TY - JOUR
T1 - Different whole-brain functional connectivity correlates of reactive-proactive aggression and callous-unemotional traits in children and adolescents with disruptive behaviors
AU - Werhahn, Julia E.
AU - Smigielski, Lukasz
AU - Sacu, Seda
AU - Mohl, Susanna
AU - Willinger, David
AU - Naaijen, Jilly
AU - Mulder, Leandra M.
AU - Glennon, Jeffrey C.
AU - Hoekstra, Pieter J.
AU - Dietrich, Andrea
AU - Deters, Renee Kleine
AU - Aggensteiner, Pascal M.
AU - Holz, Nathalie E.
AU - Baumeister, Sarah
AU - Banaschewski, Tobias
AU - Saam, Melanie C.
AU - Schulze, Ulrike M.E.
AU - Lythgoe, David J.
AU - Sethi, Arjun
AU - Craig, Michael
AU - Mastroianni, Mathilde
AU - Sagar-Ouriaghli, Ilyas
AU - Santosh, Paramala J.
AU - Rosa, Mireia
AU - Bargallo, Nuria
AU - Castro-Fornieles, Josefina
AU - Arango, Celso
AU - Penzol, Maria J.
AU - Zwiers, Marcel P.
AU - Franke, Barbara
AU - Buitelaar, Jan K.
AU - Walitza, Susanne
AU - Brandeis, Daniel
N1 - Funding Information:
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 authors’ views, and the European Union is not liable for any use that may be made of the information contained herein.
TB has served in an advisory or consultancy role for Actelion, Hexal Pharma, Lilly, Lundbeck, Medice, Neurim Pharmaceuticals, Novartis, and Shire; he received conference support or speaker’s fees from Lilly, Medice, Novartis, and Shire. He has also been involved in clinical trials conducted by Shire and Viforpharma and has received royalties from Hogrefe, Kohlhammer, CIP Medien, and Oxford University Press. CA has been a consultant to or has received honoraria or grants from Acadia, Ambrosseti, Gedeon Richter, Janssen Cilag, Lundbeck, Merck, Otsuka, Roche, Servier, Shire, Schering Plough, Sumitomo Dainippon Pharma, Sunovion, and Takeda. DB served as an unpaid scientific advisor for an EU-funded neurofeedback trial unrelated to the present work. BF receives funding from a personal Vici grant from the Dutch Organisation for Scientific Research (Grant 016 130 669) and the Dutch National Science Agenda for the NWANeurolabNL project (Grant 400 17 602). She received educational speaking fees from Shire and Medicine. S.W. has received in the last 5 years royalties from Thieme, Hogrefe, Kohlhammer, Springer, and Beltz. In 2023, she received speakers honorary from Takeda and Medice. Her work was supported in the last years by the Swiss National Science Foundation (SNF), diff. EU FP7s, HSM Hochspezialisierte Medizin of the Kanton Zurich, Switzerland, Bfarm Germany, ZInEP, Hartmann Müller Stiftung, Olga Mayenfisch, Gertrud Thalmann, Vontobel, Unicentia, Erika Schwarz, Heuberg Fonds, National Government of Health (BAG), Gesundheitsförderung Schweiz, and Horizon Europe. Outside professional activities and interests are declared on the web page of the University of Zurich (https://www.uzh.ch/prof/ssl-dir/interessenbindungen/client/web/).
Publisher Copyright:
© 2023 The Authors
PY - 2023
Y1 - 2023
N2 - Background: Disruptive behavior in children and adolescents can manifest as reactive aggression and proactive aggression and is modulated by callous-unemotional traits and other comorbidities. Neural correlates of these aggression dimensions or subtypes and comorbid symptoms remain largely unknown. This multi-center study investigated the relationship between resting state functional connectivity (rsFC) and aggression subtypes considering comorbidities. Methods: The large sample of children and adolescents aged 8–18 years (n = 207; mean age = 13.30±2.60 years, 150 males) included 118 cases with disruptive behavior (80 with Oppositional Defiant Disorder and/or Conduct Disorder) and 89 controls. Attention-deficit/hyperactivity disorder (ADHD) and anxiety symptom scores were analyzed as covariates when assessing group differences and dimensional aggression effects on hypothesis-free global and local voxel-to-voxel whole-brain rsFC based on functional magnetic resonance imaging at 3 Tesla. Results: Compared to controls, the cases demonstrated altered rsFC in frontal areas, when anxiety but not ADHD symptoms were controlled for. For cases, reactive and proactive aggression scores were related to global and local rsFC in the central gyrus and precuneus, regions linked to aggression-related impairments. Callous-unemotional trait severity was correlated with ICC in the inferior and middle temporal regions implicated in empathy, emotion, and reward processing. Most observed aggression subtype-specific patterns could only be identified when ADHD and anxiety were controlled for. Conclusions: This study clarifies that hypothesis-free brain connectivity measures can disentangle distinct though overlapping dimensions of aggression in youths. Moreover, our results highlight the importance of considering comorbid symptoms to detect aggression-related rsFC alterations in youths.
AB - Background: Disruptive behavior in children and adolescents can manifest as reactive aggression and proactive aggression and is modulated by callous-unemotional traits and other comorbidities. Neural correlates of these aggression dimensions or subtypes and comorbid symptoms remain largely unknown. This multi-center study investigated the relationship between resting state functional connectivity (rsFC) and aggression subtypes considering comorbidities. Methods: The large sample of children and adolescents aged 8–18 years (n = 207; mean age = 13.30±2.60 years, 150 males) included 118 cases with disruptive behavior (80 with Oppositional Defiant Disorder and/or Conduct Disorder) and 89 controls. Attention-deficit/hyperactivity disorder (ADHD) and anxiety symptom scores were analyzed as covariates when assessing group differences and dimensional aggression effects on hypothesis-free global and local voxel-to-voxel whole-brain rsFC based on functional magnetic resonance imaging at 3 Tesla. Results: Compared to controls, the cases demonstrated altered rsFC in frontal areas, when anxiety but not ADHD symptoms were controlled for. For cases, reactive and proactive aggression scores were related to global and local rsFC in the central gyrus and precuneus, regions linked to aggression-related impairments. Callous-unemotional trait severity was correlated with ICC in the inferior and middle temporal regions implicated in empathy, emotion, and reward processing. Most observed aggression subtype-specific patterns could only be identified when ADHD and anxiety were controlled for. Conclusions: This study clarifies that hypothesis-free brain connectivity measures can disentangle distinct though overlapping dimensions of aggression in youths. Moreover, our results highlight the importance of considering comorbid symptoms to detect aggression-related rsFC alterations in youths.
KW - Adolescents
KW - Callous-unemotional traits
KW - Children
KW - Proactive aggression
KW - Reactive aggression
KW - Resting-state fMRI
UR - http://www.scopus.com/inward/record.url?scp=85177853016&partnerID=8YFLogxK
U2 - 10.1016/j.nicl.2023.103542
DO - 10.1016/j.nicl.2023.103542
M3 - Article
C2 - 37988996
AN - SCOPUS:85177853016
SN - 2213-1582
VL - 40
JO - NeuroImage: Clinical
JF - NeuroImage: Clinical
M1 - 103542
ER -