Pro-inflammatory cytokine levels are elevated in female patients with schizophrenia treated with clozapine

Psychopharmacology (Berl). 2022 Mar;239(3):765-771. doi: 10.1007/s00213-022-06067-y. Epub 2022 Jan 26.

Abstract

Rationale and objective: In this study, we hypothesized that the chronic use of clozapine affects cytokine expression and has a greater effect on female patients than on male patients. The aims of this study were to detect (1) whether serum cytokine levels were altered in patients with chronic schizophrenia after clozapine treatment compared with age- and sex-matched healthy controls, (2) whether there was a gender difference in serum cytokine levels after clozapine treatment, and (3) whether there was a correlation between serum cytokine levels and clozapine daily dosage in patients with schizophrenia.

Methods: Forty-nine inpatients with schizophrenia treated with clozapine and fifty-three sex- and age-matched healthy controls were recruited. The patients' psychiatric symptoms were measured by the Positive and Negative Syndrome Scale (PANSS). Blood samples from both patients and healthy controls were collected. Serum IL-1β, IL-2, IL-6, IL-17, IFN-γ, and TNF-α levels were measured in duplicate by sandwich enzyme-linked immunosorbent assay.

Results: We found that chronic clozapine treatment in patients with schizophrenia resulted in the abnormal expression of serum cytokines, such as IL-2, IL-6, IL-17, and TNF-α, compared with the healthy controls. In addition, there was a gender difference in the abnormal expression of cytokines between male and female patients with schizophrenia. In the female group, IL-2 serum levels were lower than those in the male group. Interestingly, there was a positive correlation between serum IL-2 levels and the daily clozapine dosage in female patients with schizophrenia.

Conclusion: Findings from our study have shown clear evidence that clozapine had a greater effect on immune function in female patients with schizophrenia.

Keywords: Clozapine; Cytokine; IL-2; Schizophrenia; Woman.

MeSH terms

  • Antipsychotic Agents* / therapeutic use
  • Clozapine* / therapeutic use
  • Cytokines / blood*
  • Female
  • Humans
  • Male
  • Schizophrenia* / blood
  • Schizophrenia* / drug therapy

Substances

  • Antipsychotic Agents
  • Cytokines
  • Clozapine