Benedetta Vai, Tommaso Cazzella, Camilla Monopoli, Beatrice Bravi, Anastasia Kontogianni, Celine Wessa, Courtney Worrell, Maria S Simon, Bernhard T Baune, Francesco Benedetti, Annamaria Cattaneo, Erik Van der Eycken, Jennifer C Felger, Stefan M Gold, Neil A Harrison, Nadia Hoffman, Femke Lamers, Marion Leboyer, Giulia Lombardo, Fanni-Laura Mäntylä, Andrew H Miller, Valeria Mondelli, Brenda W J H Penninx, Dan Stein, Luca Sforzini, Francesco Bavato, Michael Berk, Alessandra Borsini, Igor Branchi, Lucile Capuron, Javier R Caso, Janet L Cunningham, Paolo Fusar-Poli, Bartholomeus C M Haarman, Aiste Lengvenyte, Emanuele F Osimo, Christian Otte, Thomas A Pollak, Nils Eiel Steen, Carmine M Pariante, ASPIRE Study Consortium
These findings support a framework for ISMDD and highlight the importance of symptom assessment to improve clinical evaluation, research, and personalized immunopsychiatric treatment.
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.