No robust evidence for an interaction between early-life adversity and protective factors on global and regional brain volumes

Andrea P. Cortes Hidalgo; Henning Tiemeier; Stephen A. Metcalf; Maximilian Monninger; Andreas Meyer-Lindenberg; Pascal M. Aggensteiner; Marian J. Bakermans‑Kranenburg; Tonya White; Tobias Banaschewski; Marinus H. van IJzendoorn; Nathalie E. Holz

doi:10.1016/j.dcn.2022.101166

No robust evidence for an interaction between early-life adversity and protective factors on global and regional brain volumes

Andrea P. Cortes Hidalgo^*
, Henning Tiemeier
, Stephen A. Metcalf
, Maximilian Monninger
, Andreas Meyer-Lindenberg
, Pascal M. Aggensteiner
, Marian J. Bakermans‑Kranenburg
, Tonya White
, Tobias Banaschewski
, Marinus H. van IJzendoorn
, Nathalie E. Holz

^*Corresponding author for this work

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

Childhood adversity is associated with brain morphology and poor psychological outcomes, and evidence of protective factors counteracting childhood adversity effects on neurobiology is scarce. We examined the interplay of childhood adversity with protective factors in relation to brain morphology in two independent longitudinal cohorts, the Generation R Study (N = 3008) and the Mannheim Study of Children at Risk (MARS) (N = 179). Cumulative exposure to 12 adverse events was assessed across childhood until age 9 years in Generation R and 11 years in MARS. Protective factors (temperament, cognition, self-esteem, maternal sensitivity, friendship quality) were assessed at various time-points during childhood. Global brain volumes and volumes of amygdala, hippocampus, and the anterior cingulate, medial orbitofrontal and rostral middle frontal cortices were assessed with anatomical scans at 10 years in Generation R and at 25 years in MARS. Childhood adversity was related to smaller cortical grey matter, cerebral white matter, and cerebellar volumes in children. Also, no buffering effects of protective factors on the association between adversity and the brain outcomes survived multiple testing correction. We found no robust evidence for an interaction between protective factors and childhood adversity on broad brain structural measures. Small interaction effects observed in one cohort only warrant further investigation.

Original language	English
Article number	101166
Pages (from-to)	1-13
Number of pages	13
Journal	Developmental Cognitive Neuroscience
Volume	58
Early online date	25 Oct 2022
DOIs	https://doi.org/10.1016/j.dcn.2022.101166
Publication status	Published - Dec 2022

Bibliographical note

Publisher Copyright:
© 2022 The Authors

Funding

The authors gratefully acknowledge financial support by a short-term research grant from the German Academic Exchange Service (DAAD) to APCH, a ZonMw VICI grant awarded to HT (project number 016.VICI.170.200), and an award from the Netherlands Organization for Scientific Research (NWO; Spinoza prize) to MHVIJ. MJB-K was supported by the European Research Council (ERC AdG 669249). MHVIJ and MJB-K were also supported by the Gravitation program of the Dutch Ministry of Education, Culture, and Science and the NWO (024.001.003). SAM was supported by an Open Research Award from the Fulbright US Student Program and a Gates Cambridge Scholarship from the Gates Cambridge Trust (Bill & Melinda Gates Foundation grant OPP1144). AML acknowledges grant support by the German Research Foundation (DFG, Research Training Group GRK2350/1 project B02, Collaborative Research Center SFB 1158 project B09, Collaborative Research Center TRR 265 project S02, Grant ME 1591/4-1), German Federal Ministry of Education and Research (BMBF, Grants 01EF1803A, 01ZX1314G, 01GQ1003B), European Union's Seventh Framework Programme (FP7, Grants 602450, 602805, 115300, HEALTH-F2-2010-241909), Innovative Medicines Initiative Joint Undertaking (IMI, Grant 115008) and Ministry of Science, Research and the Arts of the State of Baden-Wuerttemberg, Germany (MWK, Grant 42-04HV.MED (16)/16/1).NEH gratefully acknowledges grants from the German Research Foundation (Grant nos. DFG HO 5674/2-1, GRK2350/1), the Radboud University (Radboud Excellence Fellowship) and the Ministry of Science, Research and the Arts of the State of Baden-W\u00FCrttemberg, Germany (Special support program SARS CoV-2 pandemic).The general design of the Generation R Study received financial support from the Erasmus Medical Center, Rotterdam, the Erasmus University Rotterdam, ZonMw, the Netherlands Organisation for Scientific Research (NWO), and the Dutch Ministry of Health, Welfare and Sport. Neuroimaging and the neuroimaging infrastructure were supported by ZonMw TOP grant awarded to TW (Project no. 91211021). Supercomputing resources were provided by NWO (www.surfsara.nl, Cartesius).This work was supported, in whole or in part, by the Bill & Melinda Gates Foundation [Grant OPP1144]. Under the grant conditions of the Foundation, a Creative Commons Attribution 4.0 Generic License has already been assigned to the Author Accepted Manuscript version that might arise from this submission. NEH gratefully acknowledges grants from the German Research Foundation (Grant nos. DFG HO 5674/2-1 , GRK2350/1 ), the Radboud University (Radboud Excellence Fellowship) and the Ministry of Science , Research and the Arts of the State of Baden-W\u00FCrttemberg, Germany (Special support program SARS CoV-2 pandemic). The authors gratefully acknowledge financial support by a short-term research grant from the German Academic Exchange Service (DAAD) to APCH, a ZonMw VICI grant awarded to HT (project number 016.VICI.170.200), and an award from the Netherlands Organization for Scientific Research (NWO; Spinoza prize) to MHVIJ. MJB-K was supported by the European Research Council (ERC AdG 669249 ). MHVIJ and MJB-K were also supported by the Gravitation program of the Dutch Ministry of Education , Culture, and Science and the NWO ( 024.001.003 ). SAM was supported by an Open Research Award from the Fulbright US Student Program and a Gates Cambridge Scholarship from the Gates Cambridge Trust ( Bill & Melinda Gates Foundation grant OPP1144 ). AML acknowledges grant support by the German Research Foundation (DFG, Research Training Group GRK2350/1 project B02, Collaborative Research Center SFB 1158 project B09, Collaborative Research Center TRR 265 project S02, Grant ME 1591/4-1 ), German Federal Ministry of Education and Research (BMBF, Grants 01EF1803A , 01ZX1314G , 01GQ1003B ), European Union\u2019s Seventh Framework Programme (FP7, Grants 602450 , 602805 , 115300 , HEALTH-F2-2010-241909 ), Innovative Medicines Initiative Joint Undertaking (IMI, Grant 115008 ) and Ministry of Science, Research and the Arts of the State of Baden-Wuerttemberg , Germany (MWK, Grant 42-04HV.MED (16)/16/1 ). TW has received grant or research support from the Sophia Children\u2019s Hospital Foundation, the Simons Foundation Autism Research Initiative, and the Netherlands Organisation for Health Research and Development (ZonMw). She is Editor-in-Chief for Aperture: The Journal of the Organization for Human Brain Mapping, and has served on the editorial board of Neuroinformatics and is guest editing an edition on Neuroimaging in the Global Context in NeuroImage. The general design of the Generation R Study received financial support from the Erasmus Medical Center, Rotterdam, the Erasmus University Rotterdam, ZonMw, the Netherlands Organisation for Scientific Research (NWO), and the Dutch Ministry of Health , Welfare and Sport. Neuroimaging and the neuroimaging infrastructure were supported by ZonMw TOP grant awarded to TW (Project no. 91211021). Supercomputing resources were provided by NWO ( www.surfsara.nl , Cartesius). This work was supported, in whole or in part, by the Bill & Melinda Gates Foundation [Grant OPP1144 ]. Under the grant conditions of the Foundation, a Creative Commons Attribution 4.0 Generic License has already been assigned to the Author Accepted Manuscript version that might arise from this submission.

Funders	Funder number
Gates Cambridge Scholarship from the Gates Cambridge Trust
Erasmus Universiteit Rotterdam
Ministry of Science, Research and the Arts of the state of Baden-Württemberg
Erasmus Medical Center, Rotterdam
Deutscher Akademischer Austauschdienst
ZonMw Vici
Ministry of Science , Research and the Arts of the State of Baden-Württemberg
Horizon 2020 Framework Programme
Dutch Ministry of Education , Culture, and Science
European Commission
Radboud Universitair Medisch Centrum
Ministerie van Volksgezondheid, Welzijn en Sport
Seventh Framework Programme	HEALTH-F2-2010-241909, 602805, 115300, 602450, 669249
ZonMw
Dutch Ministry of Education, Culture, and Science
Fulbright US Student Program
Simons Foundation Autism Research Initiative
European Research Council
Children’s Hospital Foundation
ZonMw TOP	91211021
Bundesministerium für Bildung und Forschung	01ZX1314G, 01EF1803A, 01GQ1003B
Bill and Melinda Gates Foundation	OPP1144
Deutsche Forschungsgemeinschaft	GRK2350/1, DFG HO 5674/2-1, ME 1591/4-1
Innovative Medicines Initiative	115008
???publication-publication-funding-organisation-not-added???	024.001.003
Ministerium für Wissenschaft, Forschung und Kunst Baden-Württemberg	MED (16)/16/1

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 1 No Poverty
SDG 3 Good Health and Well-being

Keywords

Adversity
Brain morphology
Child
Magnetic resonance imaging
Resilience

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10.1016/j.dcn.2022.101166

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Cite this

Cortes Hidalgo, A. P., Tiemeier, H., Metcalf, S. A., Monninger, M., Meyer-Lindenberg, A., Aggensteiner, P. M., Bakermans‑Kranenburg, M. J., White, T., Banaschewski, T., van IJzendoorn, M. H., & Holz, N. E. (2022). No robust evidence for an interaction between early-life adversity and protective factors on global and regional brain volumes. Developmental Cognitive Neuroscience, 58, 1-13. Article 101166. https://doi.org/10.1016/j.dcn.2022.101166

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title = "No robust evidence for an interaction between early-life adversity and protective factors on global and regional brain volumes",

abstract = "Childhood adversity is associated with brain morphology and poor psychological outcomes, and evidence of protective factors counteracting childhood adversity effects on neurobiology is scarce. We examined the interplay of childhood adversity with protective factors in relation to brain morphology in two independent longitudinal cohorts, the Generation R Study (N = 3008) and the Mannheim Study of Children at Risk (MARS) (N = 179). Cumulative exposure to 12 adverse events was assessed across childhood until age 9 years in Generation R and 11 years in MARS. Protective factors (temperament, cognition, self-esteem, maternal sensitivity, friendship quality) were assessed at various time-points during childhood. Global brain volumes and volumes of amygdala, hippocampus, and the anterior cingulate, medial orbitofrontal and rostral middle frontal cortices were assessed with anatomical scans at 10 years in Generation R and at 25 years in MARS. Childhood adversity was related to smaller cortical grey matter, cerebral white matter, and cerebellar volumes in children. Also, no buffering effects of protective factors on the association between adversity and the brain outcomes survived multiple testing correction. We found no robust evidence for an interaction between protective factors and childhood adversity on broad brain structural measures. Small interaction effects observed in one cohort only warrant further investigation.",

keywords = "Adversity, Brain morphology, Child, Magnetic resonance imaging, Resilience",

author = "\{Cortes Hidalgo\}, \{Andrea P.\} and Henning Tiemeier and Metcalf, \{Stephen A.\} and Maximilian Monninger and Andreas Meyer-Lindenberg and Aggensteiner, \{Pascal M.\} and Bakermans‑Kranenburg, \{Marian J.\} and Tonya White and Tobias Banaschewski and \{van IJzendoorn\}, \{Marinus H.\} and Holz, \{Nathalie E.\}",

note = "Publisher Copyright: {\textcopyright} 2022 The Authors",

year = "2022",

month = dec,

doi = "10.1016/j.dcn.2022.101166",

language = "English",

volume = "58",

pages = "1--13",

journal = "Developmental Cognitive Neuroscience",

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Cortes Hidalgo, AP, Tiemeier, H, Metcalf, SA, Monninger, M, Meyer-Lindenberg, A, Aggensteiner, PM, Bakermans‑Kranenburg, MJ, White, T, Banaschewski, T, van IJzendoorn, MH & Holz, NE 2022, 'No robust evidence for an interaction between early-life adversity and protective factors on global and regional brain volumes', Developmental Cognitive Neuroscience, vol. 58, 101166, pp. 1-13. https://doi.org/10.1016/j.dcn.2022.101166

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AU - Cortes Hidalgo, Andrea P.

AU - Tiemeier, Henning

AU - Metcalf, Stephen A.

AU - Monninger, Maximilian

AU - Meyer-Lindenberg, Andreas

AU - Aggensteiner, Pascal M.

AU - Bakermans‑Kranenburg, Marian J.

AU - White, Tonya

AU - Banaschewski, Tobias

AU - van IJzendoorn, Marinus H.

AU - Holz, Nathalie E.

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AB - Childhood adversity is associated with brain morphology and poor psychological outcomes, and evidence of protective factors counteracting childhood adversity effects on neurobiology is scarce. We examined the interplay of childhood adversity with protective factors in relation to brain morphology in two independent longitudinal cohorts, the Generation R Study (N = 3008) and the Mannheim Study of Children at Risk (MARS) (N = 179). Cumulative exposure to 12 adverse events was assessed across childhood until age 9 years in Generation R and 11 years in MARS. Protective factors (temperament, cognition, self-esteem, maternal sensitivity, friendship quality) were assessed at various time-points during childhood. Global brain volumes and volumes of amygdala, hippocampus, and the anterior cingulate, medial orbitofrontal and rostral middle frontal cortices were assessed with anatomical scans at 10 years in Generation R and at 25 years in MARS. Childhood adversity was related to smaller cortical grey matter, cerebral white matter, and cerebellar volumes in children. Also, no buffering effects of protective factors on the association between adversity and the brain outcomes survived multiple testing correction. We found no robust evidence for an interaction between protective factors and childhood adversity on broad brain structural measures. Small interaction effects observed in one cohort only warrant further investigation.

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KW - Brain morphology

KW - Child

KW - Magnetic resonance imaging

KW - Resilience

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No robust evidence for an interaction between early-life adversity and protective factors on global and regional brain volumes

Abstract

Bibliographical note

Funding

UN SDGs

Keywords

Access to Document

Persistent URL (handle)

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Cite this