![]() Furthermore, some of these biomarkers have been observed to differ according to sex. In addition, high raw monocyte counts have also been correlated with the presence of schizophrenia. All three markers show higher levels in schizophrenia during relapse than during remission. Though they are less well-studied than the NLR, some reports suggest that they also may reflect inflammatory/anti-inflammatory processes in schizophrenia and its treatment. The monocyte-to-lymphocyte ratio (MLR) and the platelet-to-lymphocyte ratio (PLR) are two other accessible blood biomarkers. There are reports of further sex/gender differences in schizophrenia in: neuroanatomical characteristics, clinical manifestations, and disease progression. There is a positive relationship among cognition, sex hormones, and inflammatory markers. Concerning sex/gender differences, most studies report better overall cognitive function in women with schizophrenia than in men. While we have found no studies on the relationship between the NLR and cognition in schizophrenia, this marker has been shown to be inversely related to cognitive test scores in bipolar disorder. An elevated NLR is also significantly associated with an increased risk of mild cognitive impairment. The NLR increases with the severity of psychopathology in schizophrenia and decreases with antipsychotic administration. NLR is increased relative to the general population in both first-episode psychosis and chronic forms of schizophrenia, but, especially in the latter, antipsychotic effects constitute a confounding factor. ![]() It is, thus, a marker of pathogenetic inflammation, which plays an important part not only in schizophrenia but also in several medical conditions – e.g., cardiovascular disease. The NLR links the innate immune response, represented by neutrophils, to adaptive immunity, represented by lymphocytes. Requiring only an inexpensive and relatively unintrusive Complete Blood Count (CBC), this accessible biomarker can be easily measured by dividing the absolute neutrophil count by the lymphocyte count. It has substantial relevance as a biomarker due to its simplicity and ready availability. The neutrophil-to-lymphocyte ratio (NLR) is a reasonably good marker of systemic inflammation that correlates with cardiac events and mortality related to many cardiovascular diseases. As current dosing guidelines make no sex-specific recommendations, leaving women open to cumulative adverse effects, biomarkers indicative of treatment response need urgently to be developed. Due, at least in part, to these mechanisms, women with schizophrenia of childbearing age need lower doses of antipsychotics than men. Estrogen has direct antipsychotic effects at brain receptor sites and modulates the metabolism of some (not all) antipsychotics. Cardiovascular death, for instance, to which men are generally more susceptible than women, is disproportionately increased in women by antipsychotic treatment. The clinical impact of antipsychotics differs depending on patient sex. Therefore, identifying neuroinflammatory biomarkers in schizophrenia may be useful in diagnosis, in determining optimal antipsychotic dose, and in tracking treatment efficacy. Pro-inflammatory cytokines play a role in neurogenesis, and treatment with antipsychotic medications may, to some extent, work by inducing anti-inflammatory and antioxidant effects. Schizophrenia is widely considered to be an inflammatory disease associated with chronic neural and systemic inflammation. 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. ![]() Higher doses of antipsychotics were associated with worse working and semantic memory and mental flexibility in women with schizophrenia. Higher doses of antipsychotics are associated with worse working and semantic memory and mental flexibility in the women in our sample. In women, the NLR and the PLR correlate positively with antipsychotic drug dose and inversely with a working memory test (Direct Digit Span). We found that the NLR and the PLR are higher among women with schizophrenia when compared with men. 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. 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.
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