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Record W4412031490 · doi:10.1016/j.jaac.2025.06.026

Structural Brain Correlates of Childhood Inhibited Temperament: An ENIGMA-Anxiety Mega-Analysis

2025· article· en· W4412031490 on OpenAlexafffund
Janna Marie Bas‐Hoogendam, Rachel Bernstein, Brenda E. Benson, Samuel Frank, Kristin A. Buss, Kelley E. Gunther, Koraly Pérez‐Edgar, Giovanni Abrahão Salum, Andrea Parolin Jackowski, Rodrigo A. Bressan, André Zugman, Kathryn A. Degnan, Courtney A. Filippi, Nathan A. Fox, Heather A. Henderson, Alva Tang, Selin Zeytinoglu, Anita Harrewijn, Manon H. J. Hillegers, Ryan L. Muetzel, Tonya White, Marinus H. van IJzendoorn, C. Schwartz, Julia M. Felicione, Kathryn A. DeYoung, Alexander J. Shackman, Jason F. Smith, Rachael M. Tillman, Yvonne H. M. van den Berg, Antonius H. N. Cillessen, Karin Roelofs, Anna Tyborowska, Shirley Y. Hill, Marco Battaglia, Marco Tettamanti, Lea R. Dougherty, Jingwen Jin, Daniel N. Klein, Hoi‐Chung Leung, Suzanne N. Avery, Jennifer Urbano Blackford, Jacqueline A. Clauss, James M. Bjork, John M. Hettema, Ashlee A. Moore, Roxann Roberson‐Nay, Chelsea Sawyers, Elizabeth P. Hayden, Pan Liu, Matthew R.J. Vandermeer, H. Hill Goldsmith, Elizabeth M. Planalp, Thomas E. Nichols, Paul M. Thompson, P. Michiel Westenberg, Nic J.A. van der Wee, Nynke A. Groenewold, Dan J. Stein, Anderson M. Winkler, Daniel S. Pine

Bibliographic record

VenueJournal of the American Academy of Child & Adolescent Psychiatry · 2025
Typearticle
Languageen
FieldPsychology
TopicChild and Adolescent Psychosocial and Emotional Development
Canadian institutionsUniversity of AlbertaWestern UniversityCentre for Addiction and Mental HealthUniversity of Waterloo
FundersHORIZON EUROPE Marie Sklodowska-Curie ActionsFP7 HealthH2020 Marie Skłodowska-Curie ActionsNational Institute on Drug AbuseNational Institute on Alcohol Abuse and AlcoholismNational Institute of Environmental Health SciencesEuropean Research CouncilCanadian Institutes of Health ResearchNational Institute of Mental HealthSocial Sciences and Humanities Research Council of CanadaHorizon 2020 Framework ProgrammeNational Institutes of HealthUniversity of Texas Rio Grande ValleyMedical DeltaH. Lundbeck A/SMedical Research CouncilServierInnovative Medicines InitiativeMedical Research Council CanadaWaisman CenterErasmus Universiteit RotterdamEuropean College of NeuropsychopharmacologyCanada First Research Excellence FundUniversity of Cape TownBrain and Behavior Research FoundationCanada Foundation for InnovationConselho Nacional de Desenvolvimento Científico e TecnológicoEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentRussell Sage FoundationUniversity of MarylandNational Alliance for Research on Schizophrenia and DepressionZonMwSouth African Medical Research CouncilH2020 European Research CouncilSage FoundationUniversity of OxfordUniversiteit LeidenEuropean CommissionFundação de Amparo à Pesquisa do Estado de São PauloNederlandse Organisatie voor Wetenschappelijk OnderzoekHarvard UniversityBiogenNational Institute of Child Health and Human DevelopmentSanofiNational Science FoundationCarnegie Corporation of New YorkFoundation for the National Institutes of HealthUniversity of Southern CaliforniaMinisterie van Volksgezondheid, Welzijn en Sport
KeywordsTemperamentAnxietyPsychologyMega-Developmental psychologyNeuroscienceClinical psychologyPsychoanalysisPersonalityPsychiatry

Abstract

fetched live from OpenAlex

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: = .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. PLAIN LANGUAGE SUMMARY: 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. 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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Meta-analysis · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.004
Threshold uncertainty score0.014

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.002
Bibliometrics0.0020.001
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0010.001
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0040.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.009
GPT teacher head0.290
Teacher spread0.280 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designMeta-analysis
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

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Citations0
Published2025
Admission routes2
Has abstractyes

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Same venueJournal of the American Academy of Child & Adolescent Psychiatry→Same topicChild and Adolescent Psychosocial and Emotional Development→French-language works237,207→