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Psychosis superspectrum II: neurobiology, treatment, and implications

Molecular Psychiatry (2024)Cite this article

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Abstract

Alternatives to traditional categorical diagnoses have been proposed to improve the validity and utility of psychiatric nosology. This paper continues the companion review of an alternative model, the psychosis superspectrum of the Hierarchical Taxonomy of Psychopathology (HiTOP). The superspectrum model aims to describe psychosis-related psychopathology according to data on distributions and associations among signs and symptoms. The superspectrum includes psychoticism and detachment spectra as well as narrow subdimensions within them. Auxiliary domains of cognitive deficit and functional impairment complete the psychopathology profile. The current paper reviews evidence on this model from neurobiology, treatment response, clinical utility, and measure development. Neurobiology research suggests that psychopathology included in the superspectrum shows similar patterns of neural alterations. Treatment response often mirrors the hierarchy of the superspectrum with some treatments being efficacious for psychoticism, others for detachment, and others for a specific subdimension. Compared to traditional diagnostic systems, the quantitative nosology shows an approximately 2-fold increase in reliability, explanatory power, and prognostic accuracy. Clinicians consistently report that the quantitative nosology has more utility than traditional diagnoses, but studies of patients with frank psychosis are currently lacking. Validated measures are available to implement the superspectrum model in practice. The dimensional conceptualization of psychosis-related psychopathology has implications for research, clinical practice, and public health programs. For example, it encourages use of the cohort study design (rather than case-control), transdiagnostic treatment strategies, and selective prevention based on subclinical symptoms. These approaches are already used in the field, and the superspectrum provides further impetus and guidance for their implementation. Existing knowledge on this model is substantial, but significant gaps remain. We identify outstanding questions and propose testable hypotheses to guide further research. Overall, we predict that the more informative, reliable, and valid characterization of psychopathology offered by the superspectrum model will facilitate progress in research and clinical care.

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Fig. 1: Utility of HiTOP for development of animal models.
Fig. 2: Illustrative profile diagnosis of a patient with psychosis.

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No empirical data was generated in this literature review.

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Acknowledgements

The authors thank Di Wang for important help in preparation of this paper.

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Authors and Affiliations

  1. Department of Psychiatry and Behavioral Health, Stony Brook University, Stony Brook, NY, USA

    Roman Kotov & Katherine G. Jonas

  2. Department of Psychiatry, University of Maryland, Baltimore, MD, USA

    William T. Carpenter

  3. Department of Psychology, University of North Texas, Denton, TX, USA

    David C. Cicero

  4. Department of Psychiatry, The Zucker Hillside Hospital, Northwell Health, Glen Oaks, NY, USA

    Christoph U. Correll

  5. Department of Psychiatry and Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA

    Christoph U. Correll

  6. Department of Child and Adolescent Psychiatry, Charité - Universitätsmedizin Berlin, Berlin, Germany

    Christoph U. Correll

  7. Department of Psychological Science, University of California, Irvine, Irvine, CA, USA

    Elizabeth A. Martin

  8. Department of Psychiatry, University of California San Diego, La Jolla, CA, USA

    Jared W. Young

  9. Research Service, VA San Diego Healthcare System, San Diego, CA, USA

    Jared W. Young

  10. Rutgers University, The State University of New Jersey, New Brunswick, NJ, USA

    David H. Zald

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Contributions

RK and KGJ conceptualized the study. Each author conducted a portion of the literature review, wrote the first draft of the corresponding section, critically revised the entire manuscript drafts, and approved the final version.

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Correspondence to Roman Kotov.

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Competing interests

This research was supported by the National Institute of Mental Health: R01MH122537 (R Kotov). CUC has been a consultant and/or advisor to or has received honoraria from: AbbVie, Acadia, Alkermes, Allergan, Angelini, Aristo, Boehringer-Ingelheim, Cardio Diagnostics, Cerevel, CNX Therapeutics, Compass Pathways, Darnitsa, Gedeon Richter, Hikma, Holmusk, IntraCellular Therapies, Janssen/J&J, Karuna, LB Pharma, Lundbeck, MedAvante-ProPhase, MedInCell, Merck, Mindpax, Mitsubishi Tanabe Pharma, Mylan, Neurocrine, Newron, Noven, Novo Nordisk, Otsuka, Pharmabrain, PPD Biotech, Recordati, Relmada, Reviva, Rovi, Seqirus, SK Life Science, Sunovion, Sun Pharma, Supernus, Takeda, Teva, and Viatris. He provided expert testimony for Janssen and Otsuka. He served on a Data Safety Monitoring Board for Compass, Lundbeck, Relmada, Reviva, Rovi, Supernus, and Teva. He has received grant support from Janssen and Takeda. He received royalties from UpToDate and is also a stock option holder of Cardio Diagnostics, Mindpax, LB Pharma and Quantic.

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Kotov, R., Carpenter, W.T., Cicero, D.C. et al. Psychosis superspectrum II: neurobiology, treatment, and implications. Mol Psychiatry (2024). https://doi.org/10.1038/s41380-024-02410-1

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