The non-specific nature of mental health and structural brain outcomes following childhood trauma

Theresa K. Haidl; Dennis M. Hedderich; Marlene Rosen; Nathalie Kaiser; Mauro Seves; Thorsten Lichtenstein; Nora Penzel; Julian Wenzel; Lana Kambeitz-ilankovic; Anne Ruef; David Popovic; Frauke Schultze-lutter; Katharine Chisholm; Rachel Upthegrove; Raimo K. R. Salokangas; Christos Pantelis; Eva Meisenzahl; Stephen J. Wood; Paolo Brambilla; Stefan Borgwardt; Stephan Ruhrmann; Joseph Kambeitz; Nikolaos Koutsouleris

doi:10.1017/S0033291721002439

The non-specific nature of mental health and structural brain outcomes following childhood trauma

Theresa K. Haidl^*, Dennis M. Hedderich, Marlene Rosen, Nathalie Kaiser, Mauro Seves, Thorsten Lichtenstein, Nora Penzel, Julian Wenzel, Lana Kambeitz-ilankovic, Anne Ruef, David Popovic, Frauke Schultze-lutter, Katharine Chisholm, Rachel Upthegrove, Raimo K. R. Salokangas, Christos Pantelis, Eva Meisenzahl, Stephen J. Wood, Paolo Brambilla, Stefan BorgwardtStephan Ruhrmann, Joseph Kambeitz, Nikolaos Koutsouleris

^*Corresponding author for this work

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

Abstract

Background: Childhood trauma (CT) is associated with an increased risk of mental health disorders; however, it is unknown whether this represents a diagnosis-specific risk factor for specific psychopathology mediated by structural brain changes. Our aim was to explore whether (i) a predictive CT pattern for transdiagnostic psychopathology exists, and whether (ii) CT can differentiate between distinct diagnosis-dependent psychopathology. Furthermore, we aimed to identify the association between CT, psychopathology and brain structure.

Methods: We used multivariate pattern analysis in data from 643 participants of the Personalised Prognostic Tools for Early Psychosis Management study (PRONIA), including healthy controls (HC), recent onset psychosis (ROP), recent onset depression (ROD), and patients clinically at high-risk for psychosis (CHR). Participants completed structured interviews and self-report measures including the Childhood Trauma Questionnaire, SCID diagnostic interview, BDI-II, PANSS, Schizophrenia Proneness Instrument, Structured Interview for Prodromal Symptoms and structural MRI, analyzed by voxel-based morphometry.

Results: (i) Patients and HC could be distinguished by their CT pattern with a reasonable precision [balanced accuracy of 71.2% (sensitivity = 72.1%, specificity = 70.4%, p ≤ 0.001]. (ii) Subdomains 'emotional neglect' and 'emotional abuse' were most predictive for CHR and ROP, while in ROD 'physical abuse' and 'sexual abuse' were most important. The CT pattern was significantly associated with the severity of depressive symptoms in ROD, ROP, and CHR, as well as with the PANSS total and negative domain scores in the CHR patients. No associations between group-separating CT patterns and brain structure were found.

Conclusions: These results indicate that CT poses a transdiagnostic risk factor for mental health disorders, possibly related to depressive symptoms. While differences in the quality of CT exposure exist, diagnostic differentiation was not possible suggesting a multi-factorial pathogenesis.

Original language	English
Pages (from-to)	1005-1014
Number of pages	10
Journal	Psychological Medicine
Volume	53
Issue number	3
Early online date	6 Jul 2021
DOIs	https://doi.org/10.1017/S0033291721002439
Publication status	Published - 6 Feb 2023

Bibliographical note

Copyright © The Author(s), 2021. Published by Cambridge University Press.

Funding: PRONIA is a Collaborative Project funded by the European Union under the 7th Framework Programme under grant agreement n° 602152. R.U. reports grants from Medical Research Council, grants from the National Institute for Health Research, and personal fees from Sunovion, outside the submitted work. N.K. and R.S. received honoraria for talks presented at education meetings organized by Otsuka/Lundbeck. C.P. participated in advisory boards for Janssen-Cilag, AstraZeneca, Lundbeck, and Servier and received honoraria for talks presented at educational meetings organized by AstraZeneca, Janssen-Cilag, Eli Lilly, Pfizer, Lundbeck, and Shire. C.P. acknowledges support by an Australian National Health & Medical Research Council (NHMRC) Senior Principal Research Fellowship (ID: 1105825), an NHMRC Program Grant (ID: 1150083). J.K. reports funding by the DFG (KA 4413/1-1) and received honoraria for talks presented at educational meetings organized by Janssen and Otsuka/Lundbeck.

Keywords

Brain structure
childhood maltreatment
emotional abuse
emotional neglect
multivariate pattern analysis
physical abuse
sexual abuse

Access to Document

10.1017/S0033291721002439

Cite this

Haidl, T. K., Hedderich, D. M., Rosen, M., Kaiser, N., Seves, M., Lichtenstein, T., Penzel, N., Wenzel, J., Kambeitz-ilankovic, L., Ruef, A., Popovic, D., Schultze-lutter, F., Chisholm, K., Upthegrove, R., Salokangas, R. K. R., Pantelis, C., Meisenzahl, E., Wood, S. J., Brambilla, P., ... Koutsouleris, N. (2023). The non-specific nature of mental health and structural brain outcomes following childhood trauma. Psychological Medicine, 53(3), 1005-1014. https://doi.org/10.1017/S0033291721002439

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title = "The non-specific nature of mental health and structural brain outcomes following childhood trauma",

abstract = "Background: Childhood trauma (CT) is associated with an increased risk of mental health disorders; however, it is unknown whether this represents a diagnosis-specific risk factor for specific psychopathology mediated by structural brain changes. Our aim was to explore whether (i) a predictive CT pattern for transdiagnostic psychopathology exists, and whether (ii) CT can differentiate between distinct diagnosis-dependent psychopathology. Furthermore, we aimed to identify the association between CT, psychopathology and brain structure.Methods: We used multivariate pattern analysis in data from 643 participants of the Personalised Prognostic Tools for Early Psychosis Management study (PRONIA), including healthy controls (HC), recent onset psychosis (ROP), recent onset depression (ROD), and patients clinically at high-risk for psychosis (CHR). Participants completed structured interviews and self-report measures including the Childhood Trauma Questionnaire, SCID diagnostic interview, BDI-II, PANSS, Schizophrenia Proneness Instrument, Structured Interview for Prodromal Symptoms and structural MRI, analyzed by voxel-based morphometry.Results: (i) Patients and HC could be distinguished by their CT pattern with a reasonable precision [balanced accuracy of 71.2% (sensitivity = 72.1%, specificity = 70.4%, p ≤ 0.001]. (ii) Subdomains 'emotional neglect' and 'emotional abuse' were most predictive for CHR and ROP, while in ROD 'physical abuse' and 'sexual abuse' were most important. The CT pattern was significantly associated with the severity of depressive symptoms in ROD, ROP, and CHR, as well as with the PANSS total and negative domain scores in the CHR patients. No associations between group-separating CT patterns and brain structure were found.Conclusions: These results indicate that CT poses a transdiagnostic risk factor for mental health disorders, possibly related to depressive symptoms. While differences in the quality of CT exposure exist, diagnostic differentiation was not possible suggesting a multi-factorial pathogenesis.",

keywords = "Brain structure, childhood maltreatment, emotional abuse, emotional neglect, multivariate pattern analysis, physical abuse, sexual abuse",

author = "Haidl, {Theresa K.} and Hedderich, {Dennis M.} and Marlene Rosen and Nathalie Kaiser and Mauro Seves and Thorsten Lichtenstein and Nora Penzel and Julian Wenzel and Lana Kambeitz-ilankovic and Anne Ruef and David Popovic and Frauke Schultze-lutter and Katharine Chisholm and Rachel Upthegrove and Salokangas, {Raimo K. R.} and Christos Pantelis and Eva Meisenzahl and Wood, {Stephen J.} and Paolo Brambilla and Stefan Borgwardt and Stephan Ruhrmann and Joseph Kambeitz and Nikolaos Koutsouleris",

note = "Copyright {\textcopyright} The Author(s), 2021. Published by Cambridge University Press. Funding: PRONIA is a Collaborative Project funded by the European Union under the 7th Framework Programme under grant agreement n° 602152. R.U. reports grants from Medical Research Council, grants from the National Institute for Health Research, and personal fees from Sunovion, outside the submitted work. N.K. and R.S. received honoraria for talks presented at education meetings organized by Otsuka/Lundbeck. C.P. participated in advisory boards for Janssen-Cilag, AstraZeneca, Lundbeck, and Servier and received honoraria for talks presented at educational meetings organized by AstraZeneca, Janssen-Cilag, Eli Lilly, Pfizer, Lundbeck, and Shire. C.P. acknowledges support by an Australian National Health & Medical Research Council (NHMRC) Senior Principal Research Fellowship (ID: 1105825), an NHMRC Program Grant (ID: 1150083). J.K. reports funding by the DFG (KA 4413/1-1) and received honoraria for talks presented at educational meetings organized by Janssen and Otsuka/Lundbeck.",

year = "2023",

month = feb,

day = "6",

doi = "10.1017/S0033291721002439",

language = "English",

volume = "53",

pages = "1005--1014",

journal = "Psychological Medicine",

issn = "0033-2917",

publisher = "Cambridge University Press",

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Haidl, TK, Hedderich, DM, Rosen, M, Kaiser, N, Seves, M, Lichtenstein, T, Penzel, N, Wenzel, J, Kambeitz-ilankovic, L, Ruef, A, Popovic, D, Schultze-lutter, F, Chisholm, K, Upthegrove, R, Salokangas, RKR, Pantelis, C, Meisenzahl, E, Wood, SJ, Brambilla, P, Borgwardt, S, Ruhrmann, S, Kambeitz, J & Koutsouleris, N 2023, 'The non-specific nature of mental health and structural brain outcomes following childhood trauma', Psychological Medicine, vol. 53, no. 3, pp. 1005-1014. https://doi.org/10.1017/S0033291721002439

TY - JOUR

T1 - The non-specific nature of mental health and structural brain outcomes following childhood trauma

AU - Haidl, Theresa K.

AU - Hedderich, Dennis M.

AU - Rosen, Marlene

AU - Kaiser, Nathalie

AU - Seves, Mauro

AU - Lichtenstein, Thorsten

AU - Penzel, Nora

AU - Wenzel, Julian

AU - Kambeitz-ilankovic, Lana

AU - Ruef, Anne

AU - Popovic, David

AU - Schultze-lutter, Frauke

AU - Chisholm, Katharine

AU - Upthegrove, Rachel

AU - Salokangas, Raimo K. R.

AU - Pantelis, Christos

AU - Meisenzahl, Eva

AU - Wood, Stephen J.

AU - Brambilla, Paolo

AU - Borgwardt, Stefan

AU - Ruhrmann, Stephan

AU - Kambeitz, Joseph

AU - Koutsouleris, Nikolaos

N1 - Copyright © The Author(s), 2021. Published by Cambridge University Press. Funding: PRONIA is a Collaborative Project funded by the European Union under the 7th Framework Programme under grant agreement n° 602152. R.U. reports grants from Medical Research Council, grants from the National Institute for Health Research, and personal fees from Sunovion, outside the submitted work. N.K. and R.S. received honoraria for talks presented at education meetings organized by Otsuka/Lundbeck. C.P. participated in advisory boards for Janssen-Cilag, AstraZeneca, Lundbeck, and Servier and received honoraria for talks presented at educational meetings organized by AstraZeneca, Janssen-Cilag, Eli Lilly, Pfizer, Lundbeck, and Shire. C.P. acknowledges support by an Australian National Health & Medical Research Council (NHMRC) Senior Principal Research Fellowship (ID: 1105825), an NHMRC Program Grant (ID: 1150083). J.K. reports funding by the DFG (KA 4413/1-1) and received honoraria for talks presented at educational meetings organized by Janssen and Otsuka/Lundbeck.

PY - 2023/2/6

Y1 - 2023/2/6

N2 - Background: Childhood trauma (CT) is associated with an increased risk of mental health disorders; however, it is unknown whether this represents a diagnosis-specific risk factor for specific psychopathology mediated by structural brain changes. Our aim was to explore whether (i) a predictive CT pattern for transdiagnostic psychopathology exists, and whether (ii) CT can differentiate between distinct diagnosis-dependent psychopathology. Furthermore, we aimed to identify the association between CT, psychopathology and brain structure.Methods: We used multivariate pattern analysis in data from 643 participants of the Personalised Prognostic Tools for Early Psychosis Management study (PRONIA), including healthy controls (HC), recent onset psychosis (ROP), recent onset depression (ROD), and patients clinically at high-risk for psychosis (CHR). Participants completed structured interviews and self-report measures including the Childhood Trauma Questionnaire, SCID diagnostic interview, BDI-II, PANSS, Schizophrenia Proneness Instrument, Structured Interview for Prodromal Symptoms and structural MRI, analyzed by voxel-based morphometry.Results: (i) Patients and HC could be distinguished by their CT pattern with a reasonable precision [balanced accuracy of 71.2% (sensitivity = 72.1%, specificity = 70.4%, p ≤ 0.001]. (ii) Subdomains 'emotional neglect' and 'emotional abuse' were most predictive for CHR and ROP, while in ROD 'physical abuse' and 'sexual abuse' were most important. The CT pattern was significantly associated with the severity of depressive symptoms in ROD, ROP, and CHR, as well as with the PANSS total and negative domain scores in the CHR patients. No associations between group-separating CT patterns and brain structure were found.Conclusions: These results indicate that CT poses a transdiagnostic risk factor for mental health disorders, possibly related to depressive symptoms. While differences in the quality of CT exposure exist, diagnostic differentiation was not possible suggesting a multi-factorial pathogenesis.

AB - Background: Childhood trauma (CT) is associated with an increased risk of mental health disorders; however, it is unknown whether this represents a diagnosis-specific risk factor for specific psychopathology mediated by structural brain changes. Our aim was to explore whether (i) a predictive CT pattern for transdiagnostic psychopathology exists, and whether (ii) CT can differentiate between distinct diagnosis-dependent psychopathology. Furthermore, we aimed to identify the association between CT, psychopathology and brain structure.Methods: We used multivariate pattern analysis in data from 643 participants of the Personalised Prognostic Tools for Early Psychosis Management study (PRONIA), including healthy controls (HC), recent onset psychosis (ROP), recent onset depression (ROD), and patients clinically at high-risk for psychosis (CHR). Participants completed structured interviews and self-report measures including the Childhood Trauma Questionnaire, SCID diagnostic interview, BDI-II, PANSS, Schizophrenia Proneness Instrument, Structured Interview for Prodromal Symptoms and structural MRI, analyzed by voxel-based morphometry.Results: (i) Patients and HC could be distinguished by their CT pattern with a reasonable precision [balanced accuracy of 71.2% (sensitivity = 72.1%, specificity = 70.4%, p ≤ 0.001]. (ii) Subdomains 'emotional neglect' and 'emotional abuse' were most predictive for CHR and ROP, while in ROD 'physical abuse' and 'sexual abuse' were most important. The CT pattern was significantly associated with the severity of depressive symptoms in ROD, ROP, and CHR, as well as with the PANSS total and negative domain scores in the CHR patients. No associations between group-separating CT patterns and brain structure were found.Conclusions: These results indicate that CT poses a transdiagnostic risk factor for mental health disorders, possibly related to depressive symptoms. While differences in the quality of CT exposure exist, diagnostic differentiation was not possible suggesting a multi-factorial pathogenesis.

KW - Brain structure

KW - childhood maltreatment

KW - emotional abuse

KW - emotional neglect

KW - multivariate pattern analysis

KW - physical abuse

KW - sexual abuse

UR - https://www.cambridge.org/core/product/identifier/S0033291721002439/type/journal_article

UR - http://www.scopus.com/inward/record.url?scp=85109318002&partnerID=8YFLogxK

U2 - 10.1017/S0033291721002439

DO - 10.1017/S0033291721002439

M3 - Article

SN - 0033-2917

VL - 53

SP - 1005

EP - 1014

JO - Psychological Medicine

JF - Psychological Medicine

IS - 3

ER -

The non-specific nature of mental health and structural brain outcomes following childhood trauma

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Keywords

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