What question did this study set out to answer?

This study aims to identify a cytokine-lncRNA signature that distinguishes schizophrenia patients with negative symptoms from healthy controls.

January 25, 2026Open Access

A Dual-Marker Peripheral Signature of IL-6 Elevation and NEAT1 Reduction in Negative-Symptom Schizophrenia: A Cross-Sectional Study

Key Points

This study aims to identify a cytokine-lncRNA signature that distinguishes schizophrenia patients with negative symptoms from healthy controls.
Participants included 41 hospitalized schizophrenia patients and 20 healthy controls, matched by age and sex.
Negative symptom subgroups were defined using two Brief Negative Symptom Scale criteria.
Serum levels of IL-6, TNF-α, IL-10, and lncRNAs (NEAT1, MALAT1, MEG3) were measured using enzyme-linked immunosorbent assay and quantitative RT-PCR.
Logistic and multinomial models were used to assess discriminative power, adjusting for potential confounders.
IL-6 levels significantly correlated with PANSS Total and Negative scores, showing elevated levels in schizophrenia patients compared to controls.
NEAT1 was significantly reduced in negative-symptom subgroups based on BNSS criteria.
The dual-marker pattern of increased IL-6 and decreased NEAT1 provided strong discrimination for identifying severe symptoms in schizophrenia, with an AUC of 0.85.

Abstract

Abstract Background: Schizophrenia (SCZ) shows marked biological heterogeneity, with negative symptoms linked to poor outcomes and hypothesized immune dysregulation. This study examined whether a peripheral cytokine–long non-coding RNA (lncRNA) panel could distinguish patients with SCZ and Brief Negative Symptom Scale (BNSS) -defined subgroups from healthy controls (HC). Methods: Forty-one hospitalized patients with SCZ completed the BNSS and the Positive and Negative Syndrome Scale (PANSS). Twenty HCs, frequency-matched for age and sex, served as comparison samples. Severe negative-symptom subgroups were defined using two BNSS criteria: a broader (SNS1) and a more restrictive (SNS2) threshold. Serum cytokines—interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10) —and leukocyte lncRNAs (MALAT1, NEAT1, MEG3) were quantified by enzyme-linked immunosorbent assay and quantitative RT-PCR. Covariate-adjusted logistic and multinomial models (adjusting for age, sex, body mass index, and smoking) assessed discrimination using area under the receiver-operating-characteristic curve (AUC) and interquartile-range odds ratios (ORIQR). Results: IL-6 correlated with PANSS Total (ρ =. 48, p =. 001) and Negative (ρ =. 34, p =. 032) scores and was higher in SCZ than HC (p =. 033), with further increases in SNS subgroups. NEAT1 was significantly reduced only within BNSS-defined subgroups (p ≤. 025). The dual-marker pattern (IL-6 ↑, NEAT1 ↓) showed the strongest discrimination for SNS1 versus HC (AUC = 0. 85) and the steepest multinomial contrasts for SNS2 (IL-6 ORIQR = 4. 98; NEAT1 ORIQR = 0. 11). Conclusions: Elevated IL-6 and decreased NEAT1 define a peripheral signature linked to negative-symptom severity in SCZ and may support biologically informed stratification and longitudinal research.

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Cite This Study

Moga et al. (Fri,) studied this question.

synapsesocial.com/papers/6975b229feba4585c2d6db02 https://doi.org/https://doi.org/10.1017/neu.2026.10055

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