2026 ECNP Congress

PS04-4226

Peripheral inflammatory indices versus clinical and cognitive predictors of one-year functional outcome in first-episode psychosis

Rodrigo Romero-Jimenez — M. Recio-Barbero, I. Horrillo, O. Mentxaka, J. Cabezas-Garduño, E. Collado-González, L. Urigüen, L.F. Callado, P. Unzueta-Larrinaga, R. Segarra · Biobizkaia Health Research Institute - Cruces University Hospital, Early Stages of Psychosis Group - Psychiatry Department, Barakaldo- Bizkaia, Spain

2026 ECNP Congress

Background

Identifying baseline predictors of long-term functional outcome after a first-episode psychosis (FEP) is a clinical priority, particularly when these include accessible markers obtainable from a routine blood draw. Beyond classical predictors such as duration of untreated psychosis (DUP) and baseline cognition [1,2], composite haematological inflammatory indices, including neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic inflammation response index (SIRI) and systemic immune-inflammation index (SII), have been proposed as accessible read-outs of immune dysregulation in psychosis [3,4]. Whether these markers add prognostic value to clinical and cognitive predictors of functional evolution after a FEP, including affective and non-affective presentations, is largely unexplored.

Aims

To identify which baseline variables (sociodemographic, clinical, cognitive and inflammatory) are independently associated with one-year functional outcome in a real-world FEP cohort, using an integrative model.

Methods

Prospective register-based cohort of 50 adults consecutively admitted for a first psychotic episode (45 non-affective, 4 affective; 53% female; mean age 35±12 years; median DUP 1 month). One participant with biochemical evidence of acute infection was excluded a priori, leaving 49 analysable cases. At admission we collected sociodemographic data, the Positive and Negative Syndrome Scale (PANSS), complete blood count and C-reactive protein (CRP), and computed NLR, MLR, PLR, SIRI and SII directly on raw counts (×10⁹/L). Cognition was rated with the Brief Assessment of Cognition in Schizophrenia (BACS) using age- and sex-corrected T-scores. Functioning was rated with the Global Assessment of Functioning (GAF) at admission and at 12 months. Univariate associations with 12-month GAF were screened with Spearman correlations. A multivariable linear regression integrated the strongest clinical, cognitive and inflammatory candidates without diagnostic-group adjustment (α=0.05).

Results

Mean baseline PANSS total score was 103.6±33.2 and GAF basal score 48.6±11.6. At 12 months GAF reached 74.4±14.0 (mean change +25.8±15.9); 68.8% achieved a GAF ≥70 and 8.2% were readmitted. In univariate analyses, longer DUP was the only robust predictor of poorer 12-month GAF (rho=−0.45, p=0.002); age, sex, baseline PANSS, individual blood counts, CRP and all five inflammatory ratios showed no significant correlation (all rho≤0.18, p>0.20). Cross-sectionally, however, higher PLR and SII were inversely correlated with PANSS-Positive scores (rho=−0.36, p=0.01 and rho=−0.31, p=0.03), in line with recent reports suggesting a potentially protective role of platelet-related indices in psychosis [5]. In the integrative multivariable model (R²=0.35, n=45), DUP remained the only independent predictor of 12-month GAF (β=−0.43, 95% CI −0.71 to −0.15, p=0.003), with BACS composite showing a positive trend (β=+0.35, p=0.064); baseline GAF, PANSS-Total, age and sex were non-significant. Adding each inflammatory ratio individually did not improve model fit (all p>0.40).

Conclusions

In this FEP cohort, DUP was the dominant predictor of one-year functional outcome, with global cognition showing a positive trend. Inflammatory ratios showed a plausible cross-sectional inverse association between platelet-related indices and positive symptoms, but did not predict functional evolution beyond clinical and cognitive variables. DUP and baseline cognition emerge as the most consistent early predictors of one-year functioning, whereas the prognostic value of inflammatory ratios may require larger samples and dynamic immune assessments to be robustly established.

References

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  2. Cowman M, Holleran L, Lonergan E, et al. Cognitive predictors of social and occupational functioning in early psychosis: a systematic review and meta-analysis of cross-sectional and longitudinal data. Schizophr Bull. 2021;47:1243–1253.
  3. Mazza MG, Lucchi S, Rossetti A, Clerici M. Neutrophil-lymphocyte ratio, monocyte-lymphocyte ratio and platelet–lymphocyte ratio in non-affective psychosis: a meta-analysis and systematic review. World J Biol Psychiatry. 2020;21:326–338.
  4. Llorca-Bofí V, Bioque M, Pàmpols-Pérez S, et al. Blood-based immune biomarkers and functional outcomes in acute schizophrenia: a retrospective cohort study. Spanish Journal of Psychiatry and Mental Health. 2026;Mar 21:S2950-2853(26)00018-9.
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