A Delphi-method-based consensus for clinical domains and assessment of the inflammatory subtype of major depressive disorder from the ASPIRE study
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 first- and second-line antidepressants. However, a lack of consensus on its definition and assessment tools limits research and treatment development. Methods: Using a Delphi approach, international experts from the ASPIRE consortium (Advanced Stratification of People with Depression based on Inflammation, n = 25) identified ISMDD symptom domains, which were then evaluated by the European College of Neuropsychopharmacology Immuno-Neuropsychiatry Network (INPN-ECNP, n = 12). Using the same consensus structure, the coverage of these domains by depression rating scales was then assessed. People with lived experience (PWLE, n = 11) provided perspectives on the clinical relevance and impact of the emerged symptoms. Results: ASPIRE consensus identified ten ISMDD symptom domains: fatigue/low energy, hypersomnia, increased weight/appetite, cognitive difficulties, lack of motivation, anhedonia, diminished interest, leaden paralysis, psychomotor retardation, and insomnia, with the first five of being also confirmed by INPN-ECNP consensus. Except for increased weight/appetite, PWLE identified these domains as negatively affecting quality of life; most of them also reported as not sufficiently assessed in clinical care. Among rating scales, the Inventory of Depressive Symptomatology Self-Rated was the only instrument covering all ISMDD domains, whereas the Hamilton Depression Rating Scale and Montgomery-Asberg Depression Rating Scale covered only four and six domains, respectively. Conclusion: These findings support a framework for ISMDD and highlight the importance of symptom assessment to improve clinical evaluation, research, and personalized immunopsychiatric treatment.
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BibTeX
@article{vai2026delphimethodbased,
title = {{A Delphi-method-based consensus for clinical domains and assessment of the inflammatory subtype of major depressive disorder from the ASPIRE study}},
author = {Benedetta Vai and Tommaso Cazzella and Camilla Monopoli and Beatrice Bravi and Anastasia Kontogianni and Celine Wessa and Courtney Worrell and Maria Simon and Bernhard Baune and Francesco Benedetti and Annamaria Cattaneo and Erik Van Der Eycken and Jennifer Felger and Stefan Gold and Neil Harrison and Nadia Hoffman and Femke Lamers and Marion Leboyer and Giulia Lombardo and Fanni-Laura Mäntylä and Andrew Miller and Valeria Mondelli and Brenda W.J.H. Penninx and Dan Stein and Luca Sforzini and Francesco Bavato and Michael Berk and Alessandra Borsini and Igor Branchi and Lucile Capuron and Javier Caso and Janet Cunningham and Paolo Fusar-Poli and Bartholomeus C.M. Haarman and Aiste Lengvenyte and Emanuele Osimo and Christian Otte and Thomas Pollak and Nils Eiel Steen and Carmine Pariante and Livia De Picker},
journal = {Brain, Behavior, and Immunity},
year = {2026},
month = aug,
doi = {10.1016/j.bbi.2026.106957},
url = {https://hal.science/hal-05723195v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - A Delphi-method-based consensus for clinical domains and assessment of the inflammatory subtype of major depressive disorder from the ASPIRE study
AU - Benedetta Vai
AU - Tommaso Cazzella
AU - Camilla Monopoli
AU - Beatrice Bravi
AU - Anastasia Kontogianni
AU - Celine Wessa
AU - Courtney Worrell
AU - Maria Simon
AU - Bernhard Baune
AU - Francesco Benedetti
AU - Annamaria Cattaneo
AU - Erik Van Der Eycken
AU - Jennifer Felger
AU - Stefan Gold
AU - Neil Harrison
AU - Nadia Hoffman
AU - Femke Lamers
AU - Marion Leboyer
AU - Giulia Lombardo
AU - Fanni-Laura Mäntylä
AU - Andrew Miller
AU - Valeria Mondelli
AU - Brenda W.J.H. Penninx
AU - Dan Stein
AU - Luca Sforzini
AU - Francesco Bavato
AU - Michael Berk
AU - Alessandra Borsini
AU - Igor Branchi
AU - Lucile Capuron
AU - Javier Caso
AU - Janet Cunningham
AU - Paolo Fusar-Poli
AU - Bartholomeus C.M. Haarman
AU - Aiste Lengvenyte
AU - Emanuele Osimo
AU - Christian Otte
AU - Thomas Pollak
AU - Nils Eiel Steen
AU - Carmine Pariante
AU - Livia De Picker
PY - 2026
DA - 2026/08/16
JO - Brain, Behavior, and Immunity
DO - 10.1016/j.bbi.2026.106957
UR - https://hal.science/hal-05723195v1
AB - 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 first- and second-line antidepressants. However, a lack of consensus on its definition and assessment tools limits research and treatment development. Methods: Using a Delphi approach, international experts from the ASPIRE consortium (Advanced Stratification of People with Depression based on Inflammation, n = 25) identified ISMDD symptom domains, which were then evaluated by the European College of Neuropsychopharmacology Immuno-Neuropsychiatry Network (INPN-ECNP, n = 12). Using the same consensus structure, the coverage of these domains by depression rating scales was then assessed. People with lived experience (PWLE, n = 11) provided perspectives on the clinical relevance and impact of the emerged symptoms. Results: ASPIRE consensus identified ten ISMDD symptom domains: fatigue/low energy, hypersomnia, increased weight/appetite, cognitive difficulties, lack of motivation, anhedonia, diminished interest, leaden paralysis, psychomotor retardation, and insomnia, with the first five of being also confirmed by INPN-ECNP consensus. Except for increased weight/appetite, PWLE identified these domains as negatively affecting quality of life; most of them also reported as not sufficiently assessed in clinical care. Among rating scales, the Inventory of Depressive Symptomatology Self-Rated was the only instrument covering all ISMDD domains, whereas the Hamilton Depression Rating Scale and Montgomery-Asberg Depression Rating Scale covered only four and six domains, respectively. Conclusion: These findings support a framework for ISMDD and highlight the importance of symptom assessment to improve clinical evaluation, research, and personalized immunopsychiatric treatment.
SN - 0889-1591
SN - 1090-2139
ER -