Abstract
Immune dysfunction has been implicated in the pathophysiology of schizophrenia. Leukocyte migration to the site of inflammation is a fundamental step of immune response which involves P-, E-, and L-selectins. Elevated selectin levels have been reported in un-medicated first-episode patients with schizophrenia but not in medicated patients with multi-episode schizophrenia. We measured fasting plasma soluble P-, E-, and L-selectin in 39 medicated patients with multi-episode schizophrenia and 19 healthy controls. In patients, psychotic symptom severity and cognitive function were assessed with the Positive and Negative Syndrome Scale (PANSS) and the NIH Toolbox Cognitive Test Battery respectively. C-reactive protein (CRP) and Body Mass Index (BMI) were measured in patients and controls. Comparison of selectin levels between patients and controls was done with t-tests and linear regression. Pearson correlation coefficients between plasma selectins and PANSS and cognitive measures were calculated. Geometric mean plasma soluble L-selectin level was lower in patients compared to controls from unadjusted (606.7 ± 1.2 ng/ml vs. 937.7 ± 1.15 ng/ml, p < 0.001) and adjusted analyses (β = 0.59; CI 0.41 to 0.88, p = 0.011). There was a trend towards higher plasma soluble P-selectin in patients compared to controls (90.4 ± 1.2ng/ml vs. 71.8 ± 1.2ng/ml, p = 0.059) in the unadjusted analysis. There was no association between the selectins and psychotic symptoms or cognitive function in the patients. In addition, the selectins were not significantly associated with CRP or BMI. The limitations of this study include small sample size and unavailability of information on medications and blood cell counts. The potential utility of soluble L-selectin as a biomarker of antipsychotic exposure in patients with schizophrenia and the concomitant change in immune response with the use of antipsychotics should be further evaluated.
Highlights
Findings from previous studies suggest that peripheral inflammation may lead to the activation of immune responses in the central nervous system [1,2], which may involve the induction of cytokines and adhesion molecules, recruitment of immune cells, and the activation of microglia [3,4]
We evaluated the association between plasma soluble selectin levels and psychotic symptoms and cognitive function respectively by calculating Pearson correlation coefficients between the selectins and Positive and Negative Syndrome Scale (PANSS) and NIH Toolbox scores
The main result of this study is that mean plasma sL-selectin level in medicated patients with schizophrenia is lower in comparison to the mean level in healthy controls
Summary
Findings from previous studies suggest that peripheral inflammation may lead to the activation of immune responses in the central nervous system [1,2], which may involve the induction of cytokines and adhesion molecules, recruitment of immune cells, and the activation of microglia [3,4]. Endothelial immune activation has potential relevance in the transmission of inflammation from the periphery to the brain but has not been adequately studied in schizophrenia. Findings from animal studies have shown that cell adhesion molecules of the selectin family are essential in the spread of inflammation from the periphery to the brain in the context of liver inflammation [10,11]
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