Subcortical surface morphometry in substance dependence: An ENIGMA addiction working group study

Yann Chye¹, Scott Mackey², Boris A Gutman³, Christopher R K Ching⁴, Albert Batalla^{5

6}, Sara Blaine⁷, Samantha Brooks^{8

9}, Elisabeth C Caparelli¹⁰, Janna Cousijn¹¹, Alain Dagher¹², John J Foxe¹³, Anna E Goudriaan^{14

15}, Robert Hester¹⁶, Kent Hutchison¹⁷, Neda Jahanshad⁴, Anne M Kaag¹¹, Ozlem Korucuoglu¹⁸, Chiang-Shan R Li⁷, Edythe D London¹⁹, Valentina Lorenzetti^{1

20}, Maartje Luijten²¹, Rocio Martin-Santos⁶, Shashwath A Meda²², Reza Momenan²³, Angelica Morales¹⁹, Catherine Orr², Martin P Paulus^{24

25}, Godfrey Pearlson⁷, Liesbeth Reneman²⁶, Lianne Schmaal^{27

28}, Rajita Sinha⁷, Nadia Solowij^{29

30}, Dan J Stein³¹, Elliot A Stein¹⁰, Deborah Tang¹², Anne Uhlmann³², Ruth van Holst³³, Dick J Veltman³⁴, Antonio Verdejo-Garcia¹, Reinout W Wiers³⁵, Murat Yücel¹, Paul M Thompson⁴, Patricia Conrod³⁶, Hugh Garavan²

Affiliations

¹ Turner Institute for Brain and Mental Health, School of Psychological Sciences, Monash University, Clayton, Victoria, Australia.
² Departments of Psychiatry, University of Vermont, Burlington, VT, USA.
³ Biomedical Engineering, Illinois Institute of Technology, Chicago, IL, USA.
⁴ Department of Neurology, Keck School of Medicine, Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, University of Southern California, Los Angeles, CA, USA.
⁵ Department of Psychiatry, University Medical Centre Utrecht Brain Center, Utrecht University, Utrecht, The Netherlands.
⁶ Department of Psychiatry and Psychology, Hospital Clinic, IDIBAPS, CIBERSAM, Institute of Neuroscience, University of Barcelona, Barcelona, Spain.
⁷ Departments of Psychiatry and Neuroscience, Yale University School of Medicine, CT, USA.
⁸ Faculty of Health, School of Psychology, Liverpool John Moores University, L3 3AF, Liverpool UK.
⁹ Department of Neuroscience, Section of Functional Pharmacology, Uppsala University, 75240, Sweden.
¹⁰ Neuroimaging Research Branch, Intramural Research Program, National Institute of Drug Abuse, Baltimore, MD, USA.
¹¹ Department of Developmental Psychology, University of Amsterdam, The Netherlands.
¹² McConnell Brain Imaging Center, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
¹³ Department of Neuroscience & The Ernest J. Del Monte Institute for Neuroscience, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
¹⁴ Amsterdam UMC, Department of Psychiatry, Amsterdam Institute for Addiction Research, University of Amsterdam, Amsterdam, The Netherlands.
¹⁵ Department of Research and Quality of Care, Arkin Mental Health Care, Amsterdam, The Netherlands.
¹⁶ Melbourne School of Psychological Sciences, University of Melbourne, Melbourne, Victoria, Australia.
¹⁷ Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO, USA.
¹⁸ Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO, USA.
¹⁹ Jane and Terry Semel Institute of Neuroscience and Human Behavior, David Geffen School of Medicine, Universityof California at Los Angeles, Los Angeles, CA, USA.
²⁰ School of Psychology, Faculty of Health Sciences, Australian Catholic University, Melbourne, Victoria, Australia.
²¹ Behavioural Science Institute, Radboud University, Nijmegen, The Netherlands.
²² Olin Neuropsychiatry Research Center, Hartford Hospital/IOL, Hartford, CT, USA.
²³ Clinical NeuroImaging Research Core, Division of Intramural Clinical and BiologicalResearch, National Institute of Alcohol Abuse and Alcoholism, Bethesda, MD, USA.
²⁴ VA San Diego Healthcare System and Department of Psychiatry, University of California San Diego, CA, USA.
²⁵ Laureate Institute for Brain Research, Tulsa, OK, USA.
²⁶ Department of Radiology and Nuclear Medicine, Amsterdam UMC, location AMC, Amsterdam, The Netherlands.
²⁷ Orygen, The National Centre of Excellence in Youth Mental Health, Parkville, Australia.
²⁸ Centre for Youth Mental Health, The University of Melbourne, Parkville, Australia.
²⁹ School of Psychology and Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, New South Wales, Australia.
³⁰ The Australian Centre for Cannabinoid Clinical and Research Excellence (ACRE), New Lambton Heights, New South Wales, Australia.
³¹ SA MRC Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
³² Department of Psychiatry and Mental Health, Faculty of Health Sciences University of Cape Town, South Africa.
³³ Department of Psychiatry, University of Amsterdam, Amsterdam, The Netherlands.
³⁴ Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands.
³⁵ Addiction Development and Psychopathology (ADAPT) Lab, University of Amsterdam, Amsterdam, The Netherlands.
³⁶ Department of Psychiatry, Université de Montreal, CHU Ste Justine Hospital, Canada.

PMID: 31746534
PMCID: PMC7237314
DOI: 10.1111/adb.12830

Subcortical surface morphometry in substance dependence: An ENIGMA addiction working group study

Yann Chye et al. Addict Biol. 2020 Nov.

. 2020 Nov;25(6):e12830.

doi: 10.1111/adb.12830. Epub 2019 Nov 20.

Authors

Affiliations

¹ Turner Institute for Brain and Mental Health, School of Psychological Sciences, Monash University, Clayton, Victoria, Australia.
² Departments of Psychiatry, University of Vermont, Burlington, VT, USA.
³ Biomedical Engineering, Illinois Institute of Technology, Chicago, IL, USA.
⁴ Department of Neurology, Keck School of Medicine, Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, University of Southern California, Los Angeles, CA, USA.
⁵ Department of Psychiatry, University Medical Centre Utrecht Brain Center, Utrecht University, Utrecht, The Netherlands.
⁶ Department of Psychiatry and Psychology, Hospital Clinic, IDIBAPS, CIBERSAM, Institute of Neuroscience, University of Barcelona, Barcelona, Spain.
⁷ Departments of Psychiatry and Neuroscience, Yale University School of Medicine, CT, USA.
⁸ Faculty of Health, School of Psychology, Liverpool John Moores University, L3 3AF, Liverpool UK.
⁹ Department of Neuroscience, Section of Functional Pharmacology, Uppsala University, 75240, Sweden.
¹⁰ Neuroimaging Research Branch, Intramural Research Program, National Institute of Drug Abuse, Baltimore, MD, USA.
¹¹ Department of Developmental Psychology, University of Amsterdam, The Netherlands.
¹² McConnell Brain Imaging Center, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
¹³ Department of Neuroscience & The Ernest J. Del Monte Institute for Neuroscience, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
¹⁴ Amsterdam UMC, Department of Psychiatry, Amsterdam Institute for Addiction Research, University of Amsterdam, Amsterdam, The Netherlands.
¹⁵ Department of Research and Quality of Care, Arkin Mental Health Care, Amsterdam, The Netherlands.
¹⁶ Melbourne School of Psychological Sciences, University of Melbourne, Melbourne, Victoria, Australia.
¹⁷ Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO, USA.
¹⁸ Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO, USA.
¹⁹ Jane and Terry Semel Institute of Neuroscience and Human Behavior, David Geffen School of Medicine, Universityof California at Los Angeles, Los Angeles, CA, USA.
²⁰ School of Psychology, Faculty of Health Sciences, Australian Catholic University, Melbourne, Victoria, Australia.
²¹ Behavioural Science Institute, Radboud University, Nijmegen, The Netherlands.
²² Olin Neuropsychiatry Research Center, Hartford Hospital/IOL, Hartford, CT, USA.
²³ Clinical NeuroImaging Research Core, Division of Intramural Clinical and BiologicalResearch, National Institute of Alcohol Abuse and Alcoholism, Bethesda, MD, USA.
²⁴ VA San Diego Healthcare System and Department of Psychiatry, University of California San Diego, CA, USA.
²⁵ Laureate Institute for Brain Research, Tulsa, OK, USA.
²⁶ Department of Radiology and Nuclear Medicine, Amsterdam UMC, location AMC, Amsterdam, The Netherlands.
²⁷ Orygen, The National Centre of Excellence in Youth Mental Health, Parkville, Australia.
²⁸ Centre for Youth Mental Health, The University of Melbourne, Parkville, Australia.
²⁹ School of Psychology and Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, New South Wales, Australia.
³⁰ The Australian Centre for Cannabinoid Clinical and Research Excellence (ACRE), New Lambton Heights, New South Wales, Australia.
³¹ SA MRC Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
³² Department of Psychiatry and Mental Health, Faculty of Health Sciences University of Cape Town, South Africa.
³³ Department of Psychiatry, University of Amsterdam, Amsterdam, The Netherlands.
³⁴ Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands.
³⁵ Addiction Development and Psychopathology (ADAPT) Lab, University of Amsterdam, Amsterdam, The Netherlands.
³⁶ Department of Psychiatry, Université de Montreal, CHU Ste Justine Hospital, Canada.

PMID: 31746534
PMCID: PMC7237314
DOI: 10.1111/adb.12830

Abstract

While imaging studies have demonstrated volumetric differences in subcortical structures associated with dependence on various abused substances, findings to date have not been wholly consistent. Moreover, most studies have not compared brain morphology across those dependent on different substances of abuse to identify substance-specific and substance-general dependence effects. By pooling large multinational datasets from 33 imaging sites, this study examined subcortical surface morphology in 1628 nondependent controls and 2277 individuals with dependence on alcohol, nicotine, cocaine, methamphetamine, and/or cannabis. Subcortical structures were defined by FreeSurfer segmentation and converted to a mesh surface to extract two vertex-level metrics-the radial distance (RD) of the structure surface from a medial curve and the log of the Jacobian determinant (JD)-that, respectively, describe local thickness and surface area dilation/contraction. Mega-analyses were performed on measures of RD and JD to test for the main effect of substance dependence, controlling for age, sex, intracranial volume, and imaging site. Widespread differences between dependent users and nondependent controls were found across subcortical structures, driven primarily by users dependent on alcohol. Alcohol dependence was associated with localized lower RD and JD across most structures, with the strongest effects in the hippocampus, thalamus, putamen, and amygdala. Meanwhile, nicotine use was associated with greater RD and JD relative to nonsmokers in multiple regions, with the strongest effects in the bilateral hippocampus and right nucleus accumbens. By demonstrating subcortical morphological differences unique to alcohol and nicotine use, rather than dependence across all substances, results suggest substance-specific relationships with subcortical brain structures.

Keywords: addiction; structural MRI; substance dependence.

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Figures

**Fig. 1.. Overview of the vertex-wise shape metrics employed.**
**(A)** 3D model of subcortical structures within the brain space. **(B)** The radial distance (RD) of a structure corresponds to the distance between each surface vertex and the structure’s medial skeleton. **(C)** The Jacobian determinant (JD) corresponds to the deformation necessary to match the subject-specific structure to a template. A higher JD reflects a larger ‘surface area’ relative to the template.

**Fig. 2.. Subcortical difference between individuals with substance dependence and non-dependent controls.**
Bottom and top view of (i) local surface thickness (radial distance, RD) and (ii) local area (natural logarithm of the Jacobian determinant, JD) differences across subcortical structures in the left (left) and right hemispheres (right), in individuals with substance dependence compared to non-dependent controls. All effects controlled for imaging site, sex, and age. Heat maps represent beta-values of the significant regions in each split half (SPLIT 1 and SPLIT 2). Overlap in significance across both splits are colored in blue in the last column (OVERLAP).

**Fig. 3.. Subcortical difference between individuals with alcohol dependence and non-dependent controls.**
Bottom and top view of (i) local surface thickness (radial distance, RD) and (ii) local area (natural logarithm of the Jacobian determinant, JD) differences across subcortical structures in the left (left) and right hemispheres (right), in individuals with an alcohol dependence (AlcD) compared to non-dependent controls. All effects controlled for imaging site, sex, and age. Heat maps represent beta-values of the significant regions in each split half (SPLIT 1 and SPLIT 2). Overlap in significance across both splits are colored in blue in the last column (OVERLAP).

**Fig. 4.. Subcortical difference between individuals with nicotine dependence and non-smoking controls.**
Bottom and top view of (i) local surface thickness (radial distance, RD) and (ii) local area (natural logarithm of the Jacobian determinant, JD) differences across subcortical structures in the left (left) and right hemispheres (right), in individuals with a nicotine dependence (NicD) compared to non-smoking controls. All effects controlled for imaging site, sex, and age. Heat maps represent beta-values of the significant regions in each split half (SPLIT 1 and SPLIT 2). Overlap in significance across both splits are colored in blue in the last column (OVERLAP).

**Fig. 5.. Subcortical difference between smoking controls and non-smoking controls.**
Bottom and top view of (i) local surface thickness (radial distance, RD) and (ii) local area (natural logarithm of the Jacobian determinant, JD) differences across subcortical structures in the left (left) and right hemispheres (right), in smoking controls compared to non-smoking controls. All effects controlled for imaging site, sex, and age. Heat maps represent beta-values of the significant regions in each split half (SPLIT 1 and SPLIT 2). Overlap in significance across both splits are colored in blue in the last column (OVERLAP).

See this image and copyright information in PMC

References

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Subcortical surface morphometry in substance dependence: An ENIGMA addiction working group study

Affiliations

Subcortical surface morphometry in substance dependence: An ENIGMA addiction working group study

Authors

Affiliations

Abstract

Figures

References

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MeSH terms

Substances

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LinkOut - more resources

Full Text Sources

Medical

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