Discussion
inflammation, schizophrenia
INFLAMMATION, SECONDARY, CHRONIC INFLAMMATION
We found a higher NLR and a higher PLR in women with schizophrenia compared to men. These inflammatory markers were also inversely related to working memory in women. Moreover, higher doses of antipsychotics worsened working and semantic memory and mental flexibility in the women in our sample. No such correlations were present in men, suggesting that, as antipsychotic doses increase, women show deteriorating cognitive performance and an imbalance between inflammation and immunity.The cognitive areas most affected by antipsychotics were verbal working memory (as evaluated by the Digit Span task) and semantic memory (measured with the Animal Verbal Fluency test). Working memory is known to correlate with IQ [Many sex differences have been reported in schizophrenia [As the NLR and PLR correlate positively with the chlorpromazine equivalent dose of antipsychotics, it appears that female patients are more sensitive than males to the effects of these drugs, perhaps because some estrogen receptors (such as the G Protein-Coupled Estrogen Receptor 1) mediate anti-inflammatory effects and are under-expressed in individuals with schizophrenia [The NLR has been independently associated with the severity of psychopathology in schizophrenia; it decreases after antipsychotic administration [Our study has limitations. It is a secondary analysis of a small subgroup of patients, making it underpowered for the purposes of this study, so that Type I and Type II error cannot be excluded. Furthermore, there are many inflammatory biomarkers that we did not evaluate, which is a potential source of bias. Additionally, we have not addressed the many sources of potential acute or chronic inflammation in patients nor checked for use of anti-inflammatory drugs, all potential confounders of our results. Furthermore, ours is a cross-sectional, non-interventional study with no healthy control group, which contributes to possible biases. However, even though our sample was small, we had enough women in the study to find between-group differences. We consider these preliminary findings a relevant starting point for future studies purposely designed from the ground up to evaluate sex differences in the relationship between cognition, antipsychotics, and inflammatory markers in schizophrenia.