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

Bas-Hoogendam JM., Bernstein RA., Benson BE., Frank SEC., Buss KA., Gunther KE., Pérez-Edgar K., Salum GA., Jackowski A., Bressan RA., Zugman A., Degnan KA., Filippi CA., Fox NA., Henderson HA., Tang A., Zeytinoglu S., Harrewijn A., Hillegers MHJ., Muetzel RL., White T., van IJzendoorn MH., Schwartz CE., Felicione JM., DeYoung KA., Shackman AJ., Smith JF., Tillman RM., van den Berg YHM., Cillessen AHN., Roelofs K., Tyborowska A., Hill SY., Battaglia M., Tettamanti M., Dougherty LR., Jin J., Klein DN., Leung H-C., Avery SN., Blackford JU., Clauss JA., Bjork JM., Hettema JM., Moore AA., Roberson-Nay R., Sawyers C., Hayden EP., Liu P., Vandermeer MRJ., Goldsmith HH., Planalp EM., Nichols TE., Thompson PM., Westenberg PM., van der Wee NJA., Groenewold NA., Stein DJ., Winkler AM., Pine DS.

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 (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.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.Study registration informationStructural Brain Correlates of Childhood Inhibited Temperament: An ENIGMA-Anxiety Mega-analysis. https://www.jaacap.org/article/S0890-8567(22)00299-4/fulltext.

More information Original publication

DOI

10.1016/j.jaac.2025.06.026

Type

Journal article

Publication Date

2025-07-01T00:00:00+00:00

Addresses

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