Grant Nos. R01AG032282 [to TEM] and R01AG049789 [to TEM and ARH] and Training Grant No. T32-AG000029 [to KJB]), Medical Research Council (Grant No. MR/P005918/1 [to TEM and AC]), Jacobs Foundation, National Institute of Environmental Health Sciences (Grant No. F31ES029358 [to AR], and National Science Foundation Graduate Research Fellowship (Grant No. NSF DGE-1644868 [to MLE]). The Dunedin Multidisciplinary Health and Development Research Unit was supported by the New Zealand Health Research Council and New Zealand Ministry of Business, Innovation, and Employment. MZG, TEM, ARH, and AC conceptualized and designed the current study. All authors were involved in data acquisition, analysis, or interpretation. MZG, TEM, ARH, and AC drafted the manuscript, and all authors provided critical revisions of the manuscript for important intellectual content. MZG, ARK, MLE, and MLS conducted the statistical analyses. RP, TEM, ARH, and AC obtained funding for the study. Administrative and technical support were provided by AA, SH, DI, RP, and SR. The project was supervised by TEM, ARH, and AC. We thank members of the Advisory Board for the Dunedin Neuroimaging Study, Dunedin Study members, unit research staff, Pacific Radiology Group staff, and Dunedin Study founder Phil Silva, Ph.D. University of Otago. The authors report no biomedical financial interests or potential conflicts of interest. Publisher Copyright: © 2021 Society of Biological Psychiatry Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

King's Authors

Abstract

Background: Childhood adversity has been previously associated with alterations in brain structure, but heterogeneous designs, methods, and measures have contributed to mixed results and have impeded progress in mapping the biological embedding of childhood adversity. We sought to identify long-term differences in structural brain integrity associated with childhood adversity. Methods: Multiple regression was used to test associations between prospectively ascertained adversity during childhood and adversity retrospectively reported in adulthood with structural magnetic resonance imaging measures of midlife global and regional cortical thickness, cortical surface area, and subcortical gray matter volume in 861 (425 female) members of the Dunedin Study, a longitudinal investigation of a population-representative birth cohort. Results: Both prospectively ascertained childhood adversity and retrospectively reported adversity were associated with alterations in midlife structural brain integrity, but associations with prospectively ascertained childhood adversity were consistently stronger and more widely distributed than associations with retrospectively reported childhood adversity. Sensitivity analyses revealed that these associations were not driven by any particular adversity or category of adversity (i.e., threat or deprivation) or by childhood socioeconomic disadvantage. Network enrichment analyses revealed that these associations were not localized but were broadly distributed along a hierarchical cortical gradient of information processing. Conclusions: Exposure to childhood adversity broadly is associated with widespread differences in midlife gray matter across cortical and subcortical structures, suggesting that biological embedding of childhood adversity in the brain is long lasting, but not localized. Research using retrospectively reported adversity likely underestimates the magnitude of these associations. These findings may inform future research investigating mechanisms through which adversity becomes embedded in the brain and influences mental health and cognition.

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