Human Genetics Publications and Presentations
Document Type
Article
Publication Date
7-4-2025
Abstract
Objective
Childhood inhibited temperament (cIT) is associated with an increased risk for developing internalizing psychopathology. Neurobiological characteristics identified by structural magnetic resonance imaging (MRI) may elucidate the neural substrates for cIT, but studies are scarce and often focus on particular regions of interest. Moreover, current findings lack replication. This preregistered analysis from the ENIGMA-Anxiety Working Group examined structural brain characteristics associated with cIT using a comprehensive whole-brain approach.
Method
Temperament assessments (behavioral observations, parent/teacher reports or self-reports on cIT before age 13 years) and MRI data (age at scan, 6-25 years) from international research sites (Europe, North America, South America) were pooled for mega-analysis. Following image processing and quality control, associations between cIT and brain structure were examined in 3,803 participants. Subcortical volumes, cortical thickness, and surface area (main analyses) and detailed subcortical characteristics (eg, subnuclei, subfields, partial volume effects; exploratory analyses) were considered.
Results
In the full sample, cIT showed no relation with brain structure, either as a main effect or in interactions with sex or age. Subgroup analyses (based on cIT assessment type) revealed cIT by sex interactions on mean cortical thickness (pMC-FWER = .037) and thickness of the right superior parietal region (pMC-FWER = .029) in youth with parent/teacher reports on cIT levels. Exploratory analyses revealed findings in the hippocampus, putamen, and caudate, but most did not survive statistical correction for multiple testing.
Conclusion
This mega-analysis found no consistent associations between cIT and regional brain structure, although the role of parietal regions warrants further investigation. Future studies should consider brain function in cIT, preferably using longitudinal designs.
Study Registration Information
Structural Brain Correlates of Childhood Inhibited Temperament: An ENIGMA-Anxiety Mega-analysis. https://www.jaacap.org/article/S0890-8567(22)00299-4/fulltext
Recommended Citation
Bas-Hoogendam, J. M., Bernstein, R. A., Benson, B. E., Frank, S. E. C., Buss, K. A., Gunther, K. E., Pérez-Edgar, K., Salum, G. A., Jackowski, A., Bressan, R. A., Zugman, A., Degnan, K. A., Filippi, C. A., Fox, N. A., Henderson, H. A., Tang, A., Zeytinoglu, S., Harrewijn, A., Hillegers, M. H. J., … Pine, D. S. (2025). Structural Brain Correlates of Childhood Inhibited Temperament: An ENIGMA-Anxiety Mega-Analysis. Journal of the American Academy of Child & Adolescent Psychiatry, 0(0). https://doi.org/10.1016/j.jaac.2025.06.026
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Publication Title
Journal of the American Academy of Child & Adolescent Psychiatry
DOI
10.1016/j.jaac.2025.06.026
Comments
This is an open access article distributed under the terms of the Creative Commons CC-BY license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.