Precision psychiatry roadmap: towards a biology-informed framework for mental disorders

Abstract

The current classification systems for mental disorders provide a uniform symptom-based language to describe and diagnose mental disorders. Clinicians use these classifications to communicate with their patients and colleagues, to treat patients, and when applicable, to request reimbursement from payers. In clinical research and drug development, diagnostic categories are used as enrollment criteria for clinical trials and to inform prescribing information for the appropriate use of therapeutic interventions. However, like other neuropsychiatric diseases, mental disorders arise from the biology of the brain and its bidirectional interaction with the environment. Current classification systems do not reflect this knowledge. With scientific progress in neuroscience, the time has come for global stakeholders to align research efforts to work toward integrating symptomatic, biological, and behavioral information into the definition of mental disorders to advance the development of effective treatments. The European College of Neuropsychopharmacology (ECNP), following the 2024 New Frontiers Meeting, is coordinating a global initiative to design and implement a Precision Psychiatry Roadmap. By mobilizing resources and harmonizing translational methodologies and datasets, the aim is to discuss, design, and implement an iterative framework that incorporates biology-informed evidence into symptom-based syndromes, allowing for more discovery and implementation of mechanism-based effective treatments for mental disorders.

Fig. 1. The vision of bringing precision to psychiatry requires both a continuously evolving framework incorporating scientific and technological advances, as well as a shift by the mental healthcare ecosystem to a clinically and biologically informed framework of diagnoses.

Not everything can happen in parallel, nor does it all have to happen sequentially. Initially, broad changes can be made, e.g., based on our understanding of the relationship between symptoms and behavior via brain circuits and systems. These will be driven, at least in part, by the rapidly emerging digital technologies that are revolutionizing our ability to collect, collate, and interpret complex data sets. As these foundations are put in place, the full power of the omics revolution can be unleashed and the complexity of the interaction with the environment understood and integrated into the envisioned framework.

Fig. 2. The graphic indicates examples of how a biomarker category and drug development use are related.

BEST Biomarker Category and Examples of Corresponding Drug Development Uses (FDA-NIH Biomarker Working Group, 2016).

Fig. 3. The PPR, as represented in this schema, has several workstreams that need to be initiated, coordinated, and integrated for the effective development of a more quantitative and biology-informed diagnostic framework.

Implementation and operational delivery of a continuously evolving biology-informed diagnostic framework requires global alignment on principles and procedures and building consensus on the predictive validity of the new biology-informed findings to improve patient stratification and treatment. This framework will evolve based on scientific innovations in research and development and clinical implementation and will involve acceptance by professional organizations. Indeed, implementation of this biology-informed framework will require stakeholder engagement at all stages to deliver precision diagnostic and treatments for mental disorders. Stakeholders include patients and patient-family organisations, representatives from broad research initiatives in psychiatric disorders (such as the FNIH led AMP® SCZ initiative [23]), professional organisations (such as the International College of Neuropsychopharmacology CINP, the American College of Neuropsychopharmacology ACNP, the European College of Neuropsychopharmacology ECNP, the European Psychiatric Association EPA, funders, representatives from industry (such as big pharma and small and medium-sized enterprises) and regulatory bodies, health care professionals and educators, among others.