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Neuroimaging biomarkers of addiction

Nature Mental Health volume 2, pages 1498–1517 (2024)Cite this article

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Abstract

As a neurobiological process, addiction involves pathological patterns of engagement with substances and a range of behaviors with a chronic and relapsing course. Neuroimaging technologies assess brain activity, structure, physiology, and metabolism at scales ranging from neurotransmitter receptors to large-scale brain networks, providing unique windows into the core neural processes implicated in substance use disorders. Identified aberrations in the neural substrates of reward and salience processing, response inhibition, interoception, and executive functions with neuroimaging can inform the development of pharmacological, neuromodulatory, and psychotherapeutic interventions to modulate the disordered neurobiology. Closed- or open-loop interventions can integrate these biomarkers with neuromodulation in real time or offline to personalize stimulation parameters and deliver precise intervention. This Analysis provides an overview of neuroimaging modalities in addiction medicine, potential neuroimaging biomarkers, and their physiologic and clinical relevance. Future directions and challenges in bringing these putative biomarkers from the bench to the bedside are also discussed.

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Fig. 1: Distribution of the neuroimaging protocols based on year and substance.
Fig. 2: Characteristics of neuroimaging outcome measures across registered trials and meta-analyses.
Fig. 3: Schematic representation of stages in substance use and SUDs and their therapeutic interventions and corresponding biomarker types.
Fig. 4: Putative neuroimaging biomarkers reported in registered protocols in various SUDs and neuroimaging modalities.
Fig. 5: Multi-scale brain aberrations as putative neuroimaging biomarkers in trials for SUDs.
Fig. 6: Major steps in the development and validation of potential neuroimaging biomarkers for SUDs.

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Data availability

The protocol and data for this systematic review are available on the open science framework (OSF) website (https://osf.io/79uc3/?view_only=1d92a6fd769f40119464b156f0c88912). The ClinicalTrials.gov search engine was used through the Study Fields query URL (https://ClinicalTrials.gov/api/gui/ref/api_urls) for searching the clinical trial protocols. For full-text screening, all available records were downloaded from the Aggregate Analysis of ClinicalTrials.gov (AACT) Database, Clinical Trials Transformation Initiative (CTTI) database203 (https://aact.ctti-clinicaltrials.org/) for the second stage. For searching the systematic reviews and meta-analyses, studies were identified using the Medline/PubMed database (https://pubmed.ncbi.nlm.nih.gov/).

Code availability

All codes are available on the study’s OSF project repository at the following link: https://osf.io/79uc3/?view_only=1d92a6fd769f40119464b156f0c88912. Data analyses and illustrations were conducted using R version 4.0.5204, with dplyr205 and ggplot2206 packages. The codes for data illustrations are freely available on the OSF repository of this project.

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Acknowledgments

The authors thank G. Soleimani, M. Farhadi and M. Ebrahimi for their contribution to designing some of the figures. H.E. is supported by funds from the Laureate Institute for Brain Research and Medical Discovery Team on Addiction and Brain Behavior Foundation (NARSAD Young Investigator Award 27305). O.C. is funded by NIH grants AG07425801, AG077497, AG077000, AG067765, AG041200, AG062309, AG062200, and AG069476, William K. Warren Foundation and the National Institute of General Medical Sciences Center Grant award number 1P20GM121312, and the National Institute on Drug Abuse (U01DA050989). A.R.C. is funded by NIH/NIDA mechanisms UG1DA050209, R01DA039215, T32-DA-028874, P30 DA046345, and U01DA048517. T.R. was substantially involved in UG1DA050209 and U01DA048517 consistent with her role as scientific officer. She has no substantial involvement in the other cited grants. The views and opinions expressed in this manuscript are those of the authors only and do not necessarily represent the views, official policy, or position of the US Department of Health and Human Services or any of its affiliated institutions or agencies.

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Authors and Affiliations

  1. Department of Psychiatry, University of Minnesota Medical School, Minneapolis, MN, USA

    Hamed Ekhtiari

  2. Laureate Institute for Brain Research (LIBR), Tulsa, OK, USA

    Hamed Ekhtiari & Martin P. Paulus

  3. School of Psychological Sciences, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia

    Arshiya Sangchooli

  4. Pennington Biomedical Research Center, Baton Rouge, LA, USA

    Owen Carmichael

  5. Institute for Drug and Alcohol Studies, Virginia Commonwealth University, Richmond, VA, USA

    F. Gerard Moeller

  6. Translational Medicine, Sage Therapeutics, Cambridge, MA, USA

    Patricio O’Donnell

  7. Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, MA, USA

    Patricio O’Donnell

  8. Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Maria A. Oquendo & Anna Rose Childress

  9. Center for Depression, Anxiety and Stress Research, McLean Hospital, Belmont, MA, USA

    Diego A. Pizzagalli

  10. Harvard Medical School, Boston, MA, USA

    Diego A. Pizzagalli

  11. National Institute on Drug Abuse, Bethesda, MD, USA

    Tatiana Ramey

  12. Department of Psychiatry, University of Colorado Anschutz Medical Campus, Aurora, CO, USA

    Joseph P. Schacht

  13. Iranian National Center for Addiction Studies (INCAS), Tehran University of Medical Sciences, Tehran, Iran

    Mehran Zare-Bidoky

  14. Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC, USA

    Kathleen Brady

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  1. Hamed Ekhtiari
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  2. Arshiya Sangchooli
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Contributions

K.B., O.C., A.R.C., H.E., F.G.M., P.O., M.O., M.P.P., D.A.P., T.R., and J.S. conceived of the presented idea and designed the study, and H.E. coordinated the consensus process among all authors. A.S., M.Z.-B., and H.E. gathered data, designed the tables, and performed the initial analytic calculations. All authors discussed the results and contributed to the final manuscript.

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Correspondence to Hamed Ekhtiari.

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Competing interests

O.C. has received grant funding from Eli Lilly and Nestle. He has provided paid consulting to Novo Nordisk. Over the past 3 years, D.A.P. has received consulting fees from Boehringer Ingelheim, Compass Pathways, Engrail Therapeutics, Neumora Therapeutics (formerly BlackThorn Therapeutics), Neurocrine Biosciences, Neuroscience Software, Sage Therapeutics, Sama Therapeutics and Takeda; he has received honoraria from the American Psychological Association, Psychonomic Society and Springer (for editorial work) and from Alkermes; he has received research funding from the BIRD Foundation, Brain and Behavior Research Foundation, Dana Foundation, DARPA, Millennium Pharmaceuticals, NIMH and Wellcome Leap MCPsych; and he has received stock options from Compass Pathways, Engrail Therapeutics, Neumora Therapeutics and Neuroscience Software. M.P.P. is an adviser to Spring Care, a behavioral health startup; he has received royalties for an article about methamphetamine in UpToDate and he has a consulting agreement with, and receives compensation from, F. Hoffmann–La Roche. P.O. is an employee and shareholder of Sage Therapeutics. All other authors declare no competing interests.

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Nature Mental Health thanks Yavin Shaham and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Supplementary Figs. 1–3, Tables 1–3 and Methods.

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Ekhtiari, H., Sangchooli, A., Carmichael, O. et al. Neuroimaging biomarkers of addiction. Nat. Mental Health 2, 1498–1517 (2024). https://doi.org/10.1038/s44220-024-00334-x

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