Clinical and Inflammatory Correlates of Negative Symptom Dimensions in Schizophrenia: Cross-Sectional Evidence for Neutrophil-to-Lymphocyte Ratio Associations With Motivational Deficits in Hospitalized Patients

TL;DR

This study found that the neutrophil-to-lymphocyte ratio is linked to motivational deficits in hospitalized schizophrenia patients.

Contribution

The study identifies NLR as a novel biological correlate of motivational negative symptoms in schizophrenia.

Findings

NLR was significantly associated with asociality and motivational deficits in schizophrenia patients.

CRP showed a weak link to avolition, particularly in non-overweight patients.

C4 had no significant association with any negative symptom domain.

Abstract

Background: This study examined negative symptom dimensions and their biological correlates in patients with schizophrenia under routine hospital conditions.

Objective: To assess whether demographic, clinical, and inflammatory markers, that is, C-reactive protein (CRP), complement component 4 (C4), and the neutrophil-to-lymphocyte ratio (NLR), contribute to variation across negative symptom domains measured using two complementary instruments.

Methodology: A cross-sectional study was conducted at the Clinics I-II of Psychiatry, Cluj-Napoca, Romania (May-September 2023). Forty-five inpatients with schizophrenia were evaluated using the Brief Negative Symptom Scale (BNSS) and the Positive and Negative Syndrome Scale (PANSS). Fasting CRP and C4 were measured, and NLR was calculated from differential blood counts. Analyses included descriptive statistics, Shapiro-Wilk testing, parametric/nonparametric comparisons, and Pearson/Spearman correlations. Multiple linear regressions included biomarkers as predictors and were adjusted for sex, age, body mass index (BMI), smoking, chlorpromazine-equivalent dose, and clozapine treatment; models were compared using Akaike Information Criterion (AIC) (ΔAIC ≤ 2). Sensitivity analyses excluded clozapine-treated patients and additionally adjusted for PANSS Positive and General Psychopathology totals.

Results: BMI correlated negatively with negative symptoms (PANSS negative: ρ = −.43) and positively with CRP (ρ = .67). Stratified analyses revealed a CRP-Avolition association in non-overweight patients (ρ = .49) and stronger neutrophil-to-lymphocyte ratio (NLR)-motivational domain correlations in clozapine-treated patients (Asociality/Motivation and Pleasure (MAP): ρ = .59-.66). In covariate-adjusted, AIC-selected models, NLR remained significant for Asociality, PANSS Emotional Withdrawal, and MAP (adjusted R² = .19-.24; partial R² = .10-.16). CRP was retained only for Avolition with limited explained variance (adjusted R² = .03; partial R² = .09). C4 did not enter any final model.

Conclusion: In this inpatient cohort, NLR was the most consistent correlate of motivational negative symptoms, while CRP showed a weak association with Avolition, and C4 showed no clear relationship. Findings are hypothesis-generating and require replication in larger, longitudinal samples.

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