Peer-Reviewed Publication
Brain Behav Immun2026;106957.August 16, 2026Journal Article
A Delphi-method-based consensus for clinical domains and assessment of the inflammatory subtype of major depressive disorder from the ASPIRE study.
Benedetta Vai1, Tommaso Cazzella2, Camilla Monopoli3, Beatrice Bravi4, Anastasia Kontogianni5, Celine Wessa5, Courtney Worrell6, Maria S Simon7, Bernhard T Baune8, Francesco Benedetti2, Annamaria Cattaneo9, Erik Van der Eycken10, Jennifer C Felger11, Stefan M Gold12, Neil A Harrison13, Nadia Hoffman14, Femke Lamers15, Marion Leboyer16, Giulia Lombardo6, Fanni-Laura Mäntylä10, Andrew H Miller11, Valeria Mondelli17, Brenda W J H Penninx15, Dan Stein14, Luca Sforzini17, Francesco Bavato18, Michael Berk19, Alessandra Borsini6, Igor Branchi20, Lucile Capuron21, Javier R Caso22, Janet L Cunningham23, Paolo Fusar-Poli24, Bartholomeus C M Haarman25, Aiste Lengvenyte26, Emanuele F Osimo27, Christian Otte28, Thomas A Pollak29, Nils Eiel Steen30, Carmine M Pariante17,
1Psychiatry and Clinical Psychobiology Unit, Division of Neuroscience, IRCCS Ospedale San Raffaele, Milano, Italy; University Vita-Salute San Raffaele, Milano, Italy. Electronic address: vai.benedetta@hsr.it.
2Psychiatry and Clinical Psychobiology Unit, Division of Neuroscience, IRCCS Ospedale San Raffaele, Milano, Italy; University Vita-Salute San Raffaele, Milano, Italy.
3Psychiatry and Clinical Psychobiology Unit, Division of Neuroscience, IRCCS Ospedale San Raffaele, Milano, Italy.
4University Vita-Salute San Raffaele, Milano, Italy.
5University Psychiatric Hospital Campus Duffel, Duffel, Belgium; Collaborative Antwerp Psychiatric Research Institute, Faculty of Health Sciences, University of Antwerp, Antwerp, Belgium.
6Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London SE5 9RT, UK.
7Department of Psychiatry and Psychotherapy, University Hospital, Ludwig-Maximilian-University, Munich, Germany.
8Department of Psychiatry, University of Münster, Münster, Germany; Department of Psychiatry, University of Melbourne, Melbourne, Australia; Department of Psychiatry, University of Western Australia, Perth, Australia.
9Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy; Biological Psychiatry Unit, IRCCS Istituto Centro San Giovanni di Dio, Fatebenefratelli, Brescia, Italy.
10Global Alliance of Mental Illness Advocacy Networks-Europe, Brussels, Belgium.
11Department of Psychiatry and Behavioural Sciences, Emory University School of Medicine, Atlanta, GA, USA.
12Department of Psychiatry and Medical Department, Section Psychosomatic Medicine, Campus Benjamin Franklin, Charité- Universitätsmedizin Berlin, Berlin, Germany; German Center for Mental Health (DZPG), Partner Site Berlin-Potsdam, Berlin, Germany.
13Division of Psychological Medicine and Clinical Neuroscience, Department of Medicine, Cardiff University, Cardiff, UK.
14Neuroscience Institute, University of Cape Town, Cape Town, South Africa; Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa.
15Department of Psychiatry, Amsterdam UMC, Vrije Universiteit, Amsterdam, Netherlands; Amsterdam Public Health, Mental Health Program, Amsterdam UMC, Amsterdam, Netherlands.
16Fondation FondaMental, Créteil, France; Universite Paris-Est Creteil (UPEC), INSERM U955, IMRB, Translational Neuro-psychiatry laboratory, Programme Français en Psychiatrie de Precision (PEPR PROPSY), Departement Medico-Universitaire de Psychiatrie et d'Addictologie des Hopitaux Henri Mondor (AP-HP), Creteil F-94010, France.
17Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London SE5 9RT, UK; National Institute for Health and Care Research (NIHR) Maudsley Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London, UK.
18Department of Adult Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Zurich, Switzerland; Center of Functionally Integrative Neuroscience, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
19IMPACT - the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Geelong, VIC, Australia Barwon Health University Hospital, Geelong, Australia.
20Center for Behavioral Sciences and Mental Health, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy.
21Univ. Bordeaux, INRAE, Bordeaux INP, NutriNeuro, UMR 1286, F-33000 Bordeaux, France.
22Department of Pharmacology and Toxicology, School of Medicine, and University Institute for Research in Neurochemistry (IUIN), Universidad Complutense de Madrid, Madrid, Spain; Centro de Investigación Biomédica en Red de Salud Mental, Instituto de Salud Carlos III (CIBERSAM, ISCIII), Madrid, Spain.
23Department of Medical Sciences, Clinical Psychiatry, Uppsala University, Uppsala Sweden.
24Early Psychosis: Interventions and Clinical-detection (EPIC) Lab, Department of Psychosis Studies, King's College London, UK; Department of Brain and Behavioral Sciences, University of Pavia, Italy; Outreach and Support in South-London (OASIS) Service, South London and Maudlsey (SLaM) NHS Foundation Trust, UK.
25Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
26Department of Emergency Psychiatry and Acute Care, Lapeyronie Hospital, CHU Montpellier, Montpellier, France; IGF, University of Montpellier, CNRS, INSERM, Montpellier, France.
27Department of Psychiatry, University of Cambridge, Cambridge, UK; Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, UK; Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK; South London and Maudsley NHS Foundation Trust, London, UK.
28German Center for Mental Health (DZPG), Partner Site Berlin-Potsdam, Berlin, Germany; Department of Psychiatry and Neurosciences, Campus Benjamin Franklin, Charité- Universitätsmedizin Berlin, Berlin, Germany.
29Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK; South London and the Maudsley NHS Foundation Trust, London, UK.
30Division of Mental Health and Addiction, Oslo University Hospital, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Division of Mental Health and Substance Abuse, Diakonhjemmet Hospital, Oslo, Norway.
Abstract
BACKGROUND: Elevated inflammatory biomarkers have been consistently associated with a subset of depressive symptoms, particularly atypical and energy-related features, as well as antidepressant treatment resistance. This evidence has supported the definition of an inflammatory subtype of major depressive disorder (ISMDD), characterized by immune-inflammatory dysregulation and reduced response to f…
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