Age-related brain deviations and aggression

Nathalie E. Holz, Dorothea L. Floris, Alberto Llera, Pascal M. Aggensteiner, Seyed Mostafa Kia, Thomas Wolfers, Sarah Baumeister, Boris Böttinger, Jeffrey C. Glennon, Pieter J. Hoekstra, Andrea Dietrich, Melanie C. Saam, Ulrike M.E. Schulze, David J. Lythgoe, Steve C.R. Williams, Paramala Santosh, Mireia Rosa-Justicia, Nuria Bargallo, Josefina Castro-Fornieles, Celso ArangoMaria J. Penzol, Susanne Walitza, Andreas Meyer-Lindenberg, Marcel Zwiers, Barbara Franke, Jan Buitelaar, Jilly Naaijen, Daniel Brandeis, Christian Beckmann, Tobias Banaschewski, Andre F. Marquand

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)


Background 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. Methods 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 (n = 77) and controls (n = 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. Results 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. Conclusions 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.

Original languageEnglish
JournalPsychological Medicine
Early online date22 Apr 2022
Publication statusE-pub ahead of print - 22 Apr 2022


  • Aggression
  • disruptive behavior disorders
  • emotion processing
  • fMRI
  • normative modeling


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