Trajectories of gray and white matter volume in children at elevated risk for schizophrenia
8 affiliations
- 1Department of Psychosis Studies, King’s College London, UK
- 2Center for AI and Data Science for Integrated Diagnostics, and Center for Biomedical Image Computing and Analytics,University of Pennsylvania, USA
- 3Education & Training Division, Anna Freud Centre, UK
- 4Research Department of Clinical, Educational & Health Psychology, University College London, UK
- 5National Institute for Health Research (NIHR), Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London, UK
- 6Division of Insurance Medicine, Department of Clinical Neuroscience, Karolinska Institutet, Sweden
- 7School of Psychology and Counselling, Queensland University of Technology (QUT), Australia
- 8Social, Genetic & Developmental Psychiatry Centre, King’s College London, UK
Abstract
Objective: Longitudinal investigation of brain alterations in children putatively at risk of developing schizophrenia may identify early markers of pathophysiology associated with vulnerability for the disorder.
Methods: Children aged 9–12 years with multiple antecedents of schizophrenia (psychotic-like experiences; speech and/or motor delays; and social, emotional, and/or behavioral difficulties; ASz, n = 31), with a family history of schizophrenia/schizoaffective disorder (FHx, n = 21), and typically developing children (TD, n = 35) were recruited through community screening using questionnaires. T1-weighted structural MRI scans were obtained at baseline and after approximately 2 and 4 years of follow-up, and processed using the FreeSurfer longitudinal pipeline. Across these 3 assessment waves, total gray matter (GM) and white matter (WM) volume, and regional GM volumes in 12 regions of interest, were compared among the groups using linear mixed models.
Results: Children were aged 11.21 (±1.61) years at baseline and the average lapse-of-time between each assessment was 1.76 (±0.36) years. The ASz group exhibited consistently higher total WM volume (b = 29.45) compared to the TD group, with no statistically significant time-related volumetric WM or GM differences in any region. The FHx group also demonstrated higher total WM volume (b = 36.49), and time-related total and regional GM volume changes were observed; however, these effects were attenuated after correction.
Conclusion: Global and regionally specific brain abnormalities distinguished children with different risk profiles for schizophrenia relative to their typically developing peers. Follow-up is required to determine how these changes may relate to later schizophrenia.
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BibTeX
@article{si2026trajectories,
title = {{Trajectories of gray and white matter volume in children at elevated risk for schizophrenia}},
author = {Shuqing Si and Matthew Kempton and Emily Hedges and Mathilde Antoniades and Ruth E. Roberts and Alexis E. Cullen and Kristin R. Laurens},
journal = {CNS Spectrums},
year = {2026},
month = jun,
doi = {10.1017/s1092852926101047},
url = {https://doi.org/10.1017/s1092852926101047},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Trajectories of gray and white matter volume in children at elevated risk for schizophrenia
AU - Shuqing Si
AU - Matthew Kempton
AU - Emily Hedges
AU - Mathilde Antoniades
AU - Ruth E. Roberts
AU - Alexis E. Cullen
AU - Kristin R. Laurens
PY - 2026
DA - 2026/06/09
JO - CNS Spectrums
DO - 10.1017/s1092852926101047
UR - https://doi.org/10.1017/s1092852926101047
AB - Objective: Longitudinal investigation of brain alterations in children putatively at risk of developing schizophrenia may identify early markers of pathophysiology associated with vulnerability for the disorder. Methods: Children aged 9–12 years with multiple antecedents of schizophrenia (psychotic-like experiences; speech and/or motor delays; and social, emotional, and/or behavioral difficulties; ASz, n = 31), with a family history of schizophrenia/schizoaffective disorder (FHx, n = 21), and typically developing children (TD, n = 35) were recruited through community screening using questionnaires. T1-weighted structural MRI scans were obtained at baseline and after approximately 2 and 4 years of follow-up, and processed using the FreeSurfer longitudinal pipeline. Across these 3 assessment waves, total gray matter (GM) and white matter (WM) volume, and regional GM volumes in 12 regions of interest, were compared among the groups using linear mixed models. Results: Children were aged 11.21 (±1.61) years at baseline and the average lapse-of-time between each assessment was 1.76 (±0.36) years. The ASz group exhibited consistently higher total WM volume (b = 29.45) compared to the TD group, with no statistically significant time-related volumetric WM or GM differences in any region. The FHx group also demonstrated higher total WM volume (b = 36.49), and time-related total and regional GM volume changes were observed; however, these effects were attenuated after correction. Conclusion: Global and regionally specific brain abnormalities distinguished children with different risk profiles for schizophrenia relative to their typically developing peers. Follow-up is required to determine how these changes may relate to later schizophrenia.
SN - 1092-8529
SN - 2165-6509
ER -