Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany.
Donders Center for Brain, Cognition and Behavior, Radboud University Nijmegen, Nijmegen, The Netherlands.
Psychol Med. 2023 Jul;53(9):4012-4021. doi: 10.1017/S003329172200068X. Epub 2022 Apr 22.
Disruptive behavior disorders (DBD) are heterogeneous at the clinical and the biological level. Therefore, the aims were to dissect the heterogeneous neurodevelopmental deviations of the affective brain circuitry and provide an integration of these differences across modalities.
We combined two novel approaches. First, normative modeling to map deviations from the typical age-related pattern at the level of the individual of (i) activity during emotion matching and (ii) of anatomical images derived from DBD cases ( = 77) and controls ( = 52) aged 8-18 years from the EU-funded Aggressotype and MATRICS consortia. Second, linked independent component analysis to integrate subject-specific deviations from both modalities.
While cases exhibited on average a higher activity than would be expected for their age during face processing in regions such as the amygdala when compared to controls these positive deviations were widespread at the individual level. A multimodal integration of all functional and anatomical deviations explained 23% of the variance in the clinical DBD phenotype. Most notably, the top marker, encompassing the default mode network (DMN) and subcortical regions such as the amygdala and the striatum, was related to aggression across the whole sample.
Overall increased age-related deviations in the amygdala in DBD suggest a maturational delay, which has to be further validated in future studies. Further, the integration of individual deviation patterns from multiple imaging modalities allowed to dissect some of the heterogeneity of DBD and identified the DMN, the striatum and the amygdala as neural signatures that were associated with aggression.
破坏性行为障碍(DBD)在临床和生物学层面上具有异质性。因此,本研究旨在剖析情感大脑回路的神经发育差异,并整合不同模态的这些差异。
我们结合了两种新方法。首先,进行规范建模,以映射个体在(i)情绪匹配期间的活动和(ii)来自欧盟资助的 Aggressotype 和 MATRICS 联盟的 DBD 病例(=77)和对照组(=52)8-18 岁的解剖图像中偏离典型年龄相关模式的情况。其次,采用链接独立成分分析整合两种模态的个体特异性偏差。
与对照组相比,病例在处理面部时,其杏仁核等区域的活动水平平均高于其年龄应有的水平,表现出正偏差。这些积极的偏差在个体水平上广泛存在。对所有功能和解剖学偏差进行的多模态整合,解释了临床 DBD 表型 23%的方差。值得注意的是,包含默认模式网络(DMN)和杏仁核、纹状体等皮质下区域的最高标志物,与整个样本的攻击性有关。
DBD 患者杏仁核的年龄相关性偏差增加,表明存在成熟延迟,这需要在未来的研究中进一步验证。此外,整合来自多个成像模态的个体偏差模式,可以剖析 DBD 的一些异质性,并确定 DMN、纹状体和杏仁核作为与攻击性相关的神经特征。