The relationship between brain structure and general psychopathology in preadolescents

Louise Mewton; Briana Lees; Lindsay M. Squeglia; Miriam K. Forbes; Matthew Sunderland; Robert Krueger; Forrest C. Koch; Andrew Baillie; Tim Slade; Nicholas Hoy; Maree Teesson

doi:10.1111/jcpp.13513

The relationship between brain structure and general psychopathology in preadolescents

Louise Mewton, Briana Lees, Lindsay M. Squeglia, Miriam K. Forbes, Matthew Sunderland, Robert Krueger, Forrest C. Koch, Andrew Baillie, Tim Slade, Nicholas Hoy, Maree Teesson

Psychology (Twin Cities)

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

7 Scopus citations

Abstract

Background: An emerging body of literature has indicated that broad, transdiagnostic dimensions of psychopathology are associated with alterations in brain structure across the life span. The current study aimed to investigate the relationship between brain structure and broad dimensions of psychopathology in the critical preadolescent period when psychopathology is emerging. Methods: This study included baseline data from the Adolescent Brain and Cognitive Development (ABCD) Study^® (n = 11,875; age range = 9–10 years; male = 52.2%). General psychopathology, externalizing, internalizing, and thought disorder dimensions were based on a higher-order model of psychopathology and estimated using Bayesian plausible values. Outcome variables included global and regional cortical volume, thickness, and surface area. Results: Higher levels of psychopathology across all dimensions were associated with lower volume and surface area globally, as well as widespread and pervasive alterations across the majority of cortical and subcortical regions studied, after adjusting for sex, race/ethnicity, parental education, income, and maternal psychopathology. The relationships between general psychopathology and brain structure were attenuated when adjusting for cognitive functioning. There were no statistically significant relationships between psychopathology and cortical thickness in this sample of preadolescents. Conclusions: The current study identified lower cortical volume and surface area as transdiagnostic biomarkers for general psychopathology in preadolescence. Future research may focus on whether the widespread and pervasive relationships between general psychopathology and brain structure reflect cognitive dysfunction that is a feature across a range of mental illnesses.

Original language	English (US)
Pages (from-to)	734-744
Number of pages	11
Journal	Journal of Child Psychology and Psychiatry and Allied Disciplines
Volume	63
Issue number	7
Early online date	Sep 1 2021
DOIs	https://doi.org/10.1111/jcpp.13513
State	Published - Sep 1 2021

Bibliographical note

Funding Information:
B.L. is supported by a National Health and Medical Research Council Postgraduate Scholarship (GNT1169377). L.M.S. is supported by the National Institutes of Health (U01 DA041093; K23 AA025399; R01 AA027399). M.K.F. is supported by a Macquarie University Research Fellowship, R.K. is supported in part by the U.S. National Institute on Aging grants R01AG053217 and U19AG051426. Data used in the preparation of this article were obtained from the Adolescent Brain Cognitive Development (ABCD) Study (https://abcdstudy.org), held in the NIMH Data Archive (NDA). This is a multisite, longitudinal study designed to recruit more than 10,000 children aged 9-10 years and follow them over 10 years into early adulthood. The ABCD Study is supported by the National Institutes of Health and additional federal partners ‘under award numbers U01DA041022, U01DA041028, U01DA041048, U01DA041089, U01DA041106, U01DA041117, U01DA041120, U01DA041134, U01DA041148, U01DA041156, U01DA041174, U24DA041123, and U24DA041147’. A full list of supporters is available at https://abcdstudy.org/nih-collaborators. A listing of participating sites and a complete listing of the study investigators can be found at https://abcdstudy.org/principal-investigators.html. ABCD consortium investigators designed and implemented the study and/or provided data but did not necessarily participate in analysis or writing of this report. This manuscript reflects the views of the authors and may not reflect the opinions or views of the NIH or ABCD consortium investigators. The ABCD data repository grows and changes over time. The ABCD data used in this report came from 10.15154/1504431 (DOI). DOIs can be found at https://nda.nih.gov/study.html?id=796. The authors have declared that they have no competing or potential conflicts of interest.Key points This study examined the relationships between brain structure and psychopathology during the critical preadolescent period when mental illness is emerging. Lower global cortical volume and surface area, but not cortical thickness, were identified as transdiagnostic biomarkers of general psychopathology. Some relationships between psychopathology and regional brain structure were attenuated when controlling for cognition, indicating that psychopathology may index cognitive dysfunction. This study examined the relationships between brain structure and psychopathology during the critical preadolescent period when mental illness is emerging. Lower global cortical volume and surface area, but not cortical thickness, were identified as transdiagnostic biomarkers of general psychopathology. Some relationships between psychopathology and regional brain structure were attenuated when controlling for cognition, indicating that psychopathology may index cognitive dysfunction.

Funding Information:
Data used in the preparation of this article were obtained from the Adolescent Brain Cognitive Development (ABCD) Study ( https://abcdstudy.org ), held in the NIMH Data Archive (NDA). This is a multisite, longitudinal study designed to recruit more than 10,000 children aged 9‐10 years and follow them over 10 years into early adulthood. The ABCD Study is supported by the National Institutes of Health and additional federal partners ‘under award numbers U01DA041022, U01DA041028, U01DA041048, U01DA041089, U01DA041106, U01DA041117, U01DA041120, U01DA041134, U01DA041148, U01DA041156, U01DA041174, U24DA041123, and U24DA041147’. A full list of supporters is available at https://abcdstudy.org/nih‐collaborators . A listing of participating sites and a complete listing of the study investigators can be found at https://abcdstudy.org/principal‐investigators.html . ABCD consortium investigators designed and implemented the study and/or provided data but did not necessarily participate in analysis or writing of this report. This manuscript reflects the views of the authors and may not reflect the opinions or views of the NIH or ABCD consortium investigators. The ABCD data repository grows and changes over time. The ABCD data used in this report came from 10.15154/1504431 (DOI). DOIs can be found at https://nda.nih.gov/study.html?id=796 . The authors have declared that they have no competing or potential conflicts of interest. Key points

Funding Information:
B.L. is supported by a National Health and Medical Research Council Postgraduate Scholarship (GNT1169377). L.M.S. is supported by the National Institutes of Health (U01 DA041093; K23 AA025399; R01 AA027399). M.K.F. is supported by a Macquarie University Research Fellowship, R.K. is supported in part by the U.S. National Institute on Aging grants R01AG053217 and U19AG051426.

Publisher Copyright:
© 2021 Association for Child and Adolescent Mental Health.

Keywords

Generalized psychopathology
brain structure
externalizing
internalizing
preadolescence

UN SDGs

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

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10.1111/jcpp.13513

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Mewton, L., Lees, B., Squeglia, L. M., Forbes, M. K., Sunderland, M., Krueger, R., Koch, F. C., Baillie, A., Slade, T., Hoy, N., & Teesson, M. (2021). The relationship between brain structure and general psychopathology in preadolescents. Journal of Child Psychology and Psychiatry and Allied Disciplines, 63(7), 734-744. Advance online publication. https://doi.org/10.1111/jcpp.13513

@article{e3eaee9ae6ee4f61bd8a01efd35ee6a2,

title = "The relationship between brain structure and general psychopathology in preadolescents",

abstract = "Background: An emerging body of literature has indicated that broad, transdiagnostic dimensions of psychopathology are associated with alterations in brain structure across the life span. The current study aimed to investigate the relationship between brain structure and broad dimensions of psychopathology in the critical preadolescent period when psychopathology is emerging. Methods: This study included baseline data from the Adolescent Brain and Cognitive Development (ABCD) Study{\textregistered} (n = 11,875; age range = 9–10 years; male = 52.2%). General psychopathology, externalizing, internalizing, and thought disorder dimensions were based on a higher-order model of psychopathology and estimated using Bayesian plausible values. Outcome variables included global and regional cortical volume, thickness, and surface area. Results: Higher levels of psychopathology across all dimensions were associated with lower volume and surface area globally, as well as widespread and pervasive alterations across the majority of cortical and subcortical regions studied, after adjusting for sex, race/ethnicity, parental education, income, and maternal psychopathology. The relationships between general psychopathology and brain structure were attenuated when adjusting for cognitive functioning. There were no statistically significant relationships between psychopathology and cortical thickness in this sample of preadolescents. Conclusions: The current study identified lower cortical volume and surface area as transdiagnostic biomarkers for general psychopathology in preadolescence. Future research may focus on whether the widespread and pervasive relationships between general psychopathology and brain structure reflect cognitive dysfunction that is a feature across a range of mental illnesses.",

keywords = "Generalized psychopathology, brain structure, externalizing, internalizing, preadolescence",

author = "Louise Mewton and Briana Lees and Squeglia, {Lindsay M.} and Forbes, {Miriam K.} and Matthew Sunderland and Robert Krueger and Koch, {Forrest C.} and Andrew Baillie and Tim Slade and Nicholas Hoy and Maree Teesson",

note = "Funding Information: B.L. is supported by a National Health and Medical Research Council Postgraduate Scholarship (GNT1169377). L.M.S. is supported by the National Institutes of Health (U01 DA041093; K23 AA025399; R01 AA027399). M.K.F. is supported by a Macquarie University Research Fellowship, R.K. is supported in part by the U.S. National Institute on Aging grants R01AG053217 and U19AG051426. Data used in the preparation of this article were obtained from the Adolescent Brain Cognitive Development (ABCD) Study (https://abcdstudy.org), held in the NIMH Data Archive (NDA). This is a multisite, longitudinal study designed to recruit more than 10,000 children aged 9-10 years and follow them over 10 years into early adulthood. The ABCD Study is supported by the National Institutes of Health and additional federal partners {\textquoteleft}under award numbers U01DA041022, U01DA041028, U01DA041048, U01DA041089, U01DA041106, U01DA041117, U01DA041120, U01DA041134, U01DA041148, U01DA041156, U01DA041174, U24DA041123, and U24DA041147{\textquoteright}. A full list of supporters is available at https://abcdstudy.org/nih-collaborators. A listing of participating sites and a complete listing of the study investigators can be found at https://abcdstudy.org/principal-investigators.html. ABCD consortium investigators designed and implemented the study and/or provided data but did not necessarily participate in analysis or writing of this report. This manuscript reflects the views of the authors and may not reflect the opinions or views of the NIH or ABCD consortium investigators. The ABCD data repository grows and changes over time. The ABCD data used in this report came from 10.15154/1504431 (DOI). DOIs can be found at https://nda.nih.gov/study.html?id=796. The authors have declared that they have no competing or potential conflicts of interest.Key points This study examined the relationships between brain structure and psychopathology during the critical preadolescent period when mental illness is emerging. Lower global cortical volume and surface area, but not cortical thickness, were identified as transdiagnostic biomarkers of general psychopathology. Some relationships between psychopathology and regional brain structure were attenuated when controlling for cognition, indicating that psychopathology may index cognitive dysfunction. This study examined the relationships between brain structure and psychopathology during the critical preadolescent period when mental illness is emerging. Lower global cortical volume and surface area, but not cortical thickness, were identified as transdiagnostic biomarkers of general psychopathology. Some relationships between psychopathology and regional brain structure were attenuated when controlling for cognition, indicating that psychopathology may index cognitive dysfunction. Funding Information: Data used in the preparation of this article were obtained from the Adolescent Brain Cognitive Development (ABCD) Study ( https://abcdstudy.org ), held in the NIMH Data Archive (NDA). This is a multisite, longitudinal study designed to recruit more than 10,000 children aged 9‐10 years and follow them over 10 years into early adulthood. The ABCD Study is supported by the National Institutes of Health and additional federal partners {\textquoteleft}under award numbers U01DA041022, U01DA041028, U01DA041048, U01DA041089, U01DA041106, U01DA041117, U01DA041120, U01DA041134, U01DA041148, U01DA041156, U01DA041174, U24DA041123, and U24DA041147{\textquoteright}. A full list of supporters is available at https://abcdstudy.org/nih‐collaborators . A listing of participating sites and a complete listing of the study investigators can be found at https://abcdstudy.org/principal‐investigators.html . ABCD consortium investigators designed and implemented the study and/or provided data but did not necessarily participate in analysis or writing of this report. This manuscript reflects the views of the authors and may not reflect the opinions or views of the NIH or ABCD consortium investigators. The ABCD data repository grows and changes over time. The ABCD data used in this report came from 10.15154/1504431 (DOI). DOIs can be found at https://nda.nih.gov/study.html?id=796 . The authors have declared that they have no competing or potential conflicts of interest. Key points Funding Information: B.L. is supported by a National Health and Medical Research Council Postgraduate Scholarship (GNT1169377). L.M.S. is supported by the National Institutes of Health (U01 DA041093; K23 AA025399; R01 AA027399). M.K.F. is supported by a Macquarie University Research Fellowship, R.K. is supported in part by the U.S. National Institute on Aging grants R01AG053217 and U19AG051426. Publisher Copyright: {\textcopyright} 2021 Association for Child and Adolescent Mental Health.",

year = "2021",

month = sep,

day = "1",

doi = "10.1111/jcpp.13513",

language = "English (US)",

volume = "63",

pages = "734--744",

journal = "Journal of Child Psychology and Psychiatry and Allied Disciplines",

issn = "0021-9630",

publisher = "Wiley-Blackwell",

number = "7",

}

TY - JOUR

T1 - The relationship between brain structure and general psychopathology in preadolescents

AU - Mewton, Louise

AU - Lees, Briana

AU - Squeglia, Lindsay M.

AU - Forbes, Miriam K.

AU - Sunderland, Matthew

AU - Krueger, Robert

AU - Koch, Forrest C.

AU - Baillie, Andrew

AU - Slade, Tim

AU - Hoy, Nicholas

AU - Teesson, Maree

N1 - Funding Information: B.L. is supported by a National Health and Medical Research Council Postgraduate Scholarship (GNT1169377). L.M.S. is supported by the National Institutes of Health (U01 DA041093; K23 AA025399; R01 AA027399). M.K.F. is supported by a Macquarie University Research Fellowship, R.K. is supported in part by the U.S. National Institute on Aging grants R01AG053217 and U19AG051426. Data used in the preparation of this article were obtained from the Adolescent Brain Cognitive Development (ABCD) Study (https://abcdstudy.org), held in the NIMH Data Archive (NDA). This is a multisite, longitudinal study designed to recruit more than 10,000 children aged 9-10 years and follow them over 10 years into early adulthood. The ABCD Study is supported by the National Institutes of Health and additional federal partners ‘under award numbers U01DA041022, U01DA041028, U01DA041048, U01DA041089, U01DA041106, U01DA041117, U01DA041120, U01DA041134, U01DA041148, U01DA041156, U01DA041174, U24DA041123, and U24DA041147’. A full list of supporters is available at https://abcdstudy.org/nih-collaborators. A listing of participating sites and a complete listing of the study investigators can be found at https://abcdstudy.org/principal-investigators.html. ABCD consortium investigators designed and implemented the study and/or provided data but did not necessarily participate in analysis or writing of this report. This manuscript reflects the views of the authors and may not reflect the opinions or views of the NIH or ABCD consortium investigators. The ABCD data repository grows and changes over time. The ABCD data used in this report came from 10.15154/1504431 (DOI). DOIs can be found at https://nda.nih.gov/study.html?id=796. The authors have declared that they have no competing or potential conflicts of interest.Key points This study examined the relationships between brain structure and psychopathology during the critical preadolescent period when mental illness is emerging. Lower global cortical volume and surface area, but not cortical thickness, were identified as transdiagnostic biomarkers of general psychopathology. Some relationships between psychopathology and regional brain structure were attenuated when controlling for cognition, indicating that psychopathology may index cognitive dysfunction. This study examined the relationships between brain structure and psychopathology during the critical preadolescent period when mental illness is emerging. Lower global cortical volume and surface area, but not cortical thickness, were identified as transdiagnostic biomarkers of general psychopathology. Some relationships between psychopathology and regional brain structure were attenuated when controlling for cognition, indicating that psychopathology may index cognitive dysfunction. Funding Information: Data used in the preparation of this article were obtained from the Adolescent Brain Cognitive Development (ABCD) Study ( https://abcdstudy.org ), held in the NIMH Data Archive (NDA). This is a multisite, longitudinal study designed to recruit more than 10,000 children aged 9‐10 years and follow them over 10 years into early adulthood. The ABCD Study is supported by the National Institutes of Health and additional federal partners ‘under award numbers U01DA041022, U01DA041028, U01DA041048, U01DA041089, U01DA041106, U01DA041117, U01DA041120, U01DA041134, U01DA041148, U01DA041156, U01DA041174, U24DA041123, and U24DA041147’. A full list of supporters is available at https://abcdstudy.org/nih‐collaborators . A listing of participating sites and a complete listing of the study investigators can be found at https://abcdstudy.org/principal‐investigators.html . ABCD consortium investigators designed and implemented the study and/or provided data but did not necessarily participate in analysis or writing of this report. This manuscript reflects the views of the authors and may not reflect the opinions or views of the NIH or ABCD consortium investigators. The ABCD data repository grows and changes over time. The ABCD data used in this report came from 10.15154/1504431 (DOI). DOIs can be found at https://nda.nih.gov/study.html?id=796 . The authors have declared that they have no competing or potential conflicts of interest. Key points Funding Information: B.L. is supported by a National Health and Medical Research Council Postgraduate Scholarship (GNT1169377). L.M.S. is supported by the National Institutes of Health (U01 DA041093; K23 AA025399; R01 AA027399). M.K.F. is supported by a Macquarie University Research Fellowship, R.K. is supported in part by the U.S. National Institute on Aging grants R01AG053217 and U19AG051426. Publisher Copyright: © 2021 Association for Child and Adolescent Mental Health.

PY - 2021/9/1

Y1 - 2021/9/1

N2 - Background: An emerging body of literature has indicated that broad, transdiagnostic dimensions of psychopathology are associated with alterations in brain structure across the life span. The current study aimed to investigate the relationship between brain structure and broad dimensions of psychopathology in the critical preadolescent period when psychopathology is emerging. Methods: This study included baseline data from the Adolescent Brain and Cognitive Development (ABCD) Study® (n = 11,875; age range = 9–10 years; male = 52.2%). General psychopathology, externalizing, internalizing, and thought disorder dimensions were based on a higher-order model of psychopathology and estimated using Bayesian plausible values. Outcome variables included global and regional cortical volume, thickness, and surface area. Results: Higher levels of psychopathology across all dimensions were associated with lower volume and surface area globally, as well as widespread and pervasive alterations across the majority of cortical and subcortical regions studied, after adjusting for sex, race/ethnicity, parental education, income, and maternal psychopathology. The relationships between general psychopathology and brain structure were attenuated when adjusting for cognitive functioning. There were no statistically significant relationships between psychopathology and cortical thickness in this sample of preadolescents. Conclusions: The current study identified lower cortical volume and surface area as transdiagnostic biomarkers for general psychopathology in preadolescence. Future research may focus on whether the widespread and pervasive relationships between general psychopathology and brain structure reflect cognitive dysfunction that is a feature across a range of mental illnesses.

AB - Background: An emerging body of literature has indicated that broad, transdiagnostic dimensions of psychopathology are associated with alterations in brain structure across the life span. The current study aimed to investigate the relationship between brain structure and broad dimensions of psychopathology in the critical preadolescent period when psychopathology is emerging. Methods: This study included baseline data from the Adolescent Brain and Cognitive Development (ABCD) Study® (n = 11,875; age range = 9–10 years; male = 52.2%). General psychopathology, externalizing, internalizing, and thought disorder dimensions were based on a higher-order model of psychopathology and estimated using Bayesian plausible values. Outcome variables included global and regional cortical volume, thickness, and surface area. Results: Higher levels of psychopathology across all dimensions were associated with lower volume and surface area globally, as well as widespread and pervasive alterations across the majority of cortical and subcortical regions studied, after adjusting for sex, race/ethnicity, parental education, income, and maternal psychopathology. The relationships between general psychopathology and brain structure were attenuated when adjusting for cognitive functioning. There were no statistically significant relationships between psychopathology and cortical thickness in this sample of preadolescents. Conclusions: The current study identified lower cortical volume and surface area as transdiagnostic biomarkers for general psychopathology in preadolescence. Future research may focus on whether the widespread and pervasive relationships between general psychopathology and brain structure reflect cognitive dysfunction that is a feature across a range of mental illnesses.

KW - Generalized psychopathology

KW - brain structure

KW - externalizing

KW - internalizing

KW - preadolescence

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JF - Journal of Child Psychology and Psychiatry and Allied Disciplines

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ER -

The relationship between brain structure and general psychopathology in preadolescents

Abstract

Bibliographical note

Keywords

UN SDGs

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