# Antipsychotics lower peripheral markers of inflammation in drug-naïve early psychosis: a pilot study

**Authors:** Nicole Šafářová, Marián Kolenič, Ivana Tašková, Václav Čapek, Petra Fürstová, Filip Španiel

PMC · DOI: 10.3389/fpsyt.2026.1769162 · Frontiers in Psychiatry · 2026-02-17

## TL;DR

This pilot study found that antipsychotic treatment in early psychosis patients reduces inflammation markers in the blood.

## Contribution

The study shows antipsychotics have a dose-dependent anti-inflammatory effect in drug-naïve early psychosis patients.

## Key findings

- Antipsychotic exposure predicted significant reductions in NLR, MLR, PLR, and SII.
- All associations remained significant after false discovery rate adjustment.
- The results suggest a consistent anti-inflammatory effect of antipsychotics in early psychosis.

## Abstract

Neuroinflammation is increasingly recognized as a core pathophysiological mechanism in schizophrenia and can be indirectly assessed through peripheral inflammatory markers. Therefore, this pilot study investigated the impact of antipsychotic treatment on inflammation in patients with first-episode psychosis (FEP) who were antipsychotic-naive at study entry.

Thirty-three drug-naïve FEP patients provided blood samples upon admission (V0) and follow-up (V1), from which peripheral inflammatory markers—i.e., neutrophil/lymphocyte ratio (NLR), monocyte/lymphocyte ratio (MLR), platelet/lymphocyte ratio (PLR), and systemic immune-inflammation index (SII)—were calculated. Antipsychotic doses during continuous hospitalization between V0 and V1 (34 days, IQR: 21–49 days) were converted into cumulative chlorpromazine equivalents (cCPZ).

In multiple regression models adjusting for sex, age, BMI, DUP, and clozapine use, cumulative antipsychotic exposure significantly predicted reductions in ΔNLR (p = 0.048), ΔMLR (p = 0.041), ΔPLR (p = 0.028), and ΔSII (p = 0.028). All associations remained significant following false discovery rate adjustment (pFDR = 0.048 for all outcomes).

These findings suggest a consistent dose-dependent anti-inflammatory effect during early antipsychotic treatment in FEP. Given the exploratory nature of this study, larger studies are needed to confirm these findings.

## Linked entities

- **Diseases:** schizophrenia (MONDO:0005090)

## Full-text entities

- **Genes:** IL2 (interleukin 2) [NCBI Gene 3558] {aka IL-2, TCGF, lymphokine}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, DRD2 (dopamine receptor D2) [NCBI Gene 1813] {aka D2DR, D2R}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, TLR4 (toll like receptor 4) [NCBI Gene 7099] {aka ARMD10, CD284, TLR-4, TOLL}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}
- **Diseases:** chronic low (MESH:D009800), bacterial infections (MESH:D001424), cognitive decline (MESH:D003072), CIN (MESH:D064146), neutropenia (MESH:D009503), viral or (MESH:D014777), insulin resistance (MESH:D007333), DUP (MESH:D011618), weight gain (MESH:D015430), dyslipidemia (MESH:D050171), SII (MESH:D007249), NLR (MESH:D015467), Schizophrenia (MESH:D012559), Neuroinflammation (MESH:D000090862), mental illness (MESH:D001523)
- **Chemicals:** CPZ (MESH:D002746), zuclopenthixol (MESH:D003006), levomepromazine (MESH:D008728), dopamine (MESH:D004298), PALI (MESH:D000069455), amisulpride (MESH:D000077582), ziprasidone (MESH:C092292), olanzapine (MESH:D000077152), paliperidone (MESH:D000068882), ARI (-), risperidone (MESH:D018967), Clozapine (MESH:D003024), haloperidol (MESH:D006220), CLO (MESH:D006997), Aripiprazole (MESH:D000068180)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

50 references — full list in the complete paper: https://tomesphere.com/paper/PMC12953376/full.md

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Source: https://tomesphere.com/paper/PMC12953376