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Network-based modeling of brain-wide structural alterations in substance use disorders

Poster No:

2293 

Submission Type:

Abstract Submission 

Authors:

Foivos Georgiadis1, Sara Larivière2, Sophia Thomopoulos3, Paul Thompson4, Philipp Homan5, Scott Mackey6, Patricia Conrod7, Hugh Garavan8, Sofie Valk9, Boris Bernhardt10, Matthias Kirschner11, ENIGMA Addiction Working Group12

Institutions:

1University of Zurich, Zurich, Switzerland, 2Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, 3USC, Marina del Rey, CA, 4USC, Marina Del Rey, CA, 5Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric University Hospital Zurich, Zurich, Zurich, 6The University of Vermont, Burlington, VT, 7University of Montreal, Montreal, Quebec, 8University of Vermont, Burlington, VT, 9Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany, 10Montreal Neurological Institute and Hospital, Montreal, Quebec, 11Geneva University Hospitals (HUG), Thonex, Geneva, 12ENIGMA, International, International

First Author:

Foivos Georgiadis  
University of Zurich
Zurich, Switzerland

Co-Author(s):

Sara Larivière  
Brigham and Women’s Hospital, Harvard Medical School
Boston, MA
Sophia Thomopoulos  
USC
Marina del Rey, CA
Paul Thompson  
USC
Marina Del Rey, CA
Philipp Homan  
Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric University Hospital Zurich
Zurich, Zurich
Scott Mackey  
The University of Vermont
Burlington, VT
Patricia Conrod  
University of Montreal
Montreal, Quebec
Hugh Garavan  
University of Vermont
Burlington, VT
Sofie Valk  
Max Planck Institute for Human Cognitive and Brain Sciences
Leipzig, Germany
Boris Bernhardt  
Montreal Neurological Institute and Hospital
Montreal, Quebec
Matthias Kirschner  
Geneva University Hospitals (HUG)
Thonex, Geneva
ENIGMA Addiction Working Group  
ENIGMA
International, International

Introduction:

Substance use disorders (SUD) are increasingly recognized as network disorders (Joutsa et al., 2022; Ottino-González et al., 2022) and associated with system-wide structural brain alterations (Mackey et al., 2019). Though network mechanisms have been shown to guide the spatial patterning of structural alterations in psychiatric and neurodegenerative conditions, it remains to be established whether these associations are also seen in SUD. Here, we tested whether large-scale structural alterations in SUD relate to normative functional and structural connectome architecture.

Methods:

We generated cortical and subcortical case-control differences in SUD from 2,847 individuals with SUD (alcohol, methamphetamines, cocaine, opioids, cannabis, and nicotine) and 1,951 non-affected individuals of the ENIGMA Addiction consortium. Using normative rs-fMRI and diffusion MRI connectivity data from the Human Connectome Project (n=207), we evaluated structural alterations of SUD against two network susceptibility models: i) hub vulnerability, which examines associations between regional network centrality and magnitude of disease-related alterations; ii) epicenter mapping, which identify regions whose typical connectivity profile most closely resembles the disease-related morphological alterations.

Results:

We identified widespread reductions in cortical thickness and subcortical volume in individuals with SUD compared to non-affected controls (Fig 1a,b). SUD-related regional structural alterations were associated with higher functional and structural cortico-cortical and functional subcortico-cortical degree centrality (DC) (Fig 1c, all pspin<0.05). Functional connectivity epicenters encompassed multiple parieto-temporal and frontal areas as well as subcortical regions (Fig 1c). Structural connectivity epicenters were more circumscribed, and located in sensory and parietal cortical areas and striatum and thalamus (Fig 1c).
Supporting Image: OHBM_figure_addiction_networkmodeling.png
Supporting Image: OHBM_fig1_legend.png
 

Conclusions:

Our findings show that in SUD, hub regions are more vulnerable to structural alterations and that distinct subcortical and cortical connectivity profiles are linked to the spatial pattern of cortical alterations. Together, our study provides novel insights how network mechanisms may guide the spatial distribution of SUD-related structural alterations.

Disorders of the Nervous System:

Psychiatric (eg. Depression, Anxiety, Schizophrenia) 2

Modeling and Analysis Methods:

Connectivity (eg. functional, effective, structural)

Neuroanatomy, Physiology, Metabolism and Neurotransmission:

Cortical Anatomy and Brain Mapping

Novel Imaging Acquisition Methods:

Anatomical MRI 1

Keywords:

Addictions
Cortex
STRUCTURAL MRI
Sub-Cortical
Other - Brain Connectome, Hub Vulnerability, Epicenter Mapping

1|2Indicates the priority used for review

Provide references using author date format

Joutsa, J., Moussawi, K., Siddiqi, S. H., Abdolahi, A., Drew, W., Cohen, A. L., Ross, T. J., Deshpande, H. U., Wang, H. Z., Bruss, J., Stein, E. A., Volkow, N. D., Grafman, J. H., van Wijngaarden, E., Boes, A. D., & Fox, M. D. (2022). Brain lesions disrupting addiction map to a common human brain circuit. Nature Medicine, 28(6), Article 6. https://doi.org/10.1038/s41591-022-01834-y

Mackey, S., Allgaier, N., Chaarani, B., Spechler, P., Orr, C., Bunn, J., Allen, N. B., Alia-Klein, N., Batalla, A., Blaine, S., Brooks, S., Caparelli, E., Chye, Y. Y., Cousijn, J., Dagher, A., Desrivieres, S., Feldstein-Ewing, S., Foxe, J. J., Goldstein, R. Z., … ENIGMA Addiction Working Group. (2019). Mega-Analysis of Gray Matter Volume in Substance Dependence: General and Substance-Specific Regional Effects. The American Journal of Psychiatry, 176(2), 119–128. https://doi.org/10.1176/appi.ajp.2018.17040415

Ottino-González, J., Garavan, H., & ENIGMA-Addiction and IMAGEN consortiums. (2022). Brain structural covariance network differences in adults with alcohol dependence and heavy-drinking adolescents. Addiction (Abingdon, England), 117(5), 1312–1325. https://doi.org/10.1111/add.15772