2026 ECNP Congress

PS03-3244

Developing a core outcome set for negative symptoms of schizophrenia: the SNAP project protocol

Silvia Zaragoza Domingo — M. Martinez-Cengotitabengoa, M. Avila · Neurospychological Research Organization s.l, Neuropsynchro, Barcelona, Spain

2026 ECNP Congress

Background

Negative symptoms of schizophrenia—avolition, anhedonia, asociality, blunted affect, and alogia—represent a major unmet need in psychiatry. They cluster into two dimensions: diminished motivation and pleasure (MAP) and diminished expression (EXP) [1], both strongly linked to impaired social and occupational functioning and reduced quality of life. Qualitative describe emotional numbness, loss of goal-directed behaviour, and social isolation [2]. Progress in treatment development remains limited by heterogeneous outcome measurement, underscoring the need for a standardised Core Outcome Set (COS).

Objectives

As part of the ECNP educational program, the Schizophrenia Negative Assessment Protocol (SNAP) project aims to develop a research protocol for identifying a COS suitable for phase 2 and 3 randomised controlled trials of pharmacological treatments targeting negative symptoms in adults with chronic or stable-phase schizophrenia. Objectives are to: (a) map relevant outcome domains from the existing evidence base and stakeholder input; (b) systematically evaluate candidate outcome measurement instruments (OMIs); and (c) achieve formal multistakeholder consensus on a minimum set of domains and instruments appropriate for regulatory-grade efficacy assessment.

Methods

The SNAP protocol follows the 7-step ECNP COA Group framework (v3.0), aligned with COMET/COS-STAD methodology [3]. Steps include disease modelling and literature review; scope definition and context of use; multistakeholder involvement; identification of outcome domains via qualitative synthesis and conceptual disease impact modelling; systematic evaluation of OMIs; consensus recommendations; and gap analysis. Consensus will be achieved through a multi-round Delphi survey (9-point importance scale, ≥70% agreement) involving 70–90 international stakeholders. OMIs will be evaluated using COSMIN criteria, incorporating both clinician-and patient- reported outcomes under Neuroscience-based Nomenclature (NBN) conventions.

Preliminary results from targeted literature review (Step 1 and Step 5)

A qualitative scoping review [2] identified key experiential themes, including loss of motivation, social withdrawal, and altered narrative identity, informing a conceptual disease impact model. First-generation clinician-rated scales showed broad coverage but limited sensitivity to experiential MAP deficits. Second-generation instruments demonstrated stronger psychometric performance, with excellent inter-rater reliability for the Brief Negative Symptom Scale (BNSS) (ICC ≥0.90), and good construct validity for the Clinical Assessment Interview Negative Symptoms (CAINS) [4]. Patient-reported measured captured extended subjective experiences, while blood-based biomarkers (brain-derived neurotrophic factor (BDNF), inflammatory cytokines, and circulating microRNAs) emerged as promising exploratory correlates [5]. (Table 1).

Table 1. Recommended outcome measurement instruments and biomarkers for the SNAP COS

Instrument Domains covered Type (NBN) Endpoint role Reporter
Instrument Domains covered Type (NBN) Endpoint role Reporter
BNSS All 5 core domains: avolition, anhedonia, asociality, blunted affect, alogia ClinRO Primary Clinician
CAINS All 5 core domains; emphasis on MAP ClinRO Primary / secondary Clinician
SNS All 5 domains (self-perceived) PRO Supplementary Patient
MAP-SR MAP domains PRO Supplementary Patient
Blood-based biomarkers (BDNF, cytokines, miRNA) Biological correlates Biological Exploratory Laboratory

Conclusions

The SNAP protocol provides a patient-centred, multistakeholder framework for COS development in schizophrenia negative symptoms, aligned with ECNP, COMET, and regulatory standards. Integrating second-generation clinician-rated instruments, validated patient-reported measures, and exploratory biomarkers ensures coverage of both MAP and EXP dimensions. Finalisation through Delphi consensus, and early regulatory engagement will support a standardised, evidence-based endpoint strategy for future phase 3 trials.

References

  1. Marder SR, Galderisi S. The current conceptualization of negative symptoms in schizophrenia. World psychiatry. 2017 Feb;16(1):14-24.
  2. Lyne J, Piacenza F, Crowley P, Smyth J, O’Donoghue B, Gaynor K, Clarke M. Negative symptoms in psychosis: A scoping review of qualitative studies. Schizophrenia research. 2025 May 1;279:40-9.
  3. Galderisi S, Mucci A, Dollfus S, Nordentoft M, Falkai P, Kaiser S, Giordano GM, Vandevelde A, Nielsen MØ, Glenthøj LB, Sabé M. EPA guidance on assessment of negative symptoms in schizophrenia. European Psychiatry. 2021 Jan;64(1):e23.
  4. Kirkpatrick B, Strauss GP, Nguyen L, Fischer BA, Daniel DG, Cienfuegos A, Marder SR. The brief negative symptom scale: psychometric properties. Schizophrenia bulletin. 2011 Mar 1;37(2):300-5.
  5. Martínez-Cengotitabengoa M, MacDowell KS, Alberich S, Diaz FJ, García-Bueno B, Rodriguez-Jimenez R, Bioque M, Berrocoso E, Parellada M, Lobo A, Saiz PA. BDNF and NGF signalling in early phases of psychosis: relationship with inflammation and response to antipsychotics after 1 year. Schizophrenia bulletin. 2016 Jan 1;42(1):142-51.