Paraoxonase 1 activity and lipid profile in schizophrenic patients

Asian Journal of Psychiatry 06/2014; 9. DOI: 10.1016/j.ajp.2013.12.019


This study aimed to investigate the variations of paraoxonase 1 (PON1) activity and lipid profile in patients with schizophrenia and the association of this activity with the sociodemographic, clinical and therapeutical characteristics of this population.

Patients and methods
Our cross-sectional study included 140 schizophrenic patients and 119 control subjects aged respectively 37.3 ± 10.4 and 41.4 ± 10 years. PON1 activity was determined using Konelab 30™ equipment (Thermo Electron Corporation). Plasma Total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (c-HDL) and low-density lipoprotein cholesterol (c-LDL) concentrations were determined using Cobas 6000™ (Roche diagnostics); apolipoproteins (ApoA1, ApoB) and lipoprotein (a) (Lp(a)) were determined using Integra 400 plus (Roche diagnostics).

Compared to controls, patients had no significant decrease of PON1 activity and significantly lower ApoA1, c-HDL levels, and significantly higher levels of TG, ApoB, Lp(a) and TC/c-HDL and ApoB/ApoA1 ratios. Furthermore, PON1 activity was correlated with TG/c-HDL ratio. The lowest PON1 activity was noted in obese patients, in paranoid sub-type and in patients treated with combination of typical and atypical antipsychotics without significant difference. Moreover, it was associated with gender and cigarette smoking but not with alcohol consumption status.

Schizophrenic patients had a decrease in PON1 activity and perturbations in their lipid profiles that contribute to increase the risk of cardiovascular diseases. In addition, our results revealed that there was no association between the decrease of PON1 activity and any demographic or clinical characteristics. Therefore, such patients require specific care, particularly with regard to their lipid profile.

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    • "Paraoxonase 1 (PON1) is an antioxidant enzyme synthesized by the liver and bound to highdensity lipoprotein (HDL), protecting HDL particles against OS damage (Precourt et al., 2011). In schizophrenia, there are only few data on PON1, reporting both normal and reduced activity (Gilca et al., 2014; Mabrouk et al., 2014; Unsal et al., 2013). No studies, however, examined PON1 activity in drug naïve individuals separately . "
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    ABSTRACT: Schizophrenia is accompanied by increased lipid peroxidation and nitric oxide (NO) levels and by lowered antioxidant levels. However, the effect of antipsychotic agents on these processes remains unclear. The objective of this study is to determine the oxidative stress (OS) status in drug naïve first-episode psychotic patients (FEP) compared to healthy controls and to delineate the effects of risperidone on these biomarkers. 51 drug naive FEP patients and 61 healthy controls were enrolled; FEP patients were reassessed 11 weeks after risperidone treatment. Three OS biomarkers, i.e. lipid hydroperoxides - LOOH, NO metabolites - NOx, and advanced oxidation protein products - AOPP, and two antioxidant biomarkers, i.e. total radical-trapping antioxidant parameter - TRAP, and paraoxonase 1 - PON1, were measured. The Positive and Negative Syndrome Scale (PANSS) and the Calgary Depression Scale for Schizophrenia (CDSS) were used to measure symptoms severity. Significantly lower PON1 activity and increased TRAP values were found in FEP patients. There were no significant associations between any of the OS/antioxidant biomarkers and clinical data. Risperidone treatment significantly increased PON1 activity and decreased LOOH levels. These effects of risperidone were not significantly associated with the clinical response and risperidone dosage. Changes in antioxidant profile, but not in lipid or protein oxidation or increased NO production, were found in drug-naive FEP. Risperidone may have antioxidant effects by lowering lipid peroxidation and increasing the antioxidant defenses against lipid peroxidation related to PON1. None of the biomarkers predicted treatment outcome. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Journal of Psychiatric Research 09/2015; 68:210-216. DOI:10.1016/j.jpsychires.2015.07.003 · 3.96 Impact Factor
  • Asian Journal of Psychiatry 01/2015; 14. DOI:10.1016/j.ajp.2015.01.003
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    ABSTRACT: Activated immune-inflammatory pathways play an important role in the pathophysiology of schizophrenia. Paraoxonase 1 (PON1) activity is inversely associated with inflammatory responses in numerous clinical conditions. The aims of this study were to delineate serum arylesterase PON1 activity in drug-naïve first episode psychosis (FEP) patients and a healthy control group, and to assess whether there are inverse relationships between PON1 activity and cytokine levels. A total of 51 drug-naïve FEP patients and 61 healthy controls were enrolled in this study. Levels of interleukin (IL)-4, IL-10, IL-6, tumor necrosis factor (TNF)-α and activity of PON1 were quantified. Compared to healthy controls, FEP patients showed lower serum PON1 activity and higher levels of IL-4, IL-10 and TNF-α. A significant inverse relationship between PON1 activity and IL-4, IL-6 and IL-10 levels was detected, but not for TNF-α. Subjects with very low PON1 activity (25th quartile) presented significantly higher levels of IL-6, IL-10 and IL-4 than those with higher PON1 activity (75th quartile). The present study provides evidence that FEP is characterized by an inverse relationship between lowered activity of the anti-inflammatory/antioxidant enzyme PON1 and increased cytokine levels, including IL-6, IL-4 and IL-10. It is hypothesized that lowered PON1 activity may play a role in the immune-inflammatory response that accompanies FEP and that increased cytokine levels may further modulate PON1 activity. Copyright © 2015. Published by Elsevier B.V.
    Schizophrenia Research 06/2015; 166(1-3). DOI:10.1016/j.schres.2015.06.009 · 3.92 Impact Factor