Different whole-brain functional connectivity correlates of reactive-proactive aggression and callous-unemotional traits in children and adolescents with disruptive behaviors

Julia E Werhahn; Lukasz Smigielski; Seda Sacu; Susanna Mohl; David Willinger; 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 Lythgoe; Arjun Sethi; Michael 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

doi:10.1016/j.nicl.2023.103542

Different whole-brain functional connectivity correlates of reactive-proactive aggression and callous-unemotional traits in children and adolescents with disruptive behaviors

Neuroimage Clin. 2023:40:103542. doi: 10.1016/j.nicl.2023.103542. Epub 2023 Nov 13.

Authors

Julia E Werhahn¹, Lukasz Smigielski¹, Seda Sacu², Susanna Mohl¹, David Willinger¹, Jilly Naaijen³, Leandra M Mulder³, Jeffrey C Glennon⁴, Pieter J Hoekstra⁵, Andrea Dietrich⁵, Renee Kleine Deters⁵, Pascal M Aggensteiner², Nathalie E Holz², Sarah Baumeister², Tobias Banaschewski², Melanie C Saam⁶, Ulrike M E Schulze⁶, David J Lythgoe⁷, Arjun Sethi⁸, Michael Craig⁸, Mathilde Mastroianni⁹, Ilyas Sagar-Ouriaghli⁹, Paramala J Santosh⁹, Mireia Rosa¹⁰, Nuria Bargallo¹¹, Josefina Castro-Fornieles¹², Celso Arango¹³, Maria J Penzol¹³, Marcel P Zwiers¹⁴, Barbara Franke¹⁵, Jan K Buitelaar¹⁶, Susanne Walitza¹⁷, Daniel Brandeis¹⁸

Affiliations

¹ Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Zurich, Switzerland.
² Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
³ Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Radboud University, Nijmegen, The Netherlands; Centre for Cognitive Neuroimaging, Donders Institute for Brain, Cognition and Behavior, Radboud University, Nijmegen, The Netherlands.
⁴ Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Radboud University, Nijmegen, The Netherlands; Conway Institute of Biomedical and Biomolecular Research, School of Medicine, University College Dublin, Dublin, Ireland.
⁵ Department of Child and Adolescent Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
⁶ Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital, University of Ulm, Ulm, Germany.
⁷ Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
⁸ Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
⁹ Department of Child Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
¹⁰ Child and Adolescent Psychiatry Department, Hospital Clinic of Barcelona, IDIBAPS, Barcelona, Spain.
¹¹ Clinic Image Diagnostic Center (CDIC), Hospital Clinic of Barcelona, Magnetic Resonance Image Core Facility, IDIBAPS, Barcelona, Spain.
¹² Child and Adolescent Psychiatry and Psychology Department, Institute Clinic of Neurosciences, Hospital Clinic of Barcelona, CIBERSAM, IDIBAPS, Department of Medicine, University of Barcelona, Barcelona, Spain.
¹³ Child and Adolescent Psychiatry Department, Hospital General Universitario Gregorio Marañón School of Medicine, Universidad Complutense, IiSGM, CIBERSAM, Madrid, Spain.
¹⁴ Centre for Cognitive Neuroimaging, Donders Institute for Brain, Cognition and Behavior, Radboud University, Nijmegen, The Netherlands.
¹⁵ Departments of Human Genetics and Psychiatry, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center. Radboud University, Nijmegen, The Netherlands.
¹⁶ Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Radboud University, Nijmegen, The Netherlands; Karakter Child and Adolescent Psychiatry University Center, Radboud University Medical Center, Radboud University, Nijmegen, The Netherlands.
¹⁷ Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Zurich, Switzerland; Neuroscience Center Zurich, University of Zurich and ETH Zurich, Zurich, Switzerland.
¹⁸ Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Zurich, Switzerland; Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; Neuroscience Center Zurich, University of Zurich and ETH Zurich, Zurich, Switzerland. Electronic address: brandeis@kjpd.uzh.ch.

Abstract

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.

Keywords: Adolescents; Callous-unemotional traits; Children; Proactive aggression; Reactive aggression; Resting-state fMRI.

Publication types

Multicenter Study

MeSH terms

Adolescent
Aggression / psychology
Brain / diagnostic imaging
Child
Conduct Disorder* / diagnostic imaging
Emotions
Humans
Male
Problem Behavior*