Advancing precision psychiatry and targeted treatments: Insights from immunopsychiatry

Andrew H Miller; Michael Berk; Gilles Bloch; Veronique Briquet-Laugier; Carinne Brouillon; Bruce N Cuthbert; Robert Dantzer; Michael C Davis; Livia J De Picker; Wayne C Drevets; Harris A Eyre; Laura M Hack; Neil A Harrison; Andrew D Krystal; Giulia Lombardo; Valeria Mondelli; Carmine M Pariante; Luigi Pulvirenti; Giacomo Salvadore; Luca Sforzini; Pawel Swieboda; Madhukar H Trivedi; Marion Leboyer

doi:10.1016/j.bbi.2025.01.002

Advancing precision psychiatry and targeted treatments: Insights from immunopsychiatry

Brain Behav Immun. 2025 Jan 17:125:319-329. doi: 10.1016/j.bbi.2025.01.002. Online ahead of print.

Authors

Andrew H Miller¹, Michael Berk², Gilles Bloch³, Veronique Briquet-Laugier⁴, Carinne Brouillon⁵, Bruce N Cuthbert⁶, Robert Dantzer⁷, Michael C Davis⁸, Livia J De Picker⁹, Wayne C Drevets¹⁰, Harris A Eyre¹¹, Laura M Hack¹², Neil A Harrison¹³, Andrew D Krystal¹⁴, Giulia Lombardo¹⁵, Valeria Mondelli¹⁵, Carmine M Pariante¹⁶, Luigi Pulvirenti¹⁷, Giacomo Salvadore¹⁸, Luca Sforzini¹⁵, Pawel Swieboda¹⁹, Madhukar H Trivedi²⁰, Marion Leboyer²¹

Affiliations

¹ Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA. Electronic address: [email protected].
² Institute for Mental and Physical Health and Clinical Translation (IMPACT), School of Medicine and Barwon Health, Deakin University, Geelong, VIC 3220, Australia.
³ National Museum of Natural History of France, Paris, France.
⁴ Fondation FondaMental, Créteil, France.
⁵ BMD Human Pharma C.H. Boehringer Sohn AG & Co, KG Binger Str. 173 55216, Ingelheim am Rhein, Germany.
⁶ National Institute of Mental Health, Bethesda, MD, USA.
⁷ Department of Symptom Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁸ Usona Institute, Fitchburg, WI, USA.
⁹ Collaborative Antwerp Psychiatric Research Institute, University of Antwerp, Antwerp, Belgium.
¹⁰ Janssen Research & Development, LLC, of Johnson & Johnson, San Diego, CA, USA.
¹¹ Neuro-Policy Program, Center for Health and Biosciences, The Baker Institute for Public Policy, Rice University, Houston, TX, USA.
¹² Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA.
¹³ Division of Psychological Medicine and Clinical Neuroscience, Cardiff University, Cardiff, UK.
¹⁴ Department of Psychiatry, University of California, San Franscisco Weill Institute for Neurosciences, San Francisco, CA, USA.
¹⁵ Institute of Psychiatry, Psychology and Neuroscience, Department of Psychological Medicine, Maurice Wohl Clinical Neuroscience Institute, King's College London, UK.
¹⁶ Institute of Psychiatry, Psychology and Neuroscience, Maurice Wohl Clinical Neuroscience Institute, King's College London, UK.
¹⁷ Neuroscience School of Advanced Studies, London, UK.
¹⁸ Clinical Development, Alector, Bethesda, MD, USA.
¹⁹ NeuroCentury, Brussels, Belgium.
²⁰ Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA.
²¹ Univ Paris Est Créteil, INSERM U955, IMRB, Translational NeuroPsychiatry Laboratory, Fondation FondaMental, Créteil, France.

PMID: 39828008
DOI: 10.1016/j.bbi.2025.01.002

Abstract

Despite tremendous advancements in neuroscience, there has been limited impact on patient care. Current psychiatric treatments are largely non-specific, and drug development is hindered by outdated, overinclusive diagnostic categories and a "one-size-fits-all" approach. Additionally, mechanisms underlying psychiatric illnesses and their treatments with conventional medications remain poorly understood. Precision psychiatry is a strategy that holds great promise for novel therapies targeting specific pathophysiologic mechanisms in selected patients, ultimately contributing to more effective, personalized treatments. Immunopsychiatry, which focuses on the immune system's role in psychiatric disorders, exemplifies the challenges and potential solutions for precision psychiatry. Despite understanding how inflammation contributes to psychiatric illness, results of clinical trials with anti-inflammatory drugs have been inconsistent and underwhelming. Shortcomings of these trials include a lack of focus on subgroups of patients with increased inflammation, the use of non-specific outcome variables (e.g., not specific to inflammation's impact on the brain and behavior), and failure to establish target engagement of the inflammatory response. To advance anti-inflammatory treatments, clinical trials should: 1) enrich for patients using predictive biomarkers; 2) use clinical outcome assessments that align with inflammation's effects on the brain; 3) consider novel diagnostic constructs linked to inflammation; and 4) verify target engagement. Moreover, greater attention should be paid to efforts to repurpose available anti-inflammatory drugs while awaiting development of novel treatments targeting more specific immune pathways. Taken together, a collaborative approach involving academia, industry, funding agencies, patients, payors, and policymakers is required to advance Immunopsychiatry and ultimately provide a roadmap for successful implementation of precision psychiatry.

Keywords: Anti-inflammatory drugs; Biomarkers; Clinical Outcome Assessments; Clinical Trials; Depression; Drug development; Immunopsychiatry; Inflammation; Personalized Medicine; Psychiatry.

Publication types

Review