Aggression subtypes relate to distinct resting state functional connectivity in children and adolescents with disruptive
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ORIGINAL CONTRIBUTION
Aggression subtypes relate to distinct resting state functional connectivity in children and adolescents with disruptive behavior Julia E. Werhahn1,2 · Susanna Mohl1 · David Willinger1,2 · Lukasz Smigielski1 · Alexander Roth1,2 · Christoph Hofstetter1 · Philipp Stämpfli3 · Jilly Naaijen4,5 · Leandra M. Mulder4,5 · Jeffrey C. Glennon4 · Pieter J. Hoekstra6 · Andrea Dietrich6 · Renee Kleine Deters6 · Pascal M. Aggensteiner7 · Nathalie E. Holz7 · Sarah Baumeister7 · Tobias Banaschewski7 · Melanie C. Saam8 · Ulrike M. E. Schulze8 · David J. Lythgoe9 · Arjun Sethi10 · Michael C. Craig10 · Mathilde Mastroianni11 · Ilyas Sagar‑Ouriaghli11 · Paramala J. Santosh11 · Mireia Rosa12 · Nuria Bargallo13 · Josefina Castro‑Fornieles14 · Celso Arango15 · Maria J. Penzol15 · Marcel P. Zwiers5 · Barbara Franke16,17 · Jan K. Buitelaar4,18 · Susanne Walitza1,2 · Daniel Brandeis1,2,7 Received: 16 November 2019 / Accepted: 8 July 2020 © The Author(s) 2020
Abstract 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 aggressionsubtype-specific patterns involving areas associated with emotion, empathy, morality, and cognitive control. Keywords Reactive aggression · Proactive aggression · Callous-unemotional traits · Default mode network · Amygdala · Functio
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