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, André Zugman, Kathryn A Degnan, Courtney A Filippi, Nathan Fox, Heather A Henderson, Alva Tang, Selin Zeytinoglu, Anita Harrewijn, Manon H J Hillegers, Ryan L Muetzel, Tonya White, Marinus H van IJzendoorn, Carl Robert Emden Schwartz, Julia Felicione, Kathryn A DeYoung, Alexander J Shackman, Jason F Smith, Rachael 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
{"title":"Structural Brain Correlates of Childhood Inhibited Temperament: An ENIGMA-Anxiety Mega-Analysis.","authors":"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, André Zugman, Kathryn A Degnan, Courtney A Filippi, Nathan Fox, Heather A Henderson, Alva Tang, Selin Zeytinoglu, Anita Harrewijn, Manon H J Hillegers, Ryan L Muetzel, Tonya White, Marinus H van IJzendoorn, Carl Robert Emden Schwartz, Julia Felicione, Kathryn A DeYoung, Alexander J Shackman, Jason F Smith, Rachael 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","doi":"10.1016/j.jaac.2025.06.026","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>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 pre-registered analysis from the ENIGMA-Anxiety Working Group examined structural brain characteristics associated with cIT using a comprehensive whole-brain approach.</p><p><strong>Method: </strong>Temperament assessments (behavioral observations, parental/teacher reports or self-reports on cIT before age 13) 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 (e.g. subnuclei, subfields, partial volume effects; exploratory analyses) were considered.</p><p><strong>Results: </strong>In the full sample, cIT showed no relation with brain structure, neither as a main effect nor in interactions with sex or age. Subgroup analyses (based on cIT-assessment type) revealed cIT by sex interactions on mean cortical thickness (p<sub>MC-FWER</sub> = 0.037) and thickness of the right superior parietal region (p<sub>MC-FWER</sub> = 0.029) in youth with parental/teacher reports on cIT-levels. Exploratory analyses revealed findings in hippocampus, putamen and caudate, but most did not survive statistical correction for multiple testing.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":17186,"journal":{"name":"Journal of the American Academy of Child and Adolescent Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.2000,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of the American Academy of Child and Adolescent Psychiatry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.jaac.2025.06.026","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PEDIATRICS","Score":null,"Total":0}
引用次数: 0
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 pre-registered 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, parental/teacher reports or self-reports on cIT before age 13) 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 (e.g. subnuclei, subfields, partial volume effects; exploratory analyses) were considered.
Results: In the full sample, cIT showed no relation with brain structure, neither as a main effect nor in interactions with sex or age. Subgroup analyses (based on cIT-assessment type) revealed cIT by sex interactions on mean cortical thickness (pMC-FWER = 0.037) and thickness of the right superior parietal region (pMC-FWER = 0.029) in youth with parental/teacher reports on cIT-levels. Exploratory analyses revealed findings in 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.
期刊介绍：
The Journal of the American Academy of Child & Adolescent Psychiatry (JAACAP) is dedicated to advancing the field of child and adolescent psychiatry through the publication of original research and papers of theoretical, scientific, and clinical significance. Our primary focus is on the mental health of children, adolescents, and families.
We welcome unpublished manuscripts that explore various perspectives, ranging from genetic, epidemiological, neurobiological, and psychopathological research, to cognitive, behavioral, psychodynamic, and other psychotherapeutic investigations. We also encourage submissions that delve into parent-child, interpersonal, and family research, as well as clinical and empirical studies conducted in inpatient, outpatient, consultation-liaison, and school-based settings.
In addition to publishing research, we aim to promote the well-being of children and families by featuring scholarly papers on topics such as health policy, legislation, advocacy, culture, society, and service provision in relation to mental health.
At JAACAP, we strive to foster collaboration and dialogue among researchers, clinicians, and policy-makers in order to enhance our understanding and approach to child and adolescent mental health.
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