White Matter Microstructure and the General Psychopathology Factor in Children

Alexander Neumann, Ryan L. Muetzel, Benjamin B. Lahey, Marian J. Bakermans-Kranenburg, Marinus H. van IJzendoorn, Vincent W. Jaddoe, Manon H.J. Hillegers, Tonya White, Henning Tiemeier*

*Corresponding author for this work

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Abstract

Objective: Co-occurrence of behavioral and emotional problems in childhood is widespread, and previous studies have suggested that this reflects vulnerability to experience a range of psychiatric problems, often termed a general psychopathology factor. However, the neurobiological substrate of this general factor is not well understood. We tested the hypothesis that lower overall white matter microstructure is associated with higher levels of the general psychopathology factor in children and less with specific factors. Method: Global white matter microstructure at age 10 years was related to general and specific psychopathology factors. These factors were estimated using a latent bifactor model with multiple informants and instruments between ages 6 and 10 years in 3,030 children from the population-based birth cohort Generation R. The association of global white matter microstructure and the psychopathology factors was examined with a structural equation model adjusted for sex, age at scan, age at psychopathology assessment, parental education/income, and genetic ancestry. Results: A 1-SD increase of the global white matter factor was associated with a β = −0.07SD (standard error [SE] = 0.02, p < .01) decrease in general psychopathology. In contrast, a 1-SD increase of white matter microstructure predicted an increase of β = +0.07 SD (SE = 0.03, p < .01) specific externalizing factor levels. No association was found with the specific internalizing and specific attention factor. Conclusion: The results suggest that general psychopathology in childhood is related to white matter structure across the brain and not only to specific tracts. Taking into account general psychopathology may also help reveal neurobiological mechanisms behind specific symptoms that are otherwise obscured by comorbidity.

Original languageEnglish
Pages (from-to)1285-1296
Number of pages12
JournalJournal of the American Academy of Child and Adolescent Psychiatry
Volume59
Issue number11
Early online date23 Jan 2020
DOIs
Publication statusPublished - Nov 2020

Funding

The Generation R Study is made possible by financial support from the Erasmus Medical Center, Rotterdam and the Netherlands Organization for Health Research and Development (ZonMw). The neuroimaging infrastructure is supported by ZonMw TOP (No: 91211021), the NWO Physical Sciences Division (Exacte Wetenschappen), and SURFsara supercomputing center (Cartesius Compute Cluster). Disclosure: Dr. Neumann has received grant support from the Dutch Ministry of Education, Culture, and Science and the Netherlands Organization for Scientific Research (NWO grant No. 024.001.003 , Consortium on Individual Development), as well as a Canadian Institutes of Health Research team grant. Dr. Bakermans-Kranenburg has received support from the Netherlands Organization for Scientific Research (SPINOZA, VICI) and the European Research Council (AdG 669249). Dr. van IJzendoorn has received support from the Netherlands Organization for Scientific Research (SPINOZA, VICI). Dr. White has received grant or research support from the Sophia Children’s Hospital Foundation , the Simons Foundation Autism Research Initiative , and the Netherlands Organisation for Health Research and Development (ZonMw). She has served on the editorial board of Neuroinformatics and is guest editing an edition on Neuroimaging in the Global Context in NeuroImage. Dr. Tiemeier has received grant support from the Dutch Ministry of Education, Culture, and Science and the Netherlands Organization for Scientific Research (NWO grant No. 024.001.003, Consortium on Individual Development) and NWO-VICI (NWOZonMW: 016.VICI.170.200). Drs. Muetzel, Lahey, Jaddoe, and Hillegers have reported no biomedical financial interests or potential conflicts of interest.

FundersFunder number
Dutch Ministry of Education, Culture, and Science
Erasmus Medical Center, Rotterdam
NWO Physical Sciences Division
NWO-VICI
SPINOZA
Sophia Children’s Hospital Foundation
ZonMw TOP91211021
Children's Hospital Foundation
Simons Foundation Autism Research Initiative
Canadian Institutes of Health Research
European Research CouncilAdG 669249
ZonMw
Nederlandse Organisatie voor Wetenschappelijk Onderzoek024.001.003

    Keywords

    • attention
    • externalizing disorder
    • internalizing disorder
    • magnetic resonance imaging
    • structural equation modeling

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