Network-based modeling of brain-wide alterations in substance use disorders (ENIGMA)
Poster No:
1370
Submission Type:
Abstract Submission
Authors:
Beatrice Milano1, Foivos Georgiadis2, Sara Larivière3, Sophia Thomopoulos4, Paul Thompson4, Scott Mackey5, Patricia Conrod6, Hugh Garavan5, Sofie Valk7, Boris Bernhardt8, Matthias Kirschner9
Institutions:
1University of Geneva, Geneva, Switzerland, 2UZH-University of Zurich, Zurich , Switzerland, 3Université de Sherbrooke, Sherbrooke, QC, 4University of Southern California, Los Angeles, CA, 5University of Vermont College of Medicine, Burlington, VT, 6University of Montreal, Montreal, Quebec, 7Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Saxony, 8McGill University, Montreal, Quebec, 9HUG-Hôpitaux Universitaires Genève, Genève, Switzerland
First Author:
Co-Author(s):
Introduction:
Substance use disorders (SUD) are increasingly recognized as network disorders, characterised by system-wide structural brain alterations (Joutsa et al., 2022). Network mechanisms have been shown to influence the spatial patterning of morphometric alterations in neuropsychiatric conditions (Fornito et al., 2015); however, their contribution in SUD remains unclear. Here, we investigated how the underlying brain network architecture shapes morphometric alterations in SUD, compared such alterations across other six psychiatric disorders (Hansen et al., 2022a), and examined how neurotransmitter systems (Hansen, et al., 2022b) may be informative in such context.
Methods:
We examined cortical thickness and subcortical volume differences in 2312 individuals with different types of SUD (alcohol, amphetamines, cannabis, cocaine, nicotine, opioids) compared to 1951 non-affected individuals from the ENIGMA Addiction consortium (Thompson et al., 2020), controlling for age and sex. Additionally, analyses in each SUD type were performed to assess generalizability of our findings. Using normative resting-state fMRI and diffusion MRI connectivity data from the Human Connectome Project (n=207)(Van Essen et al., 2012), we evaluated SUD-related brain-wide morphometric alterations against two network susceptibility models: (i) hub vulnerability, assessing the relationship between regional network centrality and disease-related alterations, and (ii) epicenter mapping, identifying regions whose typical connectivity profiles closely resemble the morphological changes seen in SUD.
We sought to determine whether the network patterns observed in SUD reflect transdiagnostic features shared across psychiatric disorders or are disorder-specific. For this, we conducted cross-disorder comparisons using ENIGMA meta-analytic cortical and subcortical maps for Autism, ADHD, bipolar disorder, major depressive disorder, obsessive compulsive disorder, and schizophrenia.
Furthermore, we explored whether the identified functional and structural epicenters are linked to specific neurotransmitter systems.
We sought to determine whether the network patterns observed in SUD reflect transdiagnostic features shared across psychiatric disorders or are disorder-specific. For this, we conducted cross-disorder comparisons using ENIGMA meta-analytic cortical and subcortical maps for Autism, ADHD, bipolar disorder, major depressive disorder, obsessive compulsive disorder, and schizophrenia.
Furthermore, we explored whether the identified functional and structural epicenters are linked to specific neurotransmitter systems.
Results:
We identified widespread reductions in cortical thickness and subcortical volumes in individuals with SUD compared to controls. Cortical alterations were associated with higher cortico-cortical and subcortico-cortical degree centrality, underscoring hub vulnerability across all SUD types, especially in the alcohol subgroup. Functional connectivity epicenters encompassed regions in the parieto-temporal, frontal, and widespread subcortical areas (FDR p-values < 0.01), while structural epicenters were more restricted to sensory and parietal cortices, as well as the striatum and thalamus (FDR p-values < 0.01) (Fig. 1).
Functional and structural connectivity cross-disorder analyses revealed strong correlations and significant overlaps between SUD and schizophrenia (rfunc = 0.88, rstruc = 0.73, pspin < 0.05), and between SUD and bipolar disorder (rfunc = 0.76, pspin < 0.05), highlighting shared network hubs.
The overlap between neurotransmitter receptor distributions and the significant functional and structural epicenters was mostly found in the cingulate and frontal gyrus cortices. Specifically, 5HT1b, GABAa (functional), and 5HTT, DAT, D1, and NMDA (structural) (Fig. 2).
Functional and structural connectivity cross-disorder analyses revealed strong correlations and significant overlaps between SUD and schizophrenia (rfunc = 0.88, rstruc = 0.73, pspin < 0.05), and between SUD and bipolar disorder (rfunc = 0.76, pspin < 0.05), highlighting shared network hubs.
The overlap between neurotransmitter receptor distributions and the significant functional and structural epicenters was mostly found in the cingulate and frontal gyrus cortices. Specifically, 5HT1b, GABAa (functional), and 5HTT, DAT, D1, and NMDA (structural) (Fig. 2).
·SUD epicenters and neurotransmitter receptors analysis
·Cross-disorder cortical epicenter maps comparison between each SUD and ADHD, autism, bipolar disorder, major depressive disorder, obsessive compulsive disorder, and schizophrenia
Conclusions:
Structural and functional alterations in SUD are guided by normative brain network architecture, with marked involvement of hub regions and epicenters, whose connectivity profiles appear to show both unique and shared features across different SUD, highlighting differential vulnerability.
Additionally, we showed novel and expected associations between SUD abnormality patterns across different psychiatric disorders and neurotransmitter receptor distributions.
These findings may provide insights into the network mechanisms and neurotransmitter contributions underlying the spatial distribution of SUD-related structural alterations, offering potential and more precise targets for therapeutic interventions in SUD.
Additionally, we showed novel and expected associations between SUD abnormality patterns across different psychiatric disorders and neurotransmitter receptor distributions.
These findings may provide insights into the network mechanisms and neurotransmitter contributions underlying the spatial distribution of SUD-related structural alterations, offering potential and more precise targets for therapeutic interventions in SUD.
Disorders of the Nervous System:
Psychiatric (eg. Depression, Anxiety, Schizophrenia) 2
Modeling and Analysis Methods:
Connectivity (eg. functional, effective, structural)
fMRI Connectivity and Network Modeling 1
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Cortical Anatomy and Brain Mapping
Transmitter Receptors
Keywords:
Addictions
Computational Neuroscience
FUNCTIONAL MRI
Neurotransmitter
Psychiatric Disorders
RECEPTORS
STRUCTURAL MRI
Sub-Cortical
Other - Network neuroscience
1|2Indicates the priority used for review
Abstract Information
By submitting your proposal, you grant permission for the Organization for Human Brain Mapping (OHBM) to distribute your work in any format, including video, audio print and electronic text through OHBM OnDemand, social media channels, the OHBM website, or other electronic publications and media.
The Open Science Special Interest Group (OSSIG) is introducing a reproducibility challenge for OHBM 2025. This new initiative aims to enhance the reproducibility of scientific results and foster collaborations between labs. Teams will consist of a “source” party and a “reproducing” party, and will be evaluated on the success of their replication, the openness of the source work, and additional deliverables. Click here for more information. Propose your OHBM abstract(s) as source work for future OHBM meetings by selecting one of the following options:
Please indicate below if your study was a "resting state" or "task-activation” study.
Healthy subjects only or patients (note that patient studies may also involve healthy subjects):
Was this research conducted in the United States?
Were any human subjects research approved by the relevant Institutional Review Board or ethics panel? NOTE: Any human subjects studies without IRB approval will be automatically rejected.
Were any animal research approved by the relevant IACUC or other animal research panel? NOTE: Any animal studies without IACUC approval will be automatically rejected.
Please indicate which methods were used in your research:
Which processing packages did you use for your study?
Provide references using APA citation style.
Hansen, J. Y. (2022a). Local molecular and global connectomic contributions to cross-disorder cortical abnormalities. Nature Communications, 13(1), 4682.
Hansen, J. Y. (2022b). Mapping neurotransmitter systems to the structural and functional organization of the human neocortex. Nature Neuroscience, 25(11), 1569–1581.
Joutsa, J. (2022). Brain lesions disrupting addiction map to a common human brain circuit. Nature Medicine, 28(6), 1249–1255.
Thompson, P. M. (2020). ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries. Translational Psychiatry, 10(1), 100.
Van Essen, D. C. (2012). The Human Connectome Project: A data acquisition perspective. NeuroImage, 62(4), 2222–2231.