Bas-Hoogendam Janna Marie, Bernstein Rachel A, Benson Brenda E, Frank Samuel E C, Buss Kristin A, Gunther Kelley E, Pérez-Edgar Koraly, Salum Giovanni A, Jackowski Andrea, Bressan Rodrigo A, Zugman André, Degnan Kathryn A, Filippi Courtney A, Fox Nathan, Henderson Heather A, Tang Alva, Zeytinoglu Selin, Harrewijn Anita, Hillegers Manon H J, Muetzel Ryan L, White Tonya, van IJzendoorn Marinus H, Emden Schwartz Carl Robert, Felicione Julia, DeYoung Kathryn A, Shackman Alexander J, Smith Jason F, Tillman Rachael, van den Berg Yvonne H M, Cillessen Antonius H N, Roelofs Karin, Tyborowska Anna, Hill Shirley Y, Battaglia Marco, Tettamanti Marco, Dougherty Lea R, Jin Jingwen, Klein Daniel N, Leung Hoi-Chung, Avery Suzanne N, Blackford Jennifer Urbano, Clauss Jacqueline A, Bjork James M, Hettema John M, Moore Ashlee A, Roberson-Nay Roxann, Sawyers Chelsea, Hayden Elizabeth P, Liu Pan, Vandermeer Matthew R J, Goldsmit H Hill, Planalp Elizabeth M, Nichols Thomas E, Thompson Paul M, Westenberg P Michiel, van der Wee Nic J A, Groenewold Nynke A, Stein Dan J, Winkler Anderson M, Pine Daniel S
Leiden 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.
National Institute of Mental Health, Bethesda, Maryland.
J Am Acad Child Adolesc Psychiatry. 2025 Jul 4. doi: 10.1016/j.jaac.2025.06.026.
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 (p = .037) and thickness of the right superior parietal region (p = .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.
Structural Brain Correlates of Childhood Inhibited Temperament: An ENIGMA-Anxiety Mega-analysis. https://www.jaacap.org/article/S0890-8567(22)00299-4/fulltext.
儿童抑制性气质（cIT）与内化性精神病理学发展风险增加相关。通过结构磁共振成像（MRI）确定的神经生物学特征可能阐明cIT的神经基础，但相关研究较少，且往往集中于特定感兴趣区域。此外，目前的研究结果缺乏重复性。来自ENIGMA-焦虑症工作组的这项预先注册分析采用全面的全脑方法，研究了与cIT相关的脑结构特征。
汇总来自国际研究地点（欧洲、北美、南美）的气质评估（行为观察、家长/教师报告或13岁前关于cIT的自我报告）和MRI数据（扫描时年龄，6 - 25岁）进行荟萃分析。经过图像处理和质量控制后，在3803名参与者中研究了cIT与脑结构之间的关联。考虑了皮质下体积、皮质厚度和表面积（主要分析）以及详细的皮质下特征（如亚核、亚区、部分容积效应；探索性分析）。
在整个样本中，cIT与脑结构之间无论是作为主效应还是与性别或年龄的相互作用均无关联。亚组分析（基于cIT评估类型）显示，在有家长/教师报告cIT水平的青少年中，cIT与性别在平均皮质厚度（p = 0.037）和右上顶叶区域厚度（p = 0.029）上存在相互作用。探索性分析在海马体、壳核和尾状核中发现了一些结果，但大多数在多重检验的统计校正后未通过。
尽管顶叶区域的作用值得进一步研究，但这项荟萃分析未发现cIT与区域脑结构之间存在一致的关联。未来的研究应考虑cIT中的脑功能，最好采用纵向设计。
儿童抑制性气质的脑结构相关性：一项ENIGMA-焦虑症荟萃分析。https://www.jaacap.org/article/S0890-8567(22)00299-4/fulltext 。
