Antipsychotic drugs result in the formation of immature neutrophil leucocytes in schizophrenic patients

Abstract

Subclinical abnormality of neutrophil populations of patients suffering from schizophrenia and medicated with antipsychotic drugs was evaluated using cellular immaturity as a criterion. Neutrophil maturity of patients and controls was compared by determining mean nuclear lobularity in peripheral blood smears. White blood cell and neutrophil counts were made. Subjects were patients medicated with chlorpromazine (n = 17) or clozapine (n = 48). Controls (n = 58) were healthy, non-medicated clinical and academic staff. Determination of mean lobe number involved assessment of 300 neutrophils per individual. For subject and control groups, means and medians of mean lobe numbers and mean white cell and neutrophil counts were determined. Means for each group were compared using the Mann-Whitney U-test; variances using F ratios. Means of lobe numbers of both patient populations were significantly different (p < 0.0001) compared to controls. Two-thirds of patients had mean lobe numbers outside the control range. Dose-response (mean lobe number) plots were significant for patients medicated with both chlorpromazine and clozapine. White cell and neutrophil counts in patients and controls did not differ significantly. For six patients, mean lobe numbers were obtained before and after medication commenced and all showed lowering of mean lobe number. The mean lobe number of the one patient who subsequently suffered from agranulocytosis was at the low end of the patient range. Thus, patients medicated with antipsychotic drugs typically have immature neutrophils, but normal white cell and neutrophil numbers. This effect is probably drug-induced. Mean lobe number may predict patients at risk from agranulocytosis.

Haematological toxicity of drugs used in psychiatry

“…Of the drugs studied (flupenthixol, fluphenazine, haloperidol, thioridazine, trifluoperazine, olanzapine, risperidone and sulpiride), fluphenazine and sulpiride had by far the smallest effect on mean nuclear lobularity, a measure of neutrophil immaturity. Total leucocyte and neutrophil counts in patients and controls were not significantly different (Delieu et al, 2001(Delieu et al, , 2006.…”

Clozapine Promotes the Proliferation of Granulocyte Progenitors in the Bone Marrow Leading to Increased Granulopoiesis and Neutrophilia in Rats

“…Leukocyte differentials were calculated from blood smears stained with Giemsa-Wright-like stain (CAMCO Stain Pak, Cambridge Diagnostic Products, Inc., Fort Lauderdale, FL) by manually classifying a minimum of 100 leukocytes per slide. Furthermore, the number of nuclear lobes in the neutrophils were quantified manually following the method described by Delieu et al 5 Briefly, a minimum of 50 neutrophils were classified per slide as having one to six nuclear lobes. Some serum samples were analyzed for G-CSF by ELISA according to the kit's protocol (R&D Systems Inc., Minneapolis, MN).…”

Loss-of-function of neuroplasticity-related genes confers risk for human neurodevelopmental disorders

“…In contrast, antipsychotics appear to induce an immature granulocytic phenotype [45]. This has generally been considered a side-effect (and is separate from potentially fatal agranulocytosis, as induced by clozapine [46]), but neutrophils in drug-free individuals with schizophrenia generate elevated reactive oxygen species (ROS) [47,48] and ROS levels can be normalized by antipsychotics [49,50].…”