Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
Department of Psychiatry, University of California San Diego, La Jolla, CA 92093, USA.
Int J Mol Sci. 2022 Mar 15;23(6):3176. doi: 10.3390/ijms23063176.
Externalizing behavior in its more extreme form is often considered a problem to the individual, their families, teachers, and society as a whole. Several brain structures have been linked to externalizing behavior and such associations may arise if the (co)development of externalizing behavior and brain structures share the same genetic and/or environmental factor(s). We assessed externalizing behavior with the Child Behavior Checklist and Youth Self Report, and the brain volumes and white matter integrity (fractional anisotropy [FA] and mean diffusivity [MD]) with magnetic resonance imaging in the BrainSCALE cohort, which consisted of twins and their older siblings from 112 families measured longitudinally at ages 10, 13, and 18 years for the twins. Genetic covariance modeling based on the classical twin design, extended to also include siblings of twins, showed that genes influence externalizing behavior and changes therein ( up to 88%). More pronounced externalizing behavior was associated with higher FA (observed correlation up to +0.20) and lower MD ( up to -0.20), with sizeable genetic correlations (FA up to +0.42; MD up to -0.33). The cortical gray matter (CGM; up to -0.20) and cerebral white matter (CWM; up to +0.20) volume were phenotypically but not genetically associated with externalizing behavior. These results suggest a potential mediating role for global brain structures in the display of externalizing behavior during adolescence that are both partially explained by the influence of the same genetic factor.
外化行为在其更极端的形式中，通常被认为是个体、他们的家庭、教师和整个社会的问题。一些大脑结构与外化行为有关，如果外化行为和大脑结构的（共同）发展共享相同的遗传和/或环境因素，那么这种关联就会出现。我们使用儿童行为检查表和青少年自我报告评估了外化行为，使用磁共振成像评估了大脑 SCALE 队列中的大脑体积和白质完整性（各向异性分数 [FA] 和平均扩散系数 [MD]），该队列由双胞胎及其年长的兄弟姐妹组成，112 个家庭中的双胞胎在 10、13 和 18 岁时进行了纵向测量。基于经典的双胞胎设计的遗传协方差建模，扩展到也包括双胞胎的兄弟姐妹，结果表明基因影响外化行为及其变化（高达 88%）。更明显的外化行为与更高的 FA（观察到的相关性高达+0.20）和更低的 MD（高达-0.20）相关，具有相当大的遗传相关性（FA 高达+0.42；MD 高达-0.33）。皮质灰质（CGM；高达-0.20）和大脑白质（CWM；高达+0.20）体积与外化行为具有表型关联但无遗传关联。这些结果表明，全球大脑结构在青春期外化行为的表现中可能具有潜在的中介作用，而这种作用部分是由相同遗传因素的影响所解释的。
