Shared and Distinct Brain Alterations in Youth with Internalising or Externalising Disorders
Presented During:
Tuesday, June 25, 2024: 12:00 PM - 1:15 PM
COEX
Room:
Hall D 2
Poster No:
498
Submission Type:
Abstract Submission
Authors:
Sophie Townend1, Marlene Staginnus1, Yidian Gao2, Barbara Franke3,4,5, Martine Hoogman3,4,5, Lianne Schmaal6,7, Dick Veltman8, Elena Pozzi6,7, Janna Marie Bas-Hoogendam9,10,11, Nynke Groenewold12,13, Dan Stein12,14, Nic van der Wee10,11, Moji Aghajani15,8, Charlotte Cecil16,17, Eduard Klapwijk18,19, Arielle Baskin-Sommers20, Daniel Pine21, Sophia Thomopoulos22, Neda Jahanshad22, Paul Thompson22, Esther Walton1, Stephane De Brito2, Graeme Fairchild1, ENIGMA consortium23
Institutions:
1Department of Psychology, University of Bath, Bath, United Kingdom, 2Centre for Human Brain Health and Institute for Mental Health, University of Birmingham, Birmingham, United Kingdom, 3Department of Cognitive Neuroscience, Radboud University Medical Center, Nijmegen, Netherlands, 4Department of Psychiatry, Radboud University Medical Center, Nijmegen, Netherlands, 5Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, Netherlands, 6Orygen, Parkville, Australia, 7Centre for Youth Mental Health, The University of Melbourne, Parkville, Australia, 8Department of Psychiatry, Amsterdam University Medical Centers, Vrije Universiteit Medical Center, Amsterdam, Netherlands, 9Institute of Psychology, Leiden University, Leiden, Netherlands, 10Department of Psychiatry, Leiden University Medical Center, Leiden, Netherlands, 11Leiden Institute for Brain and Cognition, Leiden, Netherlands, 12Department of Psychiatry and Mental Health, Neuroscience Institute, University of Cape Town, Cape Town, South Africa, 13South African Medical Research Council (SA-MRC) Unit on Child and Adolescent Health, Department of Paediatrics and Child Health, Red Cross War Memorial Children’s Hospital, University of Cape Town, Cape Town, South Africa, 14South African Medical Research Council Unit on Risk & Resilience in Mental Disorders, University of Cape Town, Cape Town, South Africa, 15Leiden University, Institute of Education & Child Studies, Section Forensic Family & Youth Care, Leiden, Netherlands, 16Department of Child and Adolescent Psychiatry/Psychology, Erasmus Medical Centre, Rotterdam, Netherlands, 17Department of Epidemiology, Erasmus Medical Centre, Rotterdam, Netherlands, 18Erasmus School of Social and Behavioural Sciences, Erasmus University Rotterdam, Rotterdam, Netherlands, 19Brain and Development Research Center, Leiden University, Leiden, Netherlands, 20Department of Psychology, Yale University, New Haven, CT, 21National Institute of Mental Health (NIMH), National Institutes of Health (NIH), Bethesda, MD, 22Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, USC, Marina del Rey, CA, 23Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Marina del Rey, CA, CA
First Author:
Co-Author(s):
Yidian Gao
Centre for Human Brain Health and Institute for Mental Health, University of Birmingham
Birmingham, United Kingdom
Centre for Human Brain Health and Institute for Mental Health, University of Birmingham
Birmingham, United Kingdom
Barbara Franke
Department of Cognitive Neuroscience, Radboud University Medical Center|Department of Psychiatry, Radboud University Medical Center|Donders Institute for Brain, Cognition and Behaviour, Radboud University
Nijmegen, Netherlands|Nijmegen, Netherlands|Nijmegen, Netherlands
Department of Cognitive Neuroscience, Radboud University Medical Center|Department of Psychiatry, Radboud University Medical Center|Donders Institute for Brain, Cognition and Behaviour, Radboud University
Nijmegen, Netherlands|Nijmegen, Netherlands|Nijmegen, Netherlands
Martine Hoogman
Department of Cognitive Neuroscience, Radboud University Medical Center|Department of Psychiatry, Radboud University Medical Center|Donders Institute for Brain, Cognition and Behaviour, Radboud University
Nijmegen, Netherlands|Nijmegen, Netherlands|Nijmegen, Netherlands
Department of Cognitive Neuroscience, Radboud University Medical Center|Department of Psychiatry, Radboud University Medical Center|Donders Institute for Brain, Cognition and Behaviour, Radboud University
Nijmegen, Netherlands|Nijmegen, Netherlands|Nijmegen, Netherlands
Lianne Schmaal
Orygen|Centre for Youth Mental Health, The University of Melbourne
Parkville, Australia|Parkville, Australia
Orygen|Centre for Youth Mental Health, The University of Melbourne
Parkville, Australia|Parkville, Australia
Dick Veltman
Department of Psychiatry, Amsterdam University Medical Centers, Vrije Universiteit Medical Center
Amsterdam, Netherlands
Department of Psychiatry, Amsterdam University Medical Centers, Vrije Universiteit Medical Center
Amsterdam, Netherlands
Elena Pozzi
Orygen|Centre for Youth Mental Health, The University of Melbourne
Parkville, Australia|Parkville, Australia
Orygen|Centre for Youth Mental Health, The University of Melbourne
Parkville, Australia|Parkville, Australia
Janna Marie Bas-Hoogendam
Institute of Psychology, Leiden University|Department of Psychiatry, Leiden University Medical Center|Leiden Institute for Brain and Cognition
Leiden, Netherlands|Leiden, Netherlands|Leiden, Netherlands
Institute of Psychology, Leiden University|Department of Psychiatry, Leiden University Medical Center|Leiden Institute for Brain and Cognition
Leiden, Netherlands|Leiden, Netherlands|Leiden, Netherlands
Nynke Groenewold
Department of Psychiatry and Mental Health, Neuroscience Institute, University of Cape Town|South African Medical Research Council (SA-MRC) Unit on Child and Adolescent Health, Department of Paediatrics and Child Health, Red Cross War Memorial Children’s Hospital, University of Cape Town
Cape Town, South Africa|Cape Town, South Africa
Department of Psychiatry and Mental Health, Neuroscience Institute, University of Cape Town|South African Medical Research Council (SA-MRC) Unit on Child and Adolescent Health, Department of Paediatrics and Child Health, Red Cross War Memorial Children’s Hospital, University of Cape Town
Cape Town, South Africa|Cape Town, South Africa
Dan Stein
Department of Psychiatry and Mental Health, Neuroscience Institute, University of Cape Town|South African Medical Research Council Unit on Risk & Resilience in Mental Disorders, University of Cape Town
Cape Town, South Africa|Cape Town, South Africa
Department of Psychiatry and Mental Health, Neuroscience Institute, University of Cape Town|South African Medical Research Council Unit on Risk & Resilience in Mental Disorders, University of Cape Town
Cape Town, South Africa|Cape Town, South Africa
Nic van der Wee
Department of Psychiatry, Leiden University Medical Center|Leiden Institute for Brain and Cognition
Leiden, Netherlands|Leiden, Netherlands
Department of Psychiatry, Leiden University Medical Center|Leiden Institute for Brain and Cognition
Leiden, Netherlands|Leiden, Netherlands
Moji Aghajani
Leiden University, Institute of Education & Child Studies, Section Forensic Family & Youth Care|Department of Psychiatry, Amsterdam University Medical Centers, Vrije Universiteit Medical Center
Leiden, Netherlands|Amsterdam, Netherlands
Leiden University, Institute of Education & Child Studies, Section Forensic Family & Youth Care|Department of Psychiatry, Amsterdam University Medical Centers, Vrije Universiteit Medical Center
Leiden, Netherlands|Amsterdam, Netherlands
Charlotte Cecil
Department of Child and Adolescent Psychiatry/Psychology, Erasmus Medical Centre|Department of Epidemiology, Erasmus Medical Centre
Rotterdam, Netherlands|Rotterdam, Netherlands
Department of Child and Adolescent Psychiatry/Psychology, Erasmus Medical Centre|Department of Epidemiology, Erasmus Medical Centre
Rotterdam, Netherlands|Rotterdam, Netherlands
Eduard Klapwijk
Erasmus School of Social and Behavioural Sciences, Erasmus University Rotterdam|Brain and Development Research Center, Leiden University
Rotterdam, Netherlands|Leiden, Netherlands
Erasmus School of Social and Behavioural Sciences, Erasmus University Rotterdam|Brain and Development Research Center, Leiden University
Rotterdam, Netherlands|Leiden, Netherlands
Daniel Pine
National Institute of Mental Health (NIMH), National Institutes of Health (NIH)
Bethesda, MD
National Institute of Mental Health (NIMH), National Institutes of Health (NIH)
Bethesda, MD
Sophia Thomopoulos
Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, USC
Marina del Rey, CA
Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, USC
Marina del Rey, CA
Neda Jahanshad
Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, USC
Marina del Rey, CA
Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, USC
Marina del Rey, CA
Paul Thompson
Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, USC
Marina del Rey, CA
Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, USC
Marina del Rey, CA
Stephane De Brito
Centre for Human Brain Health and Institute for Mental Health, University of Birmingham
Birmingham, United Kingdom
Centre for Human Brain Health and Institute for Mental Health, University of Birmingham
Birmingham, United Kingdom
ENIGMA consortium
Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute
Marina del Rey, CA, CA
Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute
Marina del Rey, CA, CA
Introduction:
Externalising and internalising disorders are common in youth but are often studied in isolation, preventing an investigation of the transdiagnostic vulnerability which may underlie them. Recent studies have attempted to identify unique versus shared neurobiological alterations across these disorders (e.g., Durham et al., 2021; Gold et al., 2016; Goodkind et al., 2015; Yu et al., 2023), but results have been inconsistent, likely due to heterogeneous sample selection and methods. Using data from the ENIGMA consortium, we conducted a mega-analysis to identify shared and distinct cortical and subcortical alterations between internalising (anxiety disorders and depression) and externalising (attention-deficit/hyperactivity disorder [ADHD] and conduct disorder [CD]) disorders in youth.
Methods:
Structural T1-weighted MRI data from healthy controls (n=4,743) and patients with anxiety disorders (n=1,044), depression (n=504), ADHD (n=1,317) and CD (n=1,172) aged 4-21 years were collated from 67 international samples. Using ENIGMA protocols, we assessed group differences in regional cortical thickness and surface area (34 regions, averaged across hemispheres), and subcortical volume (7 regions, averaged across hemispheres) using general linear models. We adjusted for age, sex, and intracranial volume [ICV] (where appropriate). False-discovery rate correction was applied for each outcome measure, and site effects were adjusted for using ComBat (Radua et al., 2020). Sensitivity analyses explored the impact of IQ and medication status.
Results:
We observed transdiagnostic effects, with all four disorders characterised by lower surface area in the insula, entorhinal cortex, and middle temporal gyrus, and lower amygdala volume (Cohen's ds=0.07-0.24). All disorders were also associated with global reductions in total surface area and ICV (ds=0.11-0.25). Externalising-specific (i.e., CD and ADHD) reductions in surface area were observed in several fronto-parietal regions (ds=0.08-0.13), but no internalising-specific (i.e., anxiety disorders and depression) effects were identified. Disorder-specific alterations were identified for ADHD, CD, and anxiety disorders, but not for depression. Overall, six out of 34 regions showed case-control differences in cortical thickness, but there were more widespread effects for surface area and subcortical volume. Of the disorder-specific effects observed for surface area and subcortical volume, most were specific to CD. Most group differences in surface area and cortical thickness survived adjustment for IQ, but were more affected by medication status adjustment, while the opposite was true for subcortical volumes.
·Results_Figure1
Conclusions:
In the first mega-analysis to investigate structural brain alterations in internalising and externalising disorders in youth, both disorder-specific and shared effects were found, including transdiagnostic effects on surface area and subcortical volume. These findings may guide future research into the neural mechanisms of transdiagnostic vulnerability, as well as understanding how specific disorders map onto distinct brain networks.
Disorders of the Nervous System:
Neurodevelopmental/ Early Life (eg. ADHD, autism)
Psychiatric (eg. Depression, Anxiety, Schizophrenia) 1
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Cortical Anatomy and Brain Mapping
Subcortical Structures
Novel Imaging Acquisition Methods:
Anatomical MRI 2
Keywords:
Meta- Analysis
Pediatric Disorders
Psychiatric Disorders
STRUCTURAL MRI
Other - Transdiagnostic
1|2Indicates the priority used for review
Provide references using author date format
Durham, E. L., Jeong, H. J., Moore, T. M., Dupont, R. M., Cardenas-Iniguez, C., Cui, Z., ... & Kaczkurkin, A. N. (2021). Association of gray matter volumes with general and specific dimensions of psychopathology in children. Neuropsychopharmacology, 46(7), 1333-1339.
Gold, A. L., Brotman, M. A., Adleman, N. E., Lever, S. N., Steuber, E. R., Fromm, S. J., ... & Leibenluft, E. (2016). Comparing brain morphometry across multiple childhood psychiatric disorders. Journal of the American Academy of Child & Adolescent Psychiatry, 55(12), 1027-1037.
Goodkind, M., Eickhoff, S. B., Oathes, D. J., Jiang, Y., Chang, A., Jones-Hagata, L. B., ... & Etkin, A. (2015). Identification of a common neurobiological substrate for mental illness. JAMA Psychiatry, 72(4), 305-315.
Radua, J., Vieta, E., Shinohara, R., Kochunov, P., Quidé, Y., Green, M. J., ... & Pineda-Zapata, J. (2020). Increased power by harmonizing structural MRI site differences with the ComBat batch adjustment method in ENIGMA. NeuroImage, 218, 116956.
Yu, G., Liu, Z., Wu, X., Becker, B., Zhang, K., Fan, H., ... & Zhang, J. (2023). Common and disorder-specific cortical thickness alterations in internalizing, externalizing and thought disorders during early adolescence: an Adolescent Brain and Cognitive Development study. Journal of Psychiatry and Neuroscience, 48(5), E345-E356.