Evidence map›Paper›PMID 40619094›Full record

ArticleJournal of the American Academy of Child and Adolescent Psychiatry2026

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

Janna Marie Bas-Hoogendam, Rachel A Bernstein, Brenda E Benson, Samuel E C Frank, Kristin A Buss, Kelley E Gunther, Koraly Pérez-Edgar, Giovanni A Salum, Andrea Jackowski, Rodrigo A Bressan and 50 more

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Article in Journal of the American Academy of Child and Adolescent Psychiatry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

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0 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

60 authors.

Janna Marie Bas-HoogendamLeiden University, Leiden, the Netherlands; Leiden University Medical Center, Leiden, the Netherlands; Leiden Institute for Brain and Cognition, Leiden, the Netherlands; National Institute of Mental Health, Bethesda, Maryland. Electronic address: j.m.hoogendam@fsw.leidenuniv.nl.
Rachel A BernsteinNational Institute of Mental Health, Bethesda, Maryland.
Brenda E BensonNational Institute of Mental Health, Bethesda, Maryland.
Samuel E C FrankNational Institute of Mental Health, Bethesda, Maryland.
Kristin A BussThe Pennsylvania State University, University Park, Pennsylvania.
Kelley E GuntherThe Pennsylvania State University, University Park, Pennsylvania; University of Maryland, College Park, Maryland.
Koraly Pérez-EdgarThe Pennsylvania State University, University Park, Pennsylvania.
Giovanni A SalumHospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; National Institute of Developmental Psychiatry, São Paulo, Brazil; Child Mind Institute, New York, New York.
Andrea JackowskiFederal University of São Paulo, São Paulo, Brazil.
Rodrigo A BressanFederal University of São Paulo, São Paulo, Brazil.
André ZugmanNational Institute of Mental Health, Bethesda, Maryland.
Kathryn A DegnanThe Catholic University of America, Washington, DC.
Courtney A FilippiNew York University Grossman School of Medicine, New York, New York.
Nathan A FoxUniversity of Maryland, College Park, Maryland.
Heather A HendersonUniversity of Waterloo, Waterloo, Ontario, Canada.
Alva TangUniversity of Texas at Dellas, Richardson, Texas.
Selin ZeytinogluUniversity of Maryland, College Park, Maryland; Tulane University, New Orleans, Louisiana.
Anita HarrewijnErasmus University Rotterdam, Rotterdam, the Netherlands.
Manon H J HillegersErasmus University Medical Center, Rotterdam, the Netherlands.
Ryan L MuetzelErasmus University Medical Center, Rotterdam, the Netherlands.
Tonya WhiteNational Institute of Mental Health, Bethesda, Maryland; Erasmus University Medical Center, Rotterdam, the Netherlands.
Marinus H van IJzendoornUCL, London, United Kingdom; Universidad San Sebastián, Santiago de Chile, Chile.
Carl E SchwartzMassachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
Julia M FelicioneMassachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Tufts University, Medford, Massachusetts.
Kathryn A DeYoungUniversity of Maryland, College Park, Maryland.
Alexander J ShackmanUniversity of Maryland, College Park, Maryland.
Jason F SmithUniversity of Maryland, College Park, Maryland.
Rachael M TillmanUniversity of Maryland, College Park, Maryland.
Yvonne H M van den BergRadboud University, Behavioural Science Institute, Nijmegen, the Netherlands.
Antonius H N CillessenRadboud University, Behavioural Science Institute, Nijmegen, the Netherlands.
Karin RoelofsRadboud University, Behavioural Science Institute, Nijmegen, the Netherlands.
Anna TyborowskaRadboud University, Behavioural Science Institute, Nijmegen, the Netherlands.
Shirley Y HillUniversity of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Marco BattagliaUniversity of Toronto, Toronto, Ontario, Canada; Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
Marco TettamantiUniversity of Milan-Bicocca, Milan, Italy.
Lea R DoughertyUniversity of Maryland, College Park, Maryland.
Jingwen JinThe University of Hong Kong, Hong Kong.
Daniel N KleinStony Brook University, Stony Brook, New York.
Hoi-Chung LeungStony Brook University, Stony Brook, New York.
Suzanne N AveryVanderbilt University Medical Center, Nashville, Tennessee.
Jennifer Urbano BlackfordVanderbilt University Medical Center, Nashville, Tennessee; Munroe-Meyer Institute, University of Nebraska Medical Center, Omaha, Nebraska.
Jacqueline A ClaussMassachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; University of Maryland Medical School, Baltimore, Maryland.
James M BjorkVirginia Commonwealth University, Richmond, Virginia.
John M HettemaTexas A&M University, Bryan, Texas.
Ashlee A MooreState University of New York, Oswego, New York.
Roxann Roberson-NayUniversity of Virginia, Charlottesville, Virginia.
Chelsea SawyersVirginia Commonwealth University, Richmond, Virginia.
Elizabeth P HaydenWestern University, London, Ontario, Canada.
Pan LiuWestern University, London, Ontario, Canada; University of Alberta, Edmonton, Alberta, Canada.
Matthew R J VandermeerWestern University, London, Ontario, Canada.
H Hill GoldsmithUniversity of Wisconsin-Madison, Madison, Wisconsin.
Elizabeth M PlanalpUniversity of Wisconsin-Madison, Madison, Wisconsin.
Thomas E NicholsUniversity of Oxford, Oxford, United Kingdom.
Paul M ThompsonUniversity of Southern California, Marina del Rey, California.
P Michiel WestenbergLeiden University, Leiden, the Netherlands; Leiden Institute for Brain and Cognition, Leiden, the Netherlands.
Nic J A van der WeeLeiden University Medical Center, Leiden, the Netherlands; Leiden Institute for Brain and Cognition, Leiden, the Netherlands.
Nynke A GroenewoldUniversity of Cape Town, Cape Town, South Africa.
Dan J SteinUniversity of Cape Town, Cape Town, South Africa.
Anderson M WinklerNational Institute of Mental Health, Bethesda, Maryland; The University of Texas Rio Grande Valley, Brownsville, Texas.
Daniel S PineNational Institute of Mental Health, Bethesda, Maryland.

Funding

Fmri Studies Of Risk For Mood And Anxiety Disorders In ChildrenZIAMH002782 · NIMH · NATIONAL INSTITUTE OF MENTAL HEALTH · PI PINE, DANIEL · 2009 to 2025
$28.3M
WISCONSIN CENTER ON MENTAL RETARDATION: CORE SUPPORTP30HD003352 · NICHD · UNIVERSITY OF WISCONSIN-MADISON · PI MAILICK, MARSHA RUTH · 1985 to 2015
$25.2M
Temperamental Low PE in Preschoolers and Depression RiskR01MH069942 · NIMH · STATE UNIVERSITY NEW YORK STONY BROOK · PI KLEIN, DANIEL N · 2004 to 2023
$14.2M
Stress, Lead, Iron Deficiency and NeurodevelopmentR01ES013744 · NIEHS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Robert O Wright · 2007 to 2026
$13.4M
Examining Brain Development, Context, and Culture as Mediators and Moderators of the Relation between Adverse Childhood Experiences (ACEs) and Substance (Ab)useU01DA051037 · NIDA · VIRGINIA COMMONWEALTH UNIVERSITY · PI James M Bjork, MICHAEL CHURTON NEALE · 2020 to 2026
$11.0M
Training U54EB020403 · NIBIB · UNIVERSITY OF SOUTHERN CALIFORNIA · PI THOMPSON, PAUL M · 2014 to 2018
$10.1M
Large-scale meta-analysis of functional MRI dataR01MH096906 · NIMH · UNIVERSITY OF TEXAS AT AUSTIN · PI Alejandro De La Vega · 2012 to 2026
$7.9M
13/24 The Healthy Brain and Child Development National ConsortiumU01DA055361 · NIDA · PENNSYLVANIA STATE UNIVERSITY, THE · PI Koraly E Perez-Edgar, Aleksandra Ewa Zgierska · 2021 to 2026
$7.8M
BIOLOGICAL RISK FACTORS IN RELATIVES OF ALCOHOLIC WOMENR01AA008082 · NIAAA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI HILL, SHIRLEY · 1990 to 2014
$7.6M
Research Training: Psychiatric &Statistical GeneticsT32MH020030 · NIMH · VIRGINIA COMMONWEALTH UNIVERSITY · PI HERMINE H MAES, MICHAEL CHURTON NEALE · 1999 to 2026
$6.7M
Trajectories of Behavioral Inibition and Risk for AnxietyU01MH093349 · NIMH · UNIV OF MARYLAND, COLLEGE PARK · PI FOX, NATHAN A · 2011 to 2020
$6.6M
Research within the Section on Social and Cognitive Developmental Neuroscience ZIAMH002986 · NIMH · NATIONAL INSTITUTE OF MENTAL HEALTH · PI WHITE, TONYA · 2023 to 2025
$6.3M
Intramural NIH HHS ZIA MH002782Intramural NIH HHS ZIA MH002986NIAAA NIH HHS R01 AA005909NIAAA NIH HHS R01 AA008082NIAAA NIH HHS R01 AA018289NIAAA NIH HHS R01 AA021746NIAAA NIH HHS R01 AA030042NIAAA NIH HHS R01 AA031261NIBIB NIH HHS U54 EB020403NICHD NIH HHS P30 HD003352NICHD NIH HHS U54 HD090256NIDA NIH HHS U01 DA051037NIDA NIH HHS U01 DA055361NIEHS NIH HHS R01 ES013744NIEHS NIH HHS R01 ES033436NIMH NIH HHS F30 MH097344NIMH NIH HHS F31 MH111229NIMH NIH HHS F32 MH127869NIMH NIH HHS K01 MH083052NIMH NIH HHS K01 MH113710NIMH NIH HHS R00 MH125878NIMH NIH HHS R01 MH059785NIMH NIH HHS R01 MH069942NIMH NIH HHS R01 MH071467NIMH NIH HHS R01 MH094633NIMH NIH HHS R01 MH096906NIMH NIH HHS R01 MH098055NIMH NIH HHS R01 MH101504NIMH NIH HHS R01 MH101518NIMH NIH HHS R01 MH107444NIMH NIH HHS R01 MH109692NIMH NIH HHS R01 MH116147NIMH NIH HHS R01 MH121246NIMH NIH HHS R01 MH121385NIMH NIH HHS R01 MH121409NIMH NIH HHS R01 MH122487NIMH NIH HHS R01 MH130007NIMH NIH HHS R01 MH131264NIMH NIH HHS R01 MH133652NIMH NIH HHS R21 MH106924NIMH NIH HHS R56 MH126349NIMH NIH HHS RF1 MH123163NIMH NIH HHS T32 MH020030NIMH NIH HHS U01 MH093349
6 · The paper itself

Abstract

objectiveChildhood 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.

methodTemperament 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.

resultsIn 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 (p

conclusionThis 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.

Indexed as

AnxietyBrainInhibition, PsychologicalTemperamentAdolescentAdultChildFemaleHumansMagnetic Resonance ImagingMaleYoung Adultadolescenceanxiety disorderschildhoodmagnetic resonance imaging (MRI)temperament

Identifiers

PMID40619094
PMCPMC12321241

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