Research Spotlight: An expert-led roadmap to advance biomarkers in psychiatry

Kerry Ressler, MD, PHD, of McLean Hospital and the Department of Psychiatry at Mass General Brigham, is the senior author of a new consensus paper published in NPP—Digital Psychiatry and Neuroscience, “Toward actionable biomarkers in psychiatry: a collaborative roadmap for precision clinical trials. An ACNP position paper.”

Q: What challenges or unmet needs make this paper important?

Psychiatric drug and treatment development continues to face major challenges, including diagnostic heterogeneity (meaning that people with the same diagnosis can have very different underlying symptoms and biology), high placebo response rates and a lack of clearly defined mechanistic targets.

Unlike in other therapeutic areas of medicine, clinical trials in psychiatry still predominantly enroll patients based on symptom checklists rather than objective, measurable biological signs of disease (these signs are known as biomarkers). This approach makes it difficult to identify specific clinical populations and impedes the development of targeted treatments. It also stands in contrast to other areas of clinical neuroscience research. For instance, in Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis, researchers have conducted large-scale, unbiased and longitudinal studies. Those studies, coupled with biospecimen repositories and collaborative infrastructures, have generated useful stratification frameworks, validated biomarkers and novel hypotheses.

Lastly, the scale and complexity of discovering psychiatric biomarkers exceed what individual labs or companies can accomplish independently.

Q: What central question(s) were you investigating?

This position paper addresses three central questions:

• Why has the development of clinically actionable biomarkers in psychiatry lagged behind that of other therapeutic areas?

• What scientific, regulatory and structural barriers must be overcome to catch up?

• What coordinated actions across academia, industry and regulatory agencies are required to establish these biomarkers for transformational progress towards precision medicine in psychiatry?

Q: What are a few of the consensus paper’s key messages?

Psychiatry stands at a pivotal moment. The scientific tools needed to define biologically grounded, scalable biomarkers are now available, yet their translation into predictable mechanistic biomarkers and targets, clinical trials and regulatory decision-making remain fragmented.

As outlined in our roadmap, the principal barriers are not simply technical. There are structural and systemic barriers to address, including misaligned incentives, unclear contexts of use, insufficient standardization and the absence of sustained precompetitive infrastructure. We call on academic investigators, industry sponsors, regulators and funders to commit to a coordinated, precompetitive strategy for biomarker development in psychiatry, and provide strategies for doing so.

This includes converging on shared definitions and use cases, investing in rigorous prospective studies, systematically validating biomarkers across existing large cohorts, and engaging regulators early to shape feasible evidentiary pathways. Importantly, success will require valuing replication, negative findings and harmonization as highly as novelty.

By adopting this collective approach — modeled on successful frameworks in neurodegenerative disease but tailored to the unique complexity of psychiatric disorders — the field can transition from exploratory signals to regulatory-ready tools that meaningfully improve trial efficiency, therapeutic targeting and patient outcomes.

Overall, our findings emphasize that precision psychiatry will not emerge from isolated breakthroughs, but from a shift to sustained collaboration around shared standards, shared data and shared responsibility for translation and implementation.

Q: What are the real-world implications, particularly for patients?

New and emerging therapies, including combined uses of traditional medication, biologicals and neural circuit-targeted treatments, as well as targeted psychotherapies, rely on more precise diagnosis, subtyping and further biological understanding of psychiatric disorders. This will only be achievable with biomarkers that allow a more quantitative and predictive understanding of the underlying biology and biological subtypes of psychiatric disorders beyond our current diagnostic classifications.

Such progress will allow for more precise and optimized treatment and intervention for individual patients, improving efficacy and time to response.

Authorship: In addition to Ressler, Mass General Brigham authors include William A. Carlezon, Jr. Additional authors include Sahib S. Khalsa, Deanna Barch, Linda S. Brady, Teresa Buracchio, Christopher Chatham, Wayne C. Drevets, C. Neill Epperson, Amit Etkin, Bernard Fischer, Danielle L. Graham, Steven C. Hoffmann, Bashkim Kadriu, Martien J. H. Kas, Hartmuth Kolb, Marion Leboyer, Sarah H. Lisanby, Lauren Liss, Husseini K. Manji, Valentina Mantua, Hugh M. Marston, William Potter and Frank Yocca.

Paper cited: Khalsa, SS., et al. “Toward actionable biomarkers in psychiatry: a collaborative roadmap for precision clinical trials. An ACNP position paper.” NPP—Digital Psychiatry and Neuroscience. DOI: 10.1038/s44277-026-00069-w

Funding: Carlezon’s time spent on this manuscript was supported by grant MH063266. No other authors declare relevant funding sources related to this work.

Disclosures: Please see the paper for a full list of disclosures.

URL for CTA: https://doi.org/10.1038/s44277-026-00069-w