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

<div><p>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.</p></div

Comparison of selectin levels in patients and control group.

<p>Comparison of selectin levels in patients and control group.</p

Comparison of demographic characteristics of patients and control group.

<p>Comparison of demographic characteristics of patients and control group.</p

Plasma soluble L-selectin in medicated patients with schizophrenia and healthy controls - Fig 1

<p><b>Plasma soluble L-selectin (A), P-selectin (B) and E-selectin (C) levels in patients with schizophrenia and healthy controls.</b> Error bars are representing 95% confidence intervals, and the little circle stands for the mean of the log-transformed value of each selectin. Plasma soluble P-, E- and L-selectin concentration were log transformed to normalize the data. Geometric means reported in the text were calculated by exponentiating mean log-transformed P-, E- and L-selectin for adjusted and unadjusted comparisons of patients and controls.</p

Socioeconomic Disadvantage Moderates the Association between Peripheral Biomarkers and Childhood Psychopathology

<div><p>Background</p><p>Socioeconomic disadvantage (SED) has been consistently associated with early life mental health problems. SED has been shown to impact multiple biological systems, including the regulation of neurotrophic proteins, immune-inflammatory and oxidative stress markers, which, conversely, have been reported to be relevant to physiological and pathological neurodevelopment This study investigated the relationship between SED, different domains of psychopathology, serum levels of interleukin-6 (IL6), thiobarbituric acid-reactive substance (TBARS) and brain-derived neurotrophic factor (BDNF). We hypothesized that a composite of socioeconomic risk would be associated with psychopathology and altered levels of peripheral biomarkers. In addition, we hypothesized that SED would moderate the associations between mental health problems, IL6, TBARS and BDNF.</p><p>Methods and Findings</p><p>Using a cross-sectional design, we measured the serum levels of IL6, TBARS and BDNF in 495 children aged 6 to 12. We also investigated socio-demographic characteristics and mental health problems using the Child Behaviour Checklist (CBCL) DSM-oriented scales. SED was evaluated using a cumulative risk model. Generalized linear models were used to assess associations between SED, biomarkers levels and psychopathology. SED was significantly associated with serum levels of IL6 (RR = 1.026, 95% CI 1.004; 1.049, p = 0.020) and TBARS (RR = 1.077, 95% CI 1.028; 1.127, p = 0.002). The association between SED and BDNF was not statistically significant (RR = 1.031, 95% CI 0.997; 1.066, p = 0.077). SED was also significantly associated with all CBCL DSM-oriented scales (all p < 0.05), whereas serum biomarkers (i.e. IL6, TBARS, BDNF) were associated with specific subscales. Moreover, the associations between serum biomarkers and domains of psychopathology were moderated by SED, with stronger correlations between mental health problems, IL6, TBARS, and BDNF being observed in children with high SED.</p><p>Conclusions</p><p>In children, SED is highly associated with mental health problems. Our findings suggest that this association may be moderated via effects on multiple interacting neurobiological systems.</p></div

Effects of interactions between high socioeconomic disadvantage and peripheral biomarkers on CBCL scales.

<p>All analyses included age, gender and ethnicity as covariates.</p

Mental health problems and peripheral biomarkers within socioeconomic disadvantage exposure subgroups.

<p>Correlations between (A) somatic problems and serum IL6; (B) attention deficit/hyperactivity problems and serum TBARS and (C) depressive problems and serum BDNF; within socioeconomic disadvantage exposure subgroups. SED: socioeconomic disadvantage; IL6: interlukin-6; TBARS: thiobarbituric acid-reactive substance; BDNF: brain-derived neurotrophic factor.</p

Definitions and descriptive statistics.

<p>Definitions and descriptive statistics.</p

Associations between socioeconomic disadvantage, IL6, TBARS and BDNF; considered separately (Model 1) and together (Model 2).

<p>All analyses included age, gender and ethnicity as covariates.</p