Plasma soluble L-selectin in medicated patients with schizophrenia and healthy controls

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.

Reduced levels of circulating adhesion molecules in adolescents with early-onset psychosis

“…Moreover, although Kronig et al found decreased levels of sICAM in adults with SZ 29 , Stefanovic et al found that early-stage SZ patients had similar levels to that of HC, and they also observed increased levels of sICAM in older patients with a longer duration of illness 32 . Increased levels of sP-selectin were shown in adult patients with acute psychosis and AP exposure 30 , whereas Mohite et al reported no difference between HC and medicated, multi-episode patients 31 . As discussed above, these inconsistent findings could partly reflect variations in demographic characteristics between samples.…”

“…Reports on circulating levels of CAMs in adults with psychosis compared with healthy controls (HC) have been inconsistent, and both higher, lower, and similar levels of ICAM-1, VCAM-1, E-, L-, and P-selectin have been reported [27][28][29][30][31][32][33] . Because increased levels of several of these CAMs are associated with cardiometabolic risk factors and disease in the general population 34 , differences in demographics and comorbidity combined with staging differences could explain the inconsistency in reported levels 32 .…”

Systemic Cell Adhesion Molecules in Severe Mental Illness: Potential Role of Intercellular CAM-1 in Linking Peripheral and Neuroinflammation

“…These CAMs may shed from the cell surface by different mechanisms and their soluble (s) form released into the circulation. As shown in Supplemental Table 1, many previous studies have evaluated circulating CAMs showing quite consistent upregulation of proteins such as sICAM-1 in SMI [18,[31][32][33][34][35][36][37], while inconsistent regulation is found for sVCAM-1 [31][32][33][34] and sP-SEL [38][39][40][41][42], possibly due to differences in sample material and controlling for different demographics. To our knowledge, systemic levels of sJAM-A and sN-CAD, have not been evaluated in SMI.…”

Vascular-related biomarkers in psychosis: a systematic review and meta-analysis

“…Blood zonulin was also elevated in the patients (SMD, 1.17; 95% CI, 0.04-2.30; p = 0.043) (80,81). We found no significant differences between all patients and controls for blood E- (82)(83)(84) or P-selectins (82,(84)(85)(86), intercellular adhesion molecule 1 (ICAM-1) 83, 86-93), vascular cell adhesion molecule 1 (VCAM-1) (83, 86,88,90,91,93), tissue inhibitor of matrix metalloproteinase1 (TIMP-1) (79, 94), TIMP-2 (79, 94), or plasminogen activator inhibitor-1 (PAI-1) (95-97). However, blood ).…”