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Aggression Subtypes Relate to Distinct Resting State Functional Connectivity in Disruptive Children and Adolescents

Julia E Werhahn, Susanna Mohl, David Willinger, Lukasz Smigielski, Alexander Roth, Christoph Hofstetter, Philipp Stämpfli, Isabelle Häberling, 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 Aragno, Maria J Penzol, Barbara Franke, Marcel P Zwiers, Jan K Buitelaar, Susanne Walitza, Daniel Brandeis
doi: https://doi.org/10.1101/462382
Julia E Werhahn
1Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Zurich, Switzerland
2Neuroscience Center Zurich, University and ETH Zurich, Zurich, Switzerland
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  • For correspondence: julia.werhahn@gmx.ch
Susanna Mohl
1Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Zurich, Switzerland
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David Willinger
1Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Zurich, Switzerland
2Neuroscience Center Zurich, University and ETH Zurich, Zurich, Switzerland
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Lukasz Smigielski
1Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Zurich, Switzerland
2Neuroscience Center Zurich, University and ETH Zurich, Zurich, Switzerland
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Alexander Roth
1Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Zurich, Switzerland
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Christoph Hofstetter
1Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Zurich, Switzerland
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Philipp Stämpfli
1Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Zurich, Switzerland
3MR-Center of the Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital of Psychiatry Zurich, University of Zurich, Zurich, Switzerland
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Isabelle Häberling
1Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Zurich, Switzerland
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Jilly Naaijen
4Radboud University Medical Center, Donders Institute for Brain, Cognition and Behavior, Department of Cognitive Neuroscience, Nijmegen, The Netherlands
5Radboud University, Donders Institute for Brain, Cognition and Behavior, Centre for Cognitive Neuroimaging, Nijmegen, The Netherlands
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Leandra M Mulder
4Radboud University Medical Center, Donders Institute for Brain, Cognition and Behavior, Department of Cognitive Neuroscience, Nijmegen, The Netherlands
5Radboud University, Donders Institute for Brain, Cognition and Behavior, Centre for Cognitive Neuroimaging, Nijmegen, The Netherlands
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Jeffrey C Glennon
4Radboud University Medical Center, Donders Institute for Brain, Cognition and Behavior, Department of Cognitive Neuroscience, Nijmegen, The Netherlands
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Pieter J Hoekstra
6University of Groningen, University Medical Center Groningen, Department of Child and Adolescent Psychiatry, Groningen, The Netherlands
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Andrea Dietrich
6University of Groningen, University Medical Center Groningen, Department of Child and Adolescent Psychiatry, Groningen, The Netherlands
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Renee Kleine Deters
6University of Groningen, University Medical Center Groningen, Department of Child and Adolescent Psychiatry, Groningen, The Netherlands
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Pascal M Aggensteiner
7Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany
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Nathalie E Holz
7Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany
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Sarah Baumeister
7Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany
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Tobias Banaschewski
7Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany
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Melanie C Saam
8Department of Child and Adolescent Psychiatry/Psychotherapy, University Hospital, University of Ulm, Germany
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Ulrike M E Schulze
8Department of Child and Adolescent Psychiatry/Psychotherapy, University Hospital, University of Ulm, Germany
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David J Lythgoe
9Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK
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Arjun Sethi
9Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK
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Michael Craig
9Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK
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Mathilde Mastroianni
10Department of Child Psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK
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Ilyas Sagar-Ouriaghli
10Department of Child Psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK
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Paramala J Santosh
10Department of Child Psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK
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Mireia Rosa
11Child and Adolescent Psychiatry Department, Hospital Clinic of Barcelona, IDIBAPS, Barcelona, Spain
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Nuria Bargallo
12Clinic Image Diagnostic Center (CDIC), Hospital Clinic of Barcelona; Magnetic Resonance Image Core Facility, IDIBAPS, Barcelona, Spain
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Josefina Castro-Fornieles
13Child and Adolescent Psychiatry and Psychology Department, Institute Clinic of Neurosciences, Hospital Clinic of Barcelona, CIBERSAM, IDIBAPS, Department of Medicine, University of Barcelona, Barcelona, Spain
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Celso Aragno
14Child and Adolescent Psychiatry Department, Hospital General Universitario Gregorio Marañón School of Medicine, Universidad Complutense, IiSGM, CIBERSAM, Madrid, Spain
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Maria J Penzol
14Child and Adolescent Psychiatry Department, Hospital General Universitario Gregorio Marañón School of Medicine, Universidad Complutense, IiSGM, CIBERSAM, Madrid, Spain
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Barbara Franke
15Radboud University Medical Center, Donders Institute for Brain, Cognition and Behavior, Department of Human Genetics, Nijmegen, The Netherlands
16Radboud University Medical Center, Donders Institute for Brain, Cognition and Behavior, Department of Psychiatry, Nijmegen, The Netherlands
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Marcel P Zwiers
5Radboud University, Donders Institute for Brain, Cognition and Behavior, Centre for Cognitive Neuroimaging, Nijmegen, The Netherlands
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Jan K Buitelaar
4Radboud University Medical Center, Donders Institute for Brain, Cognition and Behavior, Department of Cognitive Neuroscience, Nijmegen, The Netherlands
17Karakter Child and Adolescent Psychiatry University Center, Nijmegen, The Netherlands
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Susanne Walitza
1Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Zurich, Switzerland
2Neuroscience Center Zurich, University and ETH Zurich, Zurich, Switzerland
18Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland
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Daniel Brandeis
1Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Zurich, Switzerland
2Neuroscience Center Zurich, University and ETH Zurich, Zurich, Switzerland
7Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany
18Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland
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Abstract

Objective There is increasing evidence for altered resting state functional connectivity (rsFC) in adolescents with disruptive behavior. Despite considerable ongoing behavioral research suggesting also important differences relating to reactive and proactive aggression, the corresponding rsFC correlates have not been studied to date. We therefore examined associations between these aggression subtypes along with subdimensions of callous-unemotional (CU) traits and rsFC using predefined seeds in aggression-related salience network (SN) and default mode network (DMN).

Method Aggression subtype-specific whole-brain rsFC of SN and DMN seeds was investigated in a resting state sequence (mean acquisition time = 8 min 25 sec) acquired from 207 children and adolescents of both sexes aged 8 - 18 years (mean age (SD) = 13.30 (2.60) years; range = 8.02 – 18.35) in a multi-center study. One hundred eighteen individuals exhibited disruptive behavior (conduct disorder/oppositional defiant disorder) with different levels of comorbid ADHD symptoms, 89 were healthy.

Results Compared to healthy controls, cases demonstrated reduced DMN and – after controlling for ADHD scores – SN seed-based rsFC with left hemispheric frontal clusters. We found increased and distinct aggression-subtype specific rsFC patterns. Specifically, reactive and proactive aggression correlated with distinct SN and DMN seed-based rsFC patterns. CU dimensions led to different DMN and SN rsFC with clusters including frontal, parietal, and cingulate areas.

Conclusions This first study investigating reactive and proactive aggression along with CU dimensions reveals new subtype-specific whole-brain rsFC patterns in brain regions linked to processes like emotion, empathy, moral, and cognitive control.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Aggression Subtypes Relate to Distinct Resting State Functional Connectivity in Disruptive Children and Adolescents
Julia E Werhahn, Susanna Mohl, David Willinger, Lukasz Smigielski, Alexander Roth, Christoph Hofstetter, Philipp Stämpfli, Isabelle Häberling, 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 Aragno, Maria J Penzol, Barbara Franke, Marcel P Zwiers, Jan K Buitelaar, Susanne Walitza, Daniel Brandeis
bioRxiv 462382; doi: https://doi.org/10.1101/462382
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Aggression Subtypes Relate to Distinct Resting State Functional Connectivity in Disruptive Children and Adolescents
Julia E Werhahn, Susanna Mohl, David Willinger, Lukasz Smigielski, Alexander Roth, Christoph Hofstetter, Philipp Stämpfli, Isabelle Häberling, 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 Aragno, Maria J Penzol, Barbara Franke, Marcel P Zwiers, Jan K Buitelaar, Susanne Walitza, Daniel Brandeis
bioRxiv 462382; doi: https://doi.org/10.1101/462382

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