Decrease in cognitive performance and increase of the neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios with higher doses of antipsychotics in women with schizophrenia: a cross-sectional study

Abstract

Background: We explored the relationship between symptoms, cognitive performance, neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) (three markers of inflammation), and antipsychotic dose (in chlorpromazine units) in male and female patients with schizophrenia.

Methods: We conducted a cross-sectional analysis in patients with schizophrenia of the complete blood count and the results of neuropsychological testing, using the Welch t-test to compare groups and the Pearson test for correlations.

Results: We found that the NLR and the PLR are higher among women with schizophrenia when compared with men. In women, the NLR and the PLR correlate positively with antipsychotic drug dose and inversely with a working memory test (Direct Digit Span). Higher doses of antipsychotics are associated with worse working and semantic memory and mental flexibility in the women in our sample.

Conclusion: Higher doses of antipsychotics were associated with worse working and semantic memory and mental flexibility in women with schizophrenia. No such correlations were present in men, suggesting that, in female patients, cognitive performance deteriorates as the antipsychotic dose is increased, a finding that could be mediated by inflammatory mechanisms, given the demonstrated relationship to biomarkers of inflammation - e.g., the NLR and the PLR.

Trial registration: NCT03788759 (ClinicalTrials.gov).

Keywords: Antipsychotics; Executive function; Inflammation; Neuropsychological tests; Neutrophil-to-lymphocyte ratio; Schizophrenia.

Fig. 1

NLR and PLR in Each Sex and their Relationship to Antipsychotic Dose and Working Memory in Women. A) Neutrophil-to-lymphocyte Ratio (NLR) in each sex (error bars indicate SEM, the asterisk indicates p < 0.05). B) Platelet-to-lymphocyte Ratio (PLR) in each sex (error bars indicate SEM, the asterisk indicates p < 0.05). C) Correlation between NLR and daily antipsychotic dose (in Chlorpromazine-equivalent, CPZ units) in women (n = 12). (D) Correlation between PLR and daily antipsychotic dose (in Chlorpromazine-equivalent, CPZ units) in women (n = 12). (E) Relationship between the Direct Digit Span Task and NLR in women (n = 11). (F) Relationship between the Direct Digit Span Task and PLR in women (n = 11)

Fig. 2

Correlation between Neuropsychological Tests and Antipsychotic Dose in Women. Correlation between neuropsychological tests (Digit Span task, Animal Verbal Fluency test, time taken in the Trail Making B test, and time and errors in the Stroop Colors test) and antipsychotic dose in CPZ units of females (n = 11)