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This project has received funding from the European Union's Seventh Framework Programme for research, technological development, and demonstration under grant agreement 602805 (Aggressotype) and no 603016 (MATRICS). This manuscript reflects only the author's view and the European Union is not liable for any use that may be made of the information contained herein. B. Franke received additional funding from a personal Vici grant of the Dutch Organisation for Scientific Research (grant 016-130-669) and from a grant for the Dutch National Science Agenda for the NWA NeurolabNL project (grant 400 17 602). S. Walitza received royalties from Thieme, Hogrefe, Kohlhammer, Springer, Beltz. Her work was supported in the last 5 years by the Swiss National Science Foundation (SNF), diff. EU FP7s, HSM Hochspezialisierte Medizin of the Kanton Zurich, Switzerland, Bfarm Germany, ZInEP, Hartmann Muller Stiftung, Olga Mayenfisch, Gertrud Thalmann Fonds. Outside professional activities and interests are declared under the link of the University of Zurich www.uzh.ch/prof/ssl-dir.T.Banaschewski served in an advisory or consultancy role for Actelion, Hexal Pharma, Lilly, Medice, Novartis, Oxford outcomes, Otsuka, PCM Scientific, Shire, and Viforpharma. He received conference support or speaker's fee by Medice, Novartis, and Shire. He is/has been involved in clinical trials conducted by Shire and Viforpharma. He received royalties from Hogrefe, Kohlhammer, CIP Medien, and Oxford University Press. JK Buitelaar has been a consultant to/member of the advisory board of and/or speaker for Janssen Cilag BV, Eli Lilly, Bristol-Myer Squibb, Shering Plough, UCB, Shire, Novartis, and Servier. He is not an employee of any of these companies, nor a stock shareholder of any of these companies. D. Brandeis serves as an unpaid scientific consultant for an EU-funded neurofeedback trial. C. Arango has been a consultant to or has received honoraria or grants from Acadia, Ambrosseti, Caja Navarra, CIBERSAM, Fundacion Alicia Koplowitz, Forum, Instituto de Salud Carlos III, Gedeon Richter, Janssen Cilag, Lundbeck, Merck, Ministerio de Ciencia e Innovacion, Ministerio de Sanidad, Ministerio de Economia y Competitividad, Mutua Madrilena, Otsuka, Roche, Servier, Shire, Schering Plough, Sumitomo Dainippon Pharma, Sunovio, and Takeda. All other authors report no potential conflict of interest. The present work is unrelated to the above grants and relationships. The authors express their deepest gratitude to all participating children and adolescents and their families.

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The effects of callous-unemotional traits and aggression subtypes on amygdala activity in response to negative faces

Publicated to:Psychological Medicine. 52 (3): 476-484 - 2022-02-01 52(3), DOI: 10.1017/s0033291720002111

Authors: Aggensteiner, PM; Holz, NE; Böttinger, BW; Baumeister, S; Hohmann, S; Banaschewski, T; Brandeis, D; Werhahn, JE; Walitza, S; Naaijen, J; Ilbegi, S; Glennon, JC; Buitelaar, JK; Zwiers, MP; Hoekstra, PJ; Dietrich, A; Deters, RK; Saam, MC; Schulze, UME; Lythgoe, DJ; Sethi, A; Craig, MC; Mastroianni, M; Sagar-Ouriaghli, I; Santosh, PJ; Rosa, M; Bargallo, N; Castro-Fornieles, J; Arango, C; Penzol, MJ; Vidal, J; Franke, B

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Abstract

Brain imaging studies have shown altered amygdala activity during emotion processing in children and adolescents with oppositional defiant disorder (ODD) and conduct disorder (CD) compared to typically developing children and adolescents (TD). Here we aimed to assess whether aggression-related subtypes (reactive and proactive aggression) and callous-unemotional (CU) traits predicted variation in amygdala activity and skin conductance (SC) response during emotion processing.We included 177 participants (n = 108 cases with disruptive behaviour and/or ODD/CD and n = 69 TD), aged 8-18 years, across nine sites in Europe, as part of the EU Aggressotype and MATRICS projects. All participants performed an emotional face-matching functional magnetic resonance imaging task.Differences between cases and TD in affective processing, as well as specificity of activation patterns for aggression subtypes and CU traits, were assessed. Simultaneous SC recordings were acquired in a subsample (n = 63). Cases compared to TDs showed higher amygdala activity in response to negative faces (fearful and angry) v. shapes. Subtyping cases according to aggression-related subtypes did not significantly influence on amygdala activity; while stratification based on CU traits was more sensitive and revealed decreased amygdala activity in the high CU group. SC responses were significantly lower in cases and negatively correlated with CU traits, reactive and proactive aggression.Our results showed differences in amygdala activity and SC responses to emotional faces between cases with ODD/CD and TD, while CU traits moderate both central (amygdala) and peripheral (SC) responses. Our insights regarding subtypes and trait-specific aggression could be used for improved diagnostics and personalized treatment.

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