2026 ECNP Congress

PS01-1088

From peripheral inflammation to CNS injury: composite indices capture neuropsychiatric burden in stable autoimmune disease

María Recio-Barbero — I. Horrillo, G. Ruiz-Irastorza, S. Arostegui, I. Querejeta, R. Pérez-Garay, J. Cabezas-Garduño, J.J. Meana, R. Segarra · Biobizkaia Health Research Institute, Early Stages of Pychosis Group. Psychiatry Department. Cruces University Hospital, Barakaldo, Spain

2026 ECNP Congress

Background

Systemic lupus erythematosus (SLE) carries a high burden of neuropsychiatric comorbidity, with major depressive disorder emerging as one of its most prevalent and disabling manifestations [1], although its biological underpinnings and shared neuro-immune substrate remain poorly characterized [2,3]. Composite haematological inflammatory indices, including the Systemic Immune-Inflammation Index (SII) and the Systemic Inflammation Response Index (SIRI), have recently emerged as accessible and reproducible biomarkers of neuropsychiatric burden in primary psychiatric and neurological conditions [4], yet their utility in immune-mediated disease with concomitant psychiatric comorbidity has not been formally established [5]. The present study examines whether SII and SIRI capture a distinct neuroinflammatory phenotype in SLE-MDD, even in clinically stable patients with low disease activity and low accumulated organ damage.

Methods

This multicenter cross-sectional study included a total of 154 participants distributed across four diagnostic groups: SLE without psychiatric comorbidity (n=77), SLE with comorbid major depression (SLE-MDD; n=15), Major Depressive Disorder (MDD) (n=27), and age-matched healthy controls (n=35). Composite inflammatory indices (NLR, MLR, PLR, SII and SIRI) were calculated from routine peripheral blood counts. Psychiatric assessment included the Montgomery-Åsberg Depression Rating Scale (MADRS), the Hamilton Anxiety Rating Scale (HARS), and the Plutchik Suicide Risk Scale. CNS injury markers (S100B, NSE) and circulating cytokines (IL-6, IFN-γ, IL-10) were quantified by ELISA. Between-group differences were assessed by Kruskal-Wallis tests with Dunn’s post-hoc correction, and bivariate associations were evaluated using Spearman correlations.

Results

Despite clinically stable disease (low SLEDAI-2K), low accumulated organ damage (SDI) and low-dose glucocorticoid maintenance therapy (median 2.5 mg/day), both SII and SIRI were significantly elevated in the SLE-MDD group compared with SLE, primary MDD, and healthy controls. Both indices correlated with depressive symptom severity (SII: ρ=0.182; SIRI: ρ=0.212), anxiety severity on the HARS (SII: ρ=0.229), and suicidal risk assessed by the Plutchik Suicide Risk Scale (SII: ρ=0.335; SIRI: ρ=0.314), thereby linking systemic innate immune activation to the full neuropsychiatric symptom spectrum. The SIRI index also correlated with CRP (ρ=0.251), further supporting its role as a marker of innate immune activation. The PLR showed the strongest association with IFN-γ (ρ=0.350), while the NLR specifically differentiated SLE-MDD from primary MDD patients. S100B was elevated across all patient groups versus controls, indicating diffuse glial involvement regardless of diagnostic category, whereas NSE was decreased across all patient groups compared with controls, a pattern consistent with chronic rather than acute CNS injury.

Conclusions

SII and SIRI identify a distinct neuroinflammatory phenotype in SLE-MDD that is independent of clinical disease activity and accumulated organ damage, and that extends across depressive, anxious and suicidal risk dimensions. These accessible composite biomarkers, derived directly from routine peripheral blood counts, may represent a feasible translational tool for early neuropsychiatric risk stratification in patients with immune-mediated diseases, warranting prospective validation in larger and longitudinal cohorts to confirm their clinical utility.

References

  1. Moustafa AT, Moazzami M, Engel L, Bangert E, Hassanein M, Marzouk S, et al. Prevalence and metric of depression and anxiety in systemic lupus erythematosus: a systematic review and meta-analysis. Semin Arthritis Rheum. 2020;50(1):84-94.
  2. Miller AH, Raison CL. The role of inflammation in depression: from evolutionary imperative to modern treatment target. Nat Rev Immunol. 2016;16(1):22-34.
  3. Magro-Checa C, Zirkzee EJ, Huizinga TW, Steup-Beekman GM. Laboratory and neuroimaging biomarkers in neuropsychiatric systemic lupus erythematosus: where do we stand, where to go? Front Med (Lausanne). 2018;5:340.
  4. Mazza MG, De Lorenzo R, Conte C, Poletti S, Vai B, Bollettini I, et al. Anxiety and depression in COVID-19 survivors: role of inflammatory and clinical predictors. Brain Behav Immun. 2020;89:594-600.
  5. Yang CH, Wang XY, Zhang YH, Ding N. SIRI and SII as potential biomarkers of disease activity and lupus nephritis in systemic lupus erythematosus. Front Immunol. 2025;16:1530534.