Abstract

BackgroundHigher inflammation has been identified in a substantial subset of both high-risk and chronically ill patients with schizophrenia and related psychoses and this may account for some of the heterogeneity of the schizophrenia. There is also much heterogeneity in cognitive deficits related to schizophrenia with some patients showing a marked decline from premorbid intellectual levels while others show little change from either normal or low intellect. However, the relationship between intellectual change with the illness onset and inflammation in schizophrenia has not been established.MethodsHere, we report the assessment of two common markers of inflammation from two independent samples of generally chronically ill patients with schizophrenia and related psychoses (one sample of 73 patients versus 70 healthy controls from Sydney, NSW, Australia and one sample of 297 patients from Syracuse, NY, USA). Peripheral venous blood samples were collected from all patients and blood markers of inflammation (C-Reactive Protein, CRP, and Neutrophil to Lymphocyte Ratio, NLR) were assayed using standard procedures. Assessment of premorbid and current intellectual abilities were obtained from the Sydney cohort of patients.ResultsGrouping the patients and controls from the Sydney sample into those with elevated (> 3 mg/L) versus normal (< 3 mg/L) CRP levels revealed 42% of the patients versus 20% of the healthy controls had elevated CRP (Chi Square = 9.16, p = .002) and further evidence of inflammation with an elevated mean NLR of 2.5. The frequency of peripheral inflammation was confirmed by the independent sample from Syracuse in which 39% of the patients (n= 115) had an elevated NLR above a cutoff score for normal of 2.2 which was consistent with the Sydney sample. Patients from the Sydney sample who had an elevated CRP also had a significant mean 15-point IQ decline from premorbid IQ levels, whereas the patients with CRP levels within normal limits did not show a statistically significant drop in IQ from premorbid levels (mean IQ decline 7.6 points). Healthy controls with normal CRP had no IQ change (0.0 points) and healthy controls with elevated CRP has a slight, non-significant IQ decline (mean 2.3 points).DiscussionThus, our study showed supportive evidence of elevated peripheral inflammation markers in subgroups of chronically ill patients with schizophrenia from two independent samples and a link between marked intellectual decline from premorbid levels and current peripheral inflammation in one chronically ill subgroup of patients with schizophrenia suggesting a role for inflammation in the cognitive impairment of a substantial proportion (40%) of patients with schizophrenia.

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