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Exploring the course of adolescent anxiety and depression: associations with white matter tract microstructure

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Abstract

Cross-sectional Diffusion Tensor Imaging (DTI) studies have reported alterations in white matter (WM) microstructure in adolescents with internalizing psychopathology. Yet, longitudinal studies investigating the course of WM microstructure are lacking. This study explored WM alterations and its relation to clinical symptoms over time in adolescents with internalizing disorders. DTI scans were acquired at baseline and after three months in 22 adolescents with clinical depression and comorbid anxiety (INT), and 21 healthy peers (HC) (age: 12–18). Tract-based spatial statistics was used for three voxelwise analyses: i) changes in WM microstructure between and within the INT and HC group; ii) associations between changes in symptom severity and changes in WM microstructure within youths with INT; and iii) associations between baseline WM parameters with changes in symptom severity within youths with INT. Data did not reveal changes in WM microstructure between or within groups over three months’ time nor associations between changes in WM microstructure and changes in self-reported symptoms (analyses corrected for age, gender and puberty stage). Lower baseline levels of fractional anisotropy (FA) in the right posterior corona radiata (PCR) and right cingulum were associated with a higher decrease of depressive symptoms within the INT group. Post hoc analysis of additional WM parameters in the significant FA clusters showed that higher levels of baseline mean diffusivity and radial diffusivity in the PCR were associated with a lower decrease in depressive symptoms. Baseline WM microstructure characteristics were associated with a higher decrease in depressive symptoms over time. These findings increase our understanding of neurobiological mechanisms underlying the course of internalizing disorders in adolescents.

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Funding

We thank the following participating centers for financial support: Department of Child and Adolescent Psychiatry of GGZ Rivierduinen, the LUMC Departments of Psychiatry and Radiology, and the Leiden Institute for Brain and Cognition.

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Authors and Affiliations

  1. Department of Child and Adolescent Psychiatry, Curium-LUMC, Leiden University Medical Center, Leiden, The Netherlands

    Eline F. Roelofs, Saskia D. Valstar & Robert R. J. M. Vermeiren

  2. Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands

    Eline F. Roelofs, Janna Marie Bas-Hoogendam, Steven J. A. van der Werff & Nic J. A. van der Wee

  3. Leiden Institute for Brain and Cognition, Leiden, The Netherlands

    Eline F. Roelofs, Janna Marie Bas-Hoogendam, Steven J. A. van der Werff, Nic J. A. van der Wee & Robert R. J. M. Vermeiren

  4. Developmental and Educational Psychology, Institute of Psychology, Leiden University, Leiden, The Netherlands

    Janna Marie Bas-Hoogendam

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  1. Eline F. Roelofs
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  2. Janna Marie Bas-Hoogendam
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  3. Steven J. A. van der Werff
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Contributions

Eline F. Roelofs: Methodology, Software, Formal analysis, Data curation, Writing—original draft, Visualization. Janna Marie Bas-Hoogendam: Methodology, Supervision, Writing—review and editing. Steven J.A. van der Werff: Methodology, Writing—review and editing. Saskia D. Valstar: Formal analysis, Writing—review and editing. Nic J.A. van der Wee: Conceptualization, Funding acquisition, Investigation, Methodology, Resources, Supervision, Writing—review and editing. Robert R.J.M. Vermeiren: Conceptualization, Funding acquisition, Investigation, Methodology, Resources, Supervision, Writing—review and editing.

Corresponding author

Correspondence to Eline F. Roelofs.

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The authors report no biomedical financial interests or potential conflicts of interest.

Ethics approval

The EPISCA study was approved by the medical ethics committee of Leiden University Medical Center.

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All participants provided informed consent according to the Declaration of Helsinki; both participants and parents signed the informed consent form. All anatomical scans were reviewed by a radiologist.

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Roelofs, E.F., Bas-Hoogendam, J.M., van der Werff, S.J.A. et al. Exploring the course of adolescent anxiety and depression: associations with white matter tract microstructure. Eur Arch Psychiatry Clin Neurosci 272, 849–858 (2022). https://doi.org/10.1007/s00406-021-01347-8

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  • DOI: https://doi.org/10.1007/s00406-021-01347-8

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