Structural brain correlates of childhood trauma with replication across two large, independent community-based samples

Rebecca A Madden; Kimberley Atkinson; Xueyi Shen; Claire Green; Robert F Hillary; Emma Hawkins; Emma Såge; Anca-Larisa Sandu; Gordon Waiter; Christopher McNeil; Mathew Harris; Archie Campbell; David Porteous; Jennifer A Macfarlane; Alison Murray; Douglas Steele; Liana Romaniuk; Stephen M Lawrie; Andrew M McIntosh; Heather C Whalley

doi:10.1192/j.eurpsy.2022.2347

Structural brain correlates of childhood trauma with replication across two large, independent community-based samples

Rebecca A Madden^* (Corresponding Author), Kimberley Atkinson, Xueyi Shen, Claire Green, Robert F Hillary, Emma Hawkins, Emma Såge, Anca-Larisa Sandu, Gordon Waiter, Christopher McNeil, Mathew Harris, Archie Campbell, David Porteous, Jennifer A Macfarlane, Alison Murray, Douglas Steele, Liana Romaniuk, Stephen M Lawrie, Andrew M McIntosh, Heather C Whalley

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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Abstract

Introduction: Childhood trauma and adversity are common across societies and have strong associations with physical and psychiatric morbidity throughout the life-course. One mechanism through which childhood trauma may predispose individuals to poor psychiatric outcomes, such as raised risk of lifetime depression, could be via associations with brain structure. This study aimed to elucidate the associations between childhood trauma scores and brain structure across two large, independent community cohorts.
Methods: The two samples comprised (i) a subsample of individuals from Generation Scotland with imaging and in-depth phenotyping, including the CTQ-28 (n=1,024); and (ii) individuals from UK Biobank with imaging and a modified summary CTQ measure (n=27,202). This comprised n=28,226 for mega-analysis. Scans were processed using FreeSurfer image processing software, providing cortical and subcortical as well as global brain metrics. Regression models were used to determine associations between these metrics and childhood trauma measures. Associations between childhood trauma measures and psychiatric phenotypes were also explored.
Results: Childhood trauma measures associated with lifetime risk of depression diagnosis with similar ORs across cohorts (OR 1.06, 1.23 GS and UKB respectively), which also related to earlier onset and more recurrent course within both samples. There was also evidence for associations between childhood trauma measures and a range of brain structures. Replicated findings included reduced global brain volumes, reduced cortical surface area but not thickness, with highest effects at mega-analysis seen in the frontal (β=-0.0385, SE=0.0048, p(FDR)=5.43x10-15 35 ) and parietal lobes (β=- 0.0387, SE=0.005, p(FDR)=1.56x10-14 36 ). At a regional level, one subcortical regional volume in particular– the ventral diencephalon (VDc) – displayed significant associations with childhood trauma measures across the two cohorts and at mega-analysis (β=-0.0232, SE=0.0039, p(FDR)=2.91x10-8 38 ). There was also evidence for associations with reduced hippocampus, thalamus, and nucleus accumbens volumes, however these were not as consistent across cohorts.
Discussion: There was strong evidence for associations between childhood trauma and reduced global and regional brain volumes across cohorts. In particular, the presence of an association between childhood trauma and the volume of the VDc (which includes the hypothalamic area), with replication, provides further evidence of the importance of neuroendocrine stress response pathways in links between early life stress and clinical outcomes.

Original language	English
Article number	e19
Number of pages	11
Journal	European Psychiatry
Volume	66
Issue number	1
Early online date	26 Jan 2023
DOIs	https://doi.org/10.1192/j.eurpsy.2022.2347
Publication status	Published - 26 Jan 2023

Bibliographical note

Acknowledgments:
The authors thank all individuals and project team members who have contributed to both GS and UKB cohort studies.

Financial support:
GS received core support from the Chief Scientist Office of the Scottish Government Health Directorates (CZD/16/6) and the Scottish Funding Council (HR03006) and is currently supported by the Wellcome Trust [216767/Z/19/Z]. This study was also supported and funded by the Wellcome Trust Strategic Award ‘Stratifying Resilience and Depression Longitudinally’ (STRADL) (Reference 525 104036/Z/14/Z). AMM is supported by the Wellcome Trust (104036/Z/14/Z, 216767/Z/19/Z, 220857/Z/20/Z, 223165/Z/21/Z) and UKRI MRC (MR/W014386/1). This work is part of a project that has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 847776. RAM is supported by funding from the Wellcome Trust 4-year PhD in Translational Neuroscience – training the next generation of basic neuroscientists to embrace clinical research [108890/Z/15/Z].

Data Availability Statement

Data Availability
According to the terms of consent for Generation Scotland participants, access to data must be reviewed by the Generation Scotland Access Committee. Applications should be made to access@generationscotland.org.

Supplementary Materials
To view supplementary material for this article, please visit http://doi.org/10.1192/j.eurpsy.2022.2347.

Keywords

depression
MRI
trauma
adversity
brain

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Madden, R. A., Atkinson, K., Shen, X., Green, C., Hillary, R. F., Hawkins, E., Såge, E., Sandu, A.-L., Waiter, G., McNeil, C., Harris, M., Campbell, A., Porteous, D., Macfarlane, J. A., Murray, A., Steele, D., Romaniuk, L., Lawrie, S. M., McIntosh, A. M., & Whalley, H. C. (2023). Structural brain correlates of childhood trauma with replication across two large, independent community-based samples. European Psychiatry, 66(1), Article e19. https://doi.org/10.1192/j.eurpsy.2022.2347

Madden, RA, Atkinson, K, Shen, X, Green, C, Hillary, RF, Hawkins, E, Såge, E, Sandu, A-L , Waiter, G , McNeil, C, Harris, M, Campbell, A, Porteous, D, Macfarlane, JA, Murray, A, Steele, D, Romaniuk, L, Lawrie, SM, McIntosh, AM & Whalley, HC 2023, 'Structural brain correlates of childhood trauma with replication across two large, independent community-based samples', European Psychiatry, vol. 66, no. 1, e19. https://doi.org/10.1192/j.eurpsy.2022.2347

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title = "Structural brain correlates of childhood trauma with replication across two large, independent community-based samples",

abstract = "Introduction: Childhood trauma and adversity are common across societies and have strong associations with physical and psychiatric morbidity throughout the life-course. One mechanism through which childhood trauma may predispose individuals to poor psychiatric outcomes, such as raised risk of lifetime depression, could be via associations with brain structure. This study aimed to elucidate the associations between childhood trauma scores and brain structure across two large, independent community cohorts.Methods: The two samples comprised (i) a subsample of individuals from Generation Scotland with imaging and in-depth phenotyping, including the CTQ-28 (n=1,024); and (ii) individuals from UK Biobank with imaging and a modified summary CTQ measure (n=27,202). This comprised n=28,226 for mega-analysis. Scans were processed using FreeSurfer image processing software, providing cortical and subcortical as well as global brain metrics. Regression models were used to determine associations between these metrics and childhood trauma measures. Associations between childhood trauma measures and psychiatric phenotypes were also explored.Results: Childhood trauma measures associated with lifetime risk of depression diagnosis with similar ORs across cohorts (OR 1.06, 1.23 GS and UKB respectively), which also related to earlier onset and more recurrent course within both samples. There was also evidence for associations between childhood trauma measures and a range of brain structures. Replicated findings included reduced global brain volumes, reduced cortical surface area but not thickness, with highest effects at mega-analysis seen in the frontal (β=-0.0385, SE=0.0048, p(FDR)=5.43x10-15 35 ) and parietal lobes (β=- 0.0387, SE=0.005, p(FDR)=1.56x10-14 36 ). At a regional level, one subcortical regional volume in particular– the ventral diencephalon (VDc) – displayed significant associations with childhood trauma measures across the two cohorts and at mega-analysis (β=-0.0232, SE=0.0039, p(FDR)=2.91x10-8 38 ). There was also evidence for associations with reduced hippocampus, thalamus, and nucleus accumbens volumes, however these were not as consistent across cohorts.Discussion: There was strong evidence for associations between childhood trauma and reduced global and regional brain volumes across cohorts. In particular, the presence of an association between childhood trauma and the volume of the VDc (which includes the hypothalamic area), with replication, provides further evidence of the importance of neuroendocrine stress response pathways in links between early life stress and clinical outcomes. ",

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author = "Madden, {Rebecca A} and Kimberley Atkinson and Xueyi Shen and Claire Green and Hillary, {Robert F} and Emma Hawkins and Emma S{\aa}ge and Anca-Larisa Sandu and Gordon Waiter and Christopher McNeil and Mathew Harris and Archie Campbell and David Porteous and Macfarlane, {Jennifer A} and Alison Murray and Douglas Steele and Liana Romaniuk and Lawrie, {Stephen M} and McIntosh, {Andrew M} and Whalley, {Heather C}",

note = "Acknowledgments: The authors thank all individuals and project team members who have contributed to both GS and UKB cohort studies. Financial support: GS received core support from the Chief Scientist Office of the Scottish Government Health Directorates (CZD/16/6) and the Scottish Funding Council (HR03006) and is currently supported by the Wellcome Trust [216767/Z/19/Z]. This study was also supported and funded by the Wellcome Trust Strategic Award {\textquoteleft}Stratifying Resilience and Depression Longitudinally{\textquoteright} (STRADL) (Reference 525 104036/Z/14/Z). AMM is supported by the Wellcome Trust (104036/Z/14/Z, 216767/Z/19/Z, 220857/Z/20/Z, 223165/Z/21/Z) and UKRI MRC (MR/W014386/1). This work is part of a project that has received funding from the European Union{\textquoteright}s Horizon 2020 research and innovation programme under grant agreement No 847776. RAM is supported by funding from the Wellcome Trust 4-year PhD in Translational Neuroscience – training the next generation of basic neuroscientists to embrace clinical research [108890/Z/15/Z]. ",

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doi = "10.1192/j.eurpsy.2022.2347",

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T1 - Structural brain correlates of childhood trauma with replication across two large, independent community-based samples

AU - Madden, Rebecca A

AU - Atkinson, Kimberley

AU - Shen, Xueyi

AU - Green, Claire

AU - Hillary, Robert F

AU - Hawkins, Emma

AU - Såge, Emma

AU - Sandu, Anca-Larisa

AU - Waiter, Gordon

AU - McNeil, Christopher

AU - Harris, Mathew

AU - Campbell, Archie

AU - Porteous, David

AU - Macfarlane, Jennifer A

AU - Murray, Alison

AU - Steele, Douglas

AU - Romaniuk, Liana

AU - Lawrie, Stephen M

AU - McIntosh, Andrew M

AU - Whalley, Heather C

N1 - Acknowledgments: The authors thank all individuals and project team members who have contributed to both GS and UKB cohort studies. Financial support: GS received core support from the Chief Scientist Office of the Scottish Government Health Directorates (CZD/16/6) and the Scottish Funding Council (HR03006) and is currently supported by the Wellcome Trust [216767/Z/19/Z]. This study was also supported and funded by the Wellcome Trust Strategic Award ‘Stratifying Resilience and Depression Longitudinally’ (STRADL) (Reference 525 104036/Z/14/Z). AMM is supported by the Wellcome Trust (104036/Z/14/Z, 216767/Z/19/Z, 220857/Z/20/Z, 223165/Z/21/Z) and UKRI MRC (MR/W014386/1). This work is part of a project that has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 847776. RAM is supported by funding from the Wellcome Trust 4-year PhD in Translational Neuroscience – training the next generation of basic neuroscientists to embrace clinical research [108890/Z/15/Z].

PY - 2023/1/26

Y1 - 2023/1/26

N2 - Introduction: Childhood trauma and adversity are common across societies and have strong associations with physical and psychiatric morbidity throughout the life-course. One mechanism through which childhood trauma may predispose individuals to poor psychiatric outcomes, such as raised risk of lifetime depression, could be via associations with brain structure. This study aimed to elucidate the associations between childhood trauma scores and brain structure across two large, independent community cohorts.Methods: The two samples comprised (i) a subsample of individuals from Generation Scotland with imaging and in-depth phenotyping, including the CTQ-28 (n=1,024); and (ii) individuals from UK Biobank with imaging and a modified summary CTQ measure (n=27,202). This comprised n=28,226 for mega-analysis. Scans were processed using FreeSurfer image processing software, providing cortical and subcortical as well as global brain metrics. Regression models were used to determine associations between these metrics and childhood trauma measures. Associations between childhood trauma measures and psychiatric phenotypes were also explored.Results: Childhood trauma measures associated with lifetime risk of depression diagnosis with similar ORs across cohorts (OR 1.06, 1.23 GS and UKB respectively), which also related to earlier onset and more recurrent course within both samples. There was also evidence for associations between childhood trauma measures and a range of brain structures. Replicated findings included reduced global brain volumes, reduced cortical surface area but not thickness, with highest effects at mega-analysis seen in the frontal (β=-0.0385, SE=0.0048, p(FDR)=5.43x10-15 35 ) and parietal lobes (β=- 0.0387, SE=0.005, p(FDR)=1.56x10-14 36 ). At a regional level, one subcortical regional volume in particular– the ventral diencephalon (VDc) – displayed significant associations with childhood trauma measures across the two cohorts and at mega-analysis (β=-0.0232, SE=0.0039, p(FDR)=2.91x10-8 38 ). There was also evidence for associations with reduced hippocampus, thalamus, and nucleus accumbens volumes, however these were not as consistent across cohorts.Discussion: There was strong evidence for associations between childhood trauma and reduced global and regional brain volumes across cohorts. In particular, the presence of an association between childhood trauma and the volume of the VDc (which includes the hypothalamic area), with replication, provides further evidence of the importance of neuroendocrine stress response pathways in links between early life stress and clinical outcomes.

AB - Introduction: Childhood trauma and adversity are common across societies and have strong associations with physical and psychiatric morbidity throughout the life-course. One mechanism through which childhood trauma may predispose individuals to poor psychiatric outcomes, such as raised risk of lifetime depression, could be via associations with brain structure. This study aimed to elucidate the associations between childhood trauma scores and brain structure across two large, independent community cohorts.Methods: The two samples comprised (i) a subsample of individuals from Generation Scotland with imaging and in-depth phenotyping, including the CTQ-28 (n=1,024); and (ii) individuals from UK Biobank with imaging and a modified summary CTQ measure (n=27,202). This comprised n=28,226 for mega-analysis. Scans were processed using FreeSurfer image processing software, providing cortical and subcortical as well as global brain metrics. Regression models were used to determine associations between these metrics and childhood trauma measures. Associations between childhood trauma measures and psychiatric phenotypes were also explored.Results: Childhood trauma measures associated with lifetime risk of depression diagnosis with similar ORs across cohorts (OR 1.06, 1.23 GS and UKB respectively), which also related to earlier onset and more recurrent course within both samples. There was also evidence for associations between childhood trauma measures and a range of brain structures. Replicated findings included reduced global brain volumes, reduced cortical surface area but not thickness, with highest effects at mega-analysis seen in the frontal (β=-0.0385, SE=0.0048, p(FDR)=5.43x10-15 35 ) and parietal lobes (β=- 0.0387, SE=0.005, p(FDR)=1.56x10-14 36 ). At a regional level, one subcortical regional volume in particular– the ventral diencephalon (VDc) – displayed significant associations with childhood trauma measures across the two cohorts and at mega-analysis (β=-0.0232, SE=0.0039, p(FDR)=2.91x10-8 38 ). There was also evidence for associations with reduced hippocampus, thalamus, and nucleus accumbens volumes, however these were not as consistent across cohorts.Discussion: There was strong evidence for associations between childhood trauma and reduced global and regional brain volumes across cohorts. In particular, the presence of an association between childhood trauma and the volume of the VDc (which includes the hypothalamic area), with replication, provides further evidence of the importance of neuroendocrine stress response pathways in links between early life stress and clinical outcomes.

KW - depression

KW - MRI

KW - trauma

KW - adversity

KW - brain

U2 - 10.1192/j.eurpsy.2022.2347

DO - 10.1192/j.eurpsy.2022.2347

M3 - Article

C2 - 36697368

SN - 0924-9338

VL - 66

JO - European Psychiatry

JF - European Psychiatry

IS - 1

M1 - e19

ER -

Structural brain correlates of childhood trauma with replication across two large, independent community-based samples

Abstract

Bibliographical note

Data Availability Statement

Keywords

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