Journal article
Structural Brain Correlates of Childhood Inhibited Temperament: An ENIGMA-Anxiety Mega-Analysis
Journal of the American Academy of Child and Adolescent Psychiatry, Vol.65(4), pp.577-604
04/01/2026
DOI: 10.1016/j.jaac.2025.06.026
PMCID: PMC12321241
PMID: 40619094
Abstract
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.
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.
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.
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.
Inhibited temperament during childhood is a risk factor for the development of anxiety and depression later in life. A preregistered study from the international ENIGMA-Anxiety Working Group investigated whether characteristics of brain structure are associated with the level of childhood inhibited temperament, using brain scans and data on temperamental traits from participants aged 6 to 25 years, which have been previously acquired at research sites worldwide (total sample > 3,800 subjects). Analyses revealed no consistent correlations between brain structure and inhibited temperament.
Structural Brain Correlates of Childhood Inhibited Temperament: An ENIGMA-Anxiety Mega-analysis. https://www.jaacap.org/article/S0890-8567(22)00299-4/fulltext
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Details
- Title: Subtitle
- Structural Brain Correlates of Childhood Inhibited Temperament: An ENIGMA-Anxiety Mega-Analysis
- Creators
- Janna Marie Bas-Hoogendam - Leiden UniversityRachel A. Bernstein - National Institute of Mental HealthBrenda E. Benson - National Institute of Mental HealthSamuel E.C. Frank - National Institute of Mental Health, Bethesda, MarylandKristin A. Buss - Pennsylvania State UniversityKelley E. Gunther - Pennsylvania State UniversityKoraly Pérez-Edgar - Pennsylvania State UniversityGiovanni A. Salum - Universidade Federal do Rio Grande do SulAndrea Jackowski - Universidade Federal de São PauloRodrigo A. Bressan - Universidade Federal de São PauloAndré Zugman - National Institute of Mental HealthKathryn A. Degnan - Catholic University of AmericaCourtney A. Filippi - New York UniversityNathan A. Fox - University of Maryland, College ParkHeather A. Henderson - University of WaterlooAlva Tang - The University of Texas at DallasSelin Zeytinoglu - Tulane UniversityAnita Harrewijn - Erasmus University RotterdamManon H.J. Hillegers - Erasmus MCRyan L. Muetzel - Erasmus MCTonya White - Erasmus MCMarinus H. van IJzendoorn - San Sebastián UniversityCarl E. Schwartz - Harvard UniversityJulia M. Felicione - Tufts UniversityKathryn A. DeYoung - University of Maryland, College ParkAlexander J. Shackman - University of Maryland, College ParkJason F. Smith - University of Maryland, College ParkRachael M. Tillman - University of Maryland, College ParkYvonne H.M. van den Berg - Radboud University NijmegenAntonius H.N. Cillessen - Radboud University NijmegenKarin Roelofs - Radboud University NijmegenAnna Tyborowska - Radboud University NijmegenShirley Y. Hill - University of PittsburghMarco Battaglia - Centre for Addiction and Mental HealthMarco Tettamanti - University of Milano-BicoccaLea R. Dougherty - University of Maryland, College ParkJingwen Jin - University of Hong KongDaniel N. Klein - Stony Brook UniversityHoi-Chung Leung - Stony Brook UniversitySuzanne N. Avery - Vanderbilt University Medical CenterJennifer Urbano Blackford - Nebraska Medical CenterJacqueline A. Clauss - University of Maryland, BaltimoreJames M. Bjork - Virginia Commonwealth UniversityJohn M. Hettema - Bryan CollegeAshlee A. Moore - State University of New York at OswegoRoxann Roberson-Nay - University of VirginiaChelsea Sawyers - Virginia Commonwealth UniversityElizabeth P. Hayden - Western UniversityPan Liu - Western UniversityMatthew R.J. Vandermeer - Western UniversityH. Hill Goldsmith - University of Wisconsin–MadisonElizabeth M. Planalp - University of Wisconsin–MadisonThomas E. Nichols - University of OxfordPaul M. Thompson - University of Southern CaliforniaP. Michiel Westenberg - Leiden UniversityNic J.A. van der Wee - Leiden University Medical CenterNynke A. Groenewold - University of Cape TownDan J. Stein - University of Cape TownAnderson M. Winkler - The University of Texas Rio Grande ValleyDaniel S. Pine - National Institute of Mental Health
- Resource Type
- Journal article
- Publication Details
- Journal of the American Academy of Child and Adolescent Psychiatry, Vol.65(4), pp.577-604
- DOI
- 10.1016/j.jaac.2025.06.026
- PMID
- 40619094
- PMCID
- PMC12321241
- NLM abbreviation
- J Am Acad Child Adolesc Psychiatry
- ISSN
- 0890-8567
- eISSN
- 1527-5418
- Publisher
- Elsevier Inc
- Number of pages
- 28
- Language
- English
- Date published
- 04/01/2026
- Academic Unit
- Psychiatry
- Record Identifier
- 9985222823902771
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