Dimensional Relationships Between Conduct Problems and Brain Structure: An ENIGMA Mega-Analysis
Poster No:
375
Submission Type:
Abstract Submission
Authors:
Marlene Staginnus1, Yidian Gao2, Sophie Townend1, Moji Aghajani3,4, Eduard Klapwijk5,6, Charlotte Cecil7,8, Arielle Baskin-Sommers9, Daniel Pine10, Sophia Thomopoulos11, Neda Jahanshad11, Paul Thompson11, Esther Walton1, Stephane De Brito2, Graeme Fairchild1, ENIGMA Antisocial Behavior Working Group12
Institutions:
1Department of Psychology, University of Bath, Bath, United Kingdom, 2Centre for Human Brain Health, School of Psychology, University of Birmingham, Birmingham, United Kingdom, 3Institute of Education & Child Studies, Section Forensic Family & Youth Care, Leiden University, Leiden, The Netherlands, 4Department of Psychiatry, Amsterdam University Medical Centers, VU University, Amsterdam, The Netherlands, 5Erasmus School of Social and Behavioural Sciences, Erasmus University Rotterdam, Rotterdam, The Netherlands, 6Brain and Development Research Center, Leiden University, Leiden, The Netherlands, 7Department of Child and Adolescent Psychiatry/Psychology, Erasmus Medical Centre, Rotterdam, The Netherlands, 8Department of Epidemiology, Erasmus Medical Centre, Rotterdam, The Netherlands, 9Department of Psychology, Yale University, New Haven, CT, United States, 10National Institute of Mental Health (NIMH), National Institutes of Health (NIH), Bethesda, MD, United States, 11Keck School of Medicine, University of Southern California, Marina del Rey, CA, United States, 12Universities of Birmingham and Bath, Birmingham/Bath, United Kingdom
First Author:
Co-Author(s):
Yidian Gao
Centre for Human Brain Health, School of Psychology, University of Birmingham
Birmingham, United Kingdom
Centre for Human Brain Health, School of Psychology, University of Birmingham
Birmingham, United Kingdom
Moji Aghajani
Institute of Education & Child Studies, Section Forensic Family & Youth Care, Leiden University|Department of Psychiatry, Amsterdam University Medical Centers, VU University
Leiden, The Netherlands|Amsterdam, The Netherlands
Institute of Education & Child Studies, Section Forensic Family & Youth Care, Leiden University|Department of Psychiatry, Amsterdam University Medical Centers, VU University
Leiden, The Netherlands|Amsterdam, The Netherlands
Eduard Klapwijk
Erasmus School of Social and Behavioural Sciences, Erasmus University Rotterdam|Brain and Development Research Center, Leiden University
Rotterdam, The Netherlands|Leiden, The Netherlands
Erasmus School of Social and Behavioural Sciences, Erasmus University Rotterdam|Brain and Development Research Center, Leiden University
Rotterdam, The Netherlands|Leiden, The Netherlands
Charlotte Cecil
Department of Child and Adolescent Psychiatry/Psychology, Erasmus Medical Centre|Department of Epidemiology, Erasmus Medical Centre
Rotterdam, The Netherlands|Rotterdam, The Netherlands
Department of Child and Adolescent Psychiatry/Psychology, Erasmus Medical Centre|Department of Epidemiology, Erasmus Medical Centre
Rotterdam, The Netherlands|Rotterdam, The Netherlands
Daniel Pine
National Institute of Mental Health (NIMH), National Institutes of Health (NIH)
Bethesda, MD, United States
National Institute of Mental Health (NIMH), National Institutes of Health (NIH)
Bethesda, MD, United States
Sophia Thomopoulos
Keck School of Medicine, University of Southern California
Marina del Rey, CA, United States
Keck School of Medicine, University of Southern California
Marina del Rey, CA, United States
Neda Jahanshad
Keck School of Medicine, University of Southern California
Marina del Rey, CA, United States
Keck School of Medicine, University of Southern California
Marina del Rey, CA, United States
Paul Thompson
Keck School of Medicine, University of Southern California
Marina del Rey, CA, United States
Keck School of Medicine, University of Southern California
Marina del Rey, CA, United States
Stephane De Brito
Centre for Human Brain Health, School of Psychology, University of Birmingham
Birmingham, United Kingdom
Centre for Human Brain Health, School of Psychology, University of Birmingham
Birmingham, United Kingdom
ENIGMA Antisocial Behavior Working Group
Universities of Birmingham and Bath
Birmingham/Bath, United Kingdom
Universities of Birmingham and Bath
Birmingham/Bath, United Kingdom
Introduction:
Conduct disorder (CD) and elevated conduct problems (CP) are associated with various negative outcomes (e.g., poor mental and physical health, delinquency) and are a substantial economic burden (Erskine et al., 2014). The first case-control analysis focusing on CD by the ENIGMA-Antisocial Behavior working group provided robust evidence of brain structural alterations in this population. Relative to controls, youth with CD showed lower surface area across most of the cortex (Gao, Staginnus et al., in preparation). However, evidence that CP occur on a continuum highlights the importance of complementary studies that investigate CP as a dimensional construct, including in non-clinical samples. Therefore, leveraging the largest-ever multi-site neuroimaging database on youth CP compiled by the ENIGMA-Antisocial Behavior working group, we aimed to evaluate associations between CP and cortical thickness, surface area, and subcortical volumes.
Methods:
This pre-registered mega-analysis (doi.org/10.17605/OSF.IO/NZJ3R) combines T1-weighted MRI data of children and adolescents from 18 international case-control and community-/population-based cohorts. Data were pre-processed with FreeSurfer and quality controlled according to the standardized ENIGMA protocols. CP were assessed using the Child Behavior Checklist or the Strengths and Difficulties Questionnaire, which were transformed into a common metric using the percentage of maximum possible score method (Cohen, 1999). We used linear models to examine associations of CP with measures of regional cortical thickness, surface area (34 regions, averaged across hemispheres, respectively), and subcortical volumes (7 regions, averaged across hemispheres), controlling for age, sex, and intracranial volume. We adjusted for site effects using the modified ComBat functions (Radua et al., 2020) and applied a False Discovery Rate correction per brain metric.
Results:
Preliminary analyses including 13 of the 18 cohorts and 10,576 youths (aged 7-19 years, MAge=10.35 years, 46% girls) revealed significant negative associations between CP and cortical thickness (average thickness and 7 of the 34 regions investigated), surface area (total surface area and 27 of 34 regions), subcortical volumes (3 of 7 regions, including the amygdala), and intracranial volume (all pFDR < .05). Just one positive association between CP and caudal anterior cingulate thickness was observed (pFDR = .017). Effect sizes expressed as standardized beta estimates ranged between 0.02 and 0.10 (see Figure 1 for more details).
Conclusions:
Preliminary findings indicate subtle yet widespread associations between youth CP and brain structure, especially for surface area, which largely overlap with alterations observed in the first case-control ENIGMA study of CD (Gao, Staginnus et al., in preparation; 15% participant overlap). Replicating these associations dimensionally provides robust evidence for quantitative associations between CP and brain structure across clinical and non-clinical samples. They further corroborate results from other ENIGMA disease working groups indicating that surface area is more affected than thickness in youth psychopathology (e.g., Hoogman et al., 2019; Schmaal et al., 2017). We will present findings obtained using the full sample including 18 cohorts, separate analyses of case-control and community-based samples, and interaction analyses testing whether associations between CP and brain structure differ based on age, sex, level of callous-unemotional traits, or presence of conduct disorder.
Disorders of the Nervous System:
Neurodevelopmental/ Early Life (eg. ADHD, autism) 1
Psychiatric (eg. Depression, Anxiety, Schizophrenia)
Lifespan Development:
Early life, Adolescence, Aging
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Cortical Anatomy and Brain Mapping
Novel Imaging Acquisition Methods:
Anatomical MRI 2
Keywords:
Meta- Analysis
Psychiatric Disorders
STRUCTURAL MRI
Other - Conduct Disorder; Conduct Problems; Antisocial Behavior; ENIGMA; FreeSurfer; Surface-Based Morphometry; Mega-Analysis
1|2Indicates the priority used for review
Provide references using author date format
Erskine, H.E., Ferrari, A.J., Polanczyk, G.V., Moffitt, T.E., Murray, C.J., Vos, T., ... & Scott, J. G. (2014), ‘The global burden of conduct disorder and attention‐deficit/hyperactivity disorder in 2010.’ Journal of Child Psychology and Psychiatry, vol. 55, no. 4, pp. 328-336.
Gao, Y., Staginnus, M., Aghajani, M, Klapwijk, E., Cecil, C., Baskin-Sommers, A., … De Brito, S.A. (in preparation), ‘A mega-analysis of cortical structure and subcortical volumes in conduct disorder in youth: Effects of sex, age-of-onset and callous-unemotional traits’
Hoogman, M., Muetzel, R., Guimaraes, J. P., Shumskaya, E., Mennes, M., Zwiers, M. P., ... Franke, B. (2019), ‘Brain imaging of the cortex in ADHD: a coordinated analysis of large-scale clinical and population-based samples’, American Journal of Psychiatry, vol. 176, no. 7, pp. 531-542.
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Schmaal, L., Hibar, D. P., Sämann, P. G., Hall, G. B., Baune, B. T., Jahanshad, N., ... Veltman, D. J. (2017), ‘Cortical abnormalities in adults and adolescents with major depression based on brain scans from 20 cohorts worldwide in the ENIGMA Major Depressive Disorder Working Group’, Molecular Psychiatry, vol. 22, no. 6, pp. 900-909.