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Neuroimaging of reward mechanisms in Gambling disorder: an integrative review

Molecular Psychiatry volume 24, pages 674–693 (2019)Cite this article

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Abstract

Gambling disorder (GD) was reclassified as a behavioral addiction in the DSM-5 and shares clinical and behavioral features with substance use disorders (SUDs). Neuroimaging studies of GD hold promise in isolating core features of the addiction syndrome, avoiding confounding effects of drug neurotoxicity. At the same time, a neurobiologically-grounded theory of how behaviors like gambling can become addictive remains lacking, posing a significant hurdle for ongoing decisions in addiction nosology. This article integrates research on reward-related brain activity (functional MRI) and neurotransmitter function (PET) in GD, alongside the consideration of structural MRI data as to whether these signals more likely reflect pre-existing vulnerability or neuroadaptive change. Where possible, we point to qualitative similarities and differences with established markers for SUDs. Structural MRI studies indicate modest changes in regional gray matter volume and diffuse reductions in white matter integrity in GD, contrasting with clear structural deterioration in SUDs. Functional MRI studies consistently identify dysregulation in reward-related circuitry (primarily ventral striatum and medial prefrontal cortex), but evidence is mixed as to the direction of these effects. The need for further parsing of reward sub-processes is emphasized, including anticipation vs outcome, gains vs. losses, and disorder-relevant cues vs natural rewards. Neurotransmitter PET studies indicate amplified dopamine (DA) release in GD, in the context of minimal differences in baseline DA D2 receptor binding, highlighting a distinct profile from SUDs. Preliminary work has investigated further contributions of opioids, GABA and serotonin. Neuroimaging data increasingly highlight divergent profiles in GD vs. SUDs. The ability of gambling to perpetually activate DA (via maximal uncertainty) may contribute to neuroimaging similarities between GD and SUDs, whereas the supra-physiological DA effects of drugs may partly explain differences in the neuroimaging profile of the two syndromes. Coupled with consistent observations of correlations with gambling severity and related clinical variables within GD samples, the overall pattern of effects is interpreted as a likely combination of shared vulnerability markers across GD and SUDs, but with further experience-dependent neuroadaptive processes in GD.

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Acknowledgements

Support for this work was provided by a Grant-in-Aid from Okanagan College, Kelowna BC, Canada. The Province of British Columbia government and the British Columbia Lottery Corporation (BCLC) had no involvement in the ideas expressed herein, and impose no constraints on publishing.

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Authors and Affiliations

  1. Centre for Gambling Research, University of British Columbia (UBC), Vancouver, BC, Canada

    Luke Clark

  2. Department of Psychology, University of British Columbia, Vancouver, BC, Canada

    Luke Clark

  3. Addiction Imaging Research Group, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada

    Isabelle Boileau

  4. Vivian M. Rakoff PET Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada

    Isabelle Boileau

  5. Addictions Program, Centre for Addiction and Mental Health, Toronto, ON, Canada

    Isabelle Boileau

  6. Schizophrenia Program, Centre for Addiction and Mental Health, Toronto, ON, Canada

    Isabelle Boileau

  7. Department of Psychiatry, University of Toronto, Toronto, ON, Canada

    Isabelle Boileau

  8. Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada

    Isabelle Boileau & Martin Zack

  9. Clinical Neuroscience Program, Centre for Addiction and Mental Health, Toronto, ON, Canada

    Martin Zack

  10. Department of Pharmacology & Toxicology, University of Toronto, Toronto, ON, Canada

    Martin Zack

  11. Department of Public Health Sciences, University of Toronto, Toronto, ON, Canada

    Martin Zack

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Correspondence to Martin Zack.

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Conflict of interest

LC is the Director of the Centre for Gambling Research at UBC, which is supported by funding from the Province of British Columbia and the British Columbia Lottery Corporation (BCLC), a Canadian Crown Corporation. LC receives funding from the Natural Sciences and Engineering Research Council (Canada). LC has received a speaker/travel honorarium from Svenska Spel (Sweden) and an award from the National Center for Responsible Gaming (US). He has not received any further direct or indirect payments from the gambling industry or groups substantially funded by gambling. He has provided paid consultancy to, and received royalties from, Cambridge Cognition Ltd. relating to neurocognitive testing. IB holds operating grants from the Canadian Institutes of Health Research and National Institutes of Health and declares no conflict of interest. MZ holds an operating grant from The National Center for Responsible Gaming (US).

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Clark, L., Boileau, I. & Zack, M. Neuroimaging of reward mechanisms in Gambling disorder: an integrative review. Mol Psychiatry 24, 674–693 (2019). https://doi.org/10.1038/s41380-018-0230-2

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