Aggression subtypes relate to distinct resting state functional connectivity in children and adolescents with disruptive behavior

Julia E Werhahn, Susanna Mohl, David Willinger, Lukasz Smigielski, Alexander Roth, Christoph Hofstetter, Philipp Stämpfli, Jilly Naaijen, Leandra M Mulder, Jeffrey C Glennon, Pieter J Hoekstra, Andrea Dietrich, Renee Kleine Deters, Pascal M Aggensteiner, Nathalie E Holz, Sarah Baumeister, Tobias Banaschewski, Melanie C Saam, Ulrike M E Schulze, David J LythgoeArjun Sethi, Michael C Craig, Mathilde Mastroianni, Ilyas Sagar-Ouriaghli, Paramala J Santosh, Mireia Rosa, Nuria Bargallo, Josefina Castro-Fornieles, Celso Arango, Maria J Penzol, Marcel P Zwiers, Barbara Franke, Jan K Buitelaar, Susanne Walitza, Daniel Brandeis

Research output: Journal article (peer-reviewed)Journal article

19 Citations (Scopus)


There is increasing evidence for altered brain resting state functional connectivity in adolescents with disruptive behavior. While a considerable body of behavioral research points to differences between reactive and proactive aggression, it remains unknown whether these two subtypes have dissociable effects on connectivity. Additionally, callous-unemotional traits are important specifiers in subtyping aggressive behavior along the affective dimension. Accordingly, we examined associations between two aggression subtypes along with callous-unemotional traits using a seed-to-voxel approach. Six functionally relevant seeds were selected to probe the salience and the default mode network, based on their presumed role in aggression. The resting state sequence was acquired from 207 children and adolescents of both sexes [mean age (standard deviation) = 13.30 (2.60); range = 8.02-18.35] as part of a Europe-based multi-center study. One hundred eighteen individuals exhibiting disruptive behavior (conduct disorder/oppositional defiant disorder) with varying comorbid attention-deficit/hyperactivity disorder (ADHD) symptoms were studied, together with 89 healthy controls. Proactive aggression was associated with increased left amygdala-precuneus coupling, while reactive aggression related to hyper-connectivities of the posterior cingulate cortex (PCC) to the parahippocampus, the left amygdala to the precuneus and to hypo-connectivity between the right anterior insula and the nucleus caudate. Callous-unemotional traits were linked to distinct hyper-connectivities to frontal, parietal, and cingulate areas. Additionally, compared to controls, cases demonstrated reduced connectivity of the PCC and left anterior insula to left frontal areas, the latter only when controlling for ADHD scores. Taken together, this study revealed aggression-subtype-specific patterns involving areas associated with emotion, empathy, morality, and cognitive control.

Original languageEnglish
Pages (from-to)1237-1249
Number of pages13
JournalEuropean Child and Adolescent Psychiatry
Issue number8
Publication statusPublished - Aug 2021
Externally publishedYes


  • Adolescent
  • Aggression
  • Amygdala
  • Attention Deficit and Disruptive Behavior Disorders
  • Child
  • Conduct Disorder/diagnostic imaging
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Problem Behavior


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