Towards precision psychiatry: initial foundations and future directions

Precision psychiatry, which uses biomarkers such as electroencephalography, functional magnetic resonance imaging, and peripheral biomarkers to align treatments with neural biology, could refine clinical trial design and improve outcomes in psychiatric drug discovery, according to a Perspective in Nature Reviews Drug Discovery. Proof-of-concept successes in postpartum depression and schizophrenia highlight the potential of stratified trials, though regulatory, commercial, and clinical considerations remain for integrating scalable biomarkers into drug development.

Abstract Psychiatric disorders carry a major public health burden, yet advances in treatment have been slow to emerge, partly owing to reliance on traditional symptom-based diagnostic frameworks. In this Perspective, we explore the emerging paradigm of precision psychiatry, which seeks to align therapeutic development with underlying neural biology dysfunctions using biomarkers. Drawing lessons from the success of precision oncology and neurology, precision psychiatry utilizes patient-specific biological measures of brain function — such as electroencephalography, objective behavioural assessments, functional magnetic resonance imaging and peripheral biomarkers — to understand drugs’ effects on the brain, define indications and stratify patient populations for targeted intervention development. We discuss mechanistic approaches that focus on excitation–inhibition balance, reward and aversion circuits, hippocampal–prefrontal neuroplasticity, and processing of social cues, highlighting how these frameworks can elucidate drug mechanisms and predict treatment responses. Proof-of-concept examples, including predictors of response to standard-of-care treatments, and patient subgroup-driven successes in postpartum depression and schizophrenia, underscore the potential of stratified trials to reduce development risks and improve clinical outcomes. We address ongoing and future regulatory, commercial and clinical considerations for integrating scalable and reproducible biomarkers into drug development. Precision psychiatry thus represents a new strategy to refine clinical trial design and develop biology-defined treatments, which may help to overcome longstanding challenges in psychiatric drug discovery. This is a preview of subscription content, access via your institution https://wayf.springernature.com?redirect uri=https%3A%2F%2Fwww.nature.com%2Farticles%2Fs41573-026-01509-0 Access options Access Nature and 54 other Nature Portfolio journals Get Nature+, our best-value online-access subscription 27,99 € / 30 days cancel any time Subscribe to this journal Receive 12 print issues and online access 269,00 € per year only 22,42 € per issue Buy this article - Purchase on SpringerLink - Instant access to the full article PDF. 39,95 € Prices may be subject to local taxes which are calculated during checkout Similar content being viewed by others References FDA-NIH Biomarker Working Group. BEST Biomarkers, EndpointS, and Other Tools Resource online https://www.ncbi.nlm.nih.gov/books/NBK326791/ https://www.ncbi.nlm.nih.gov/books/NBK326791/ FDA, 2016 .Rockoff, J. D. & Loftus, P. Bristol-Myers bucks trend toward precision medicine. 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Author information Authors and Affiliations Contributions The authors contributed equally to all aspects of the article. Corresponding author Ethics declarations Competing interests A.E. and P.O. receive salary from Alto Neuroscience. A.E., P.O. and H.M. hold equity in Alto Neuroscience. H.M. holds equity in Johnson & Johnson. He is Scientific Advisory Board member, Board member, strategic adviser and/or consultant past 5 years for: Stanley Center, Dana Foundation, Healthy Brains Global Initiative, McLean Hospital, Foundation for OCD, Dolby Family Ventures, Vanna Health, Alto Neuroscience, Noema, Otsuka, Boehringer-Ingelheim, Sanofi, Apollo Therapeutics, Freedom Biosciences, Empyrean, Lundbeck, Psychogenics and Rapport Therapeutics. K.J.R. has performed scientific consultation for Bioxcel, Bionomics, Acer and Jazz Pharma; serves on Scientific Advisory Boards for Sage, Boehringer Ingelheim, Senseye and the Brain Research Foundation; and has received sponsored research support from Alto Neuroscience. Peer review Peer review information Nature Reviews Drug Discovery thanks Mirko Manchia, Seth Hopkins and the other, anonymous, reviewer s for their contribution to the peer review of this work. Additional information Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Rights and permissions Springer Nature or its licensor e.g. a society or other partner holds exclusive rights to this article under a publishing agreement with the author s or other rightsholder s ; author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. About this article Cite this article Etkin, A., O’Donnell, P., Ressler, K.J. et al. Towards precision psychiatry: initial foundations and future directions. Nat Rev Drug Discov 2026 . https://doi.org/10.1038/s41573-026-01509-0 Accepted: Published: Version of record: DOI: https://doi.org/10.1038/s41573-026-01509-0