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Towards personalized medicine: subtyping using functional profiles

Neuropsychopharmacology volume 49, pages 347–348 (2024)Cite this article

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Rates of Substance Use Disorders (SUDs) are at an all-time high, especially in the United States. Notably, a low percentage of individuals with SUDs seek available treatments, due at least in part to low confidence in treatment effectiveness and prior negative experiences. Psychiatric illnesses, including SUDs, are vastly complex [1], with many underlying neurobehavioral mechanisms that each may contribute to a different degree in different individuals with the same psychiatric illness, which has been termed the ‘heterogeneity problem’ [2]. This makes it unlikely that a single treatment will effectively treat all individuals with the same psychiatric illness. Therefore, understanding how profiles of behavioral and neural function vary from individual to individual within a diagnostic group is critical for advancing our ability to develop effective treatments.

We refer to our approach as ‘mechanism-based’ subtyping, in contrast to ‘symptom-based’ subtyping approaches that have often been employed in the past. Among the over 120 addiction subtyping studies published since 1981, the vast majority identified subtypes using data assessing clinical symptom severity rather than underlying functional mechanisms. Unfortunately, symptom-based subtyping approaches have proven ineffective for defining functional targets that are necessary for the development of tailored addiction treatments. In contrast, ‘mechanism-based’ subtyping can provide such treatment targets, bringing a personalized medicine approach within grasp. For example, in a post-randomized controlled trial analysis, individuals with Alcohol Use Disorder were grouped into people who drank to relieve negative emotions versus to experience pleasure. Not surprisingly, only the individuals that drank to experience pleasure were successfully treated with the ‘pleasure-reducing’ medication naltrexone [5].

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Fig. 1: The emergence of subtypes.

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Acknowledgements

We would like to thank Andrea M. Maxwell and Leyla R. Brucar for their comments.

Funding

GD is supported by a grant from the National Institute on Drug Abuse (5T32DA007234-29). AZ is supported by a grant from the National Institute on Alcohol Abuse and Alcoholism (RO1AA029406). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Authors and Affiliations

  1. Graduate Program in Neuroscience, University of Minnesota, Minneapolis, MN, USA

    Gunner Drossel

  2. Department of Psychiatry and Behavioral Sciences, University of Minnesota, Minneapolis, MN, USA

    Gunner Drossel & Anna Zilverstand

  3. Medical Discovery Team on Addiction, University of Minnesota, Minneapolis, MN, USA

    Anna Zilverstand

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  1. Gunner Drossel
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  2. Anna Zilverstand
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GD and AZ wrote the manuscript and prepared the figure.

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Correspondence to Anna Zilverstand.

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The authors declare no competing interests.

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Drossel, G., Zilverstand, A. Towards personalized medicine: subtyping using functional profiles. Neuropsychopharmacol. 49, 347–348 (2024). https://doi.org/10.1038/s41386-023-01704-2

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