Vai, Benedetta, Cazzella, Tommaso, Monopoli, Camilla, Bravi, Beatrice, Kontogianni, Anastasia and Harrison, Neil A.  ORCID: https://orcid.org/0000-0002-9584-3769
2026.
A Delphi-method-based consensus for clinical domains and assessment of the inflammatory subtype of major depressive disorder from the ASPIRE study.
Brain, Behavior, and Immunity
138
, 106957.
10.1016/j.bbi.2026.106957
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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.
| Item Type: | Article |
|---|---|
| Date Type: | Publication |
| Status: | Published |
| Schools: | Schools > Medicine |
| Additional Information: | For full author list see https://doi.org/10.1016/j.bbi.2026.106957 |
| Publisher: | Elsevier |
| ISSN: | 0889-1591 |
| Date of First Compliant Deposit: | 24 August 2026 |
| Date of Acceptance: | 13 August 2026 |
| Last Modified: | 06 Oct 2026 10:02 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/189132 |
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