2026 ECNP Congress

PS01-1210

Peripheral immune inflammation in schizophrenia: group-level elevation with limited diagnostic separation – a case-control study

Andrei Gabriel Zanfir — S. Trifu · Carol Davila University of Medicine and Pharmacy, Neuroscience, Bucharest, Romania

2026 ECNP Congress

Background

Peripheral immune dysregulation is increasingly discussed as a biologically relevant dimension of schizophrenia, although its clinical meaning remains non-specific [1]. Complete blood count-derived inflammatory indices offer a pragmatic way of translating immune variation into measurable parameters and have been associated with symptom dimensions and cognitive deficits in schizophrenia [2]. The systemic immune-inflammation index, calculated as platelet count multiplied by neutrophil count and divided by lymphocyte count, combines platelet, neutrophil, and lymphocyte counts into a composite peripheral inflammatory marker; recent studies have examined its relevance across schizophrenia and other major psychiatric disorders, across illness stages, and in relation to cognitive impairment [3, 4, 5]. However, the distinction between group-level inflammatory differences and individual-level diagnostic utility remains clinically important.

Aims

This case-control study examined whether adults with clinician-confirmed DSM-5 schizophrenia show higher systemic immune-inflammation index values than demographically matched primary-care controls.

Methods

A case-control design was used. The clinical group included 124 adults aged 18-65 years with clinician-confirmed DSM-5 schizophrenia. All were receiving antipsychotic treatment; clozapine was excluded because of its distinct haematological and inflammatory profile. The control group included 128 adults recruited from a family medicine practice and frequency-matched to the clinical group for age and sex. Controls were screened by medical history for current psychiatric disorders, acute or chronic inflammatory conditions, recent infection, and immunomodulatory treatment. Exclusion criteria in both groups were autoimmune disease, chronic inflammatory or haematological illness, malignancy, infection during the previous four weeks, pregnancy or postpartum status, non-nicotine substance-use disorder, and immunomodulatory treatment. The systemic immune-inflammation index was derived from complete blood count parameters. Welch independent-samples t-tests compared continuous variables, Pearson chi-square tests assessed categorical variables, analysis of covariance tested the age- and sex-adjusted group difference, Cohen’s d estimated effect size, and receiver operating characteristic analysis explored discriminative performance.

Results

The two groups were demographically comparable. Mean age was 39.8 ± 10.7 years in the schizophrenia group and 39.1 ± 10.3 years in primary-care controls, t = 0.53, p = 0.597. Male sex distribution was similar between groups, 87/124 versus 89/128, 70.2% versus 69.5%, χ² = 0.01, p = 0.913. Mean systemic immune-inflammation index was significantly higher in the schizophrenia group than in controls, 628 ± 246 versus 498 ± 203, t = 4.57, p < 0.001, mean difference = 130, 95% confidence interval 73.9-186.1, with a moderate effect size, Cohen’s d = 0.58. The group difference remained significant in a minimally adjusted model including age and sex, analysis of covariance F = 20.6, p < 0.001, partial η² = 0.077. Receiver operating characteristic analysis showed limited discriminative performance, area under the curve = 0.66, 95% confidence interval 0.59-0.73.

Conclusions

Adults with clinician-confirmed DSM-5 schizophrenia showed significantly higher systemic immune-inflammation index values than demographically matched primary-care controls. However, the modest area under the curve indicates that this group-level inflammatory signal has limited individual-level discriminative value. The systemic immune-inflammation index should therefore be interpreted as a non-specific marker of peripheral immune load, not as a stand-alone diagnostic biomarker for schizophrenia. Residual confounding by metabolic and lifestyle variables should be considered.

References

  1. Carpentier, A., Zampetas, D., Durand, A., Naassila, M., Bralet, M.C., 2025. Relationships between immune-inflammatory features and social cognitive impairments in patients with schizophrenia spectrum disorders: a systematic review. Brain Behav. 15(4), e70384. doi:10.1002/brb3.70384.
  2. Zhou, L., Ma, X., Wang, W., 2024. Immune dysregulation is associated with symptom dimensions and cognitive deficits in schizophrenia: accessible evidence from complete blood count. BMC Psychiatry 24, 48. doi:10.1186/s12888-023-05430-3.
  3. Canli, D., 2024. Evaluation of systemic immune inflammation index and neutrophil-to-lymphocyte ratio in schizophrenia, bipolar disorder and depression. Bratisl. Lek. Listy 125(8), 472-476. doi:10.4149/BLL_2024_73.
  4. Bilgin Koçak, M., Öztürk Atkaya, N., Oruç, M.A., 2024. Evaluation of inflammatory markers obtained from complete blood count in different stages of schizophrenia. Curr. Med. Res. Opin. 40(8), 1413-1419. doi:10.1080/03007995.2024.2378180.
  5. Chen, K., Wang, L., Ning, H., Pan, H., Zhang, W., 2025. Neutrophil-to-lymphocyte ratio; platelet-to-lymphocyte ratio; systemic immune-inflammatory index: inflammatory indicators of cognitive impairment in schizophrenia patients. Front. Psychiatry 16, 1552451. doi:10.3389/fpsyt.2025.1552451.