¹University Doctoral Studies at "Carol Davila" University of Medicine and Pharmacy, Neuroscience, Bucharest, Romania

Background: Accumulating evidence indicates that immune dysregulation and low-grade systemic inflammation contribute to the pathophysiology, staging, and clinical heterogeneity of psychotic disorders. Hematologic inflammatory ratios and coagulation-related markers derived from routine laboratory testing represent accessible proxies of innate immune activation and thrombo-inflammatory processes. Recent studies suggest that inflammatory signatures may differ between acute psychotic states and chronic schizophrenia, supporting biologically informed stratification approaches.

Aims & Objectives: To compare peripheral inflammatory and hematologic markers between schizophrenia and acute and transient psychotic disorder, and to evaluate demographic and behavioral predictors of biomarker variability.

Method: 

This retrospective cohort study included 187 adult psychiatric inpatients admitted to a tertiary psychiatric hospital. Diagnoses were established according to ICD 10 criteria: schizophrenia (n = 105) and acute and transient psychotic disorder (n = 82). Exclusion criteria included significant medical comorbidity, substance use disorders, obesity (BMI > 30 kg/m²), pregnancy, acute infection, and heavy nicotine exposure. Laboratory parameters extracted at admission included total leukocyte count, neutrophils, lymphocytes, monocytes, platelets, C-reactive protein, erythrocyte sedimentation rate, and fibrinogen. Derived inflammatory indices included the neutrophil to lymphocyte ratio, the platelet to lymphocyte ratio, the monocyte to lymphocyte ratio, and the systemic immune-inflammatory index. Between-group comparisons were performed using parametric or Mann-Whitney U tests according to distribution. Multiple linear regression models examined the effects of age, sex, and smoking status.

Results: 

The acute psychosis group was younger than the schizophrenia group (40.06 ± 11.96 years vs 47.59 ± 10.07 years). Inflammatory ratios were significantly elevated in acute psychosis, indicating greater innate immune activation. Neutrophil to lymphocyte ratio was higher in acute psychosis (2.19 ± 1.04) compared with schizophrenia (1.79 ± 1.16; p = 0.004). Platelet-to-lymphocyte ratio was also increased (135.94 ± 40.81 vs 120.42 ± 80.51; p < 0.001), as was the monocyte-to-lymphocyte ratio (0.33±0.16 vs 0.31±0.33; p=0.03). The systemic immune-inflammatory index showed a similar pattern (587.12 ± 373.16 vs 452.14 ± 312.89; p = 0.004). In contrast, fibrinogen concentrations were significantly higher in schizophrenia (298.75 ± 51.17 mg/dL) compared with acute psychosis (269.29 ± 83.63 mg/dL; p = 0.02), suggesting a persistent proinflammatory and prothrombotic state. No significant differences were observed for total leukocyte count, neutrophils, monocytes, platelets, C-reactive protein, or erythrocyte sedimentation rate. Regression analyses indicated that sex significantly predicted platelet-to-lymphocyte ratio and fibrinogen levels, while smoking status predicted erythrocyte sedimentation rate, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio.

Parameter	Schizophrenia (n = 105) Mean ± SD	Acute psychosis (n = 82) Mean ± SD	p value
Neutrophil to lymphocyte ratio (NLR)	1.79 ± 1.16	2.19 ± 1.04	0.004
Platelet to lymphocyte ratio (PLR)	120.42 ± 80.51	135.94 ± 40.81	<0.001
Monocyte to lymphocyte ratio (MLR)	0.31 ± 0.33	0.33 ± 0.16	0.03
Systemic immune-inflammatory index (SII)	452.14 ± 312.89	587.12 ± 373.16	0.004
Fibrinogen (mg/dL)	298.75 ± 51.17	269.29 ± 83.63	0.02

Table 1. Significant inflammatory differences; values mean ± SD at admission; p < 0.05.

Discussion & Conclusions: Distinct inflammatory patterns support stage-related immune dysregulation across psychotic disorders. Elevated NLR, PLR, MLR, and SII in acute psychosis suggest intensified innate immune activation and stress-related inflammatory signaling during early phases. Higher fibrinogen in schizophrenia indicates a persistent thromboinflammatory state consistent with chronic illness burden and vascular risk. These findings align with neuroimmune models proposing dynamic immune involvement across illness stages and support the use of routine hematologic indices as accessible biomarkers for biological stratification and risk monitoring.