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Schizophrenia (SCZ) and bipolar disorder (BD) are severe mental disorders that pose important challenges for diagnosis by sharing common symptoms, such as delusions and hallucinations. The underlying pathophysiology of both disorders remains largely unknown, and the identification of biomarkers with potential to support diagnosis is highly desirable. In a previous study, we successfully discriminated SCZ and BD patients from healthy control (HC) individuals by employing proton magnetic resonance spectroscopy (1H-NMR). In this study, 1H-NMR data treated by chemometrics, principal component analysis (PCA) and supervised partial least-squares discriminant analysis (PLS-DA), provided the identification of metabolites present only in BD (as for instance the 2,3-diphospho-D-glyceric acid, N -acetyl aspartyl-glutamic acid, monoethyl malonate) or only in SCZ (as isovaleryl carnitine, pantothenate, mannitol, glycine, GABA). This may represent a set of potential biomarkers to support the diagnosis of these mental disorders, enabling the discrimination between SCZ and BD, and among these psychiatric patients and HC (as 6-hydroxydopamine was present in BD and SCZ but not in HC). The presence or absence of these metabolites in blood allowed the categorization of 182 independent subjects into one of these three groups. In addition, the presented data suggest disturbances in metabolic pathways in SCZ and BD, which may provide new and important information to support the elucidation and/or new insights into the neurobiology underlying these mental disorders. Image 1 [ABSTRACT FROM AUTHOR]

Backgroound 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. Methods 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. Results 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. Discussion 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. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To investigate possible differences in peripheral levels of chemokines, BDNF and oxidative markers between patients with Schizophrenia (SZ) and matched healthy controls, and investigate the correlation of these biomarkers with cognitive performance. Methods: Thirty individuals with SZ and 27 healthy controls were included and the following plasmatic biomarkers' levels were determined according to manufacturers' instructions: BDNF, TBARS, protein carbonyl content (PCC) and the chemokines CXCL-10/IP-10, CXCL-8/IL-8, CCL-11, CCL-24/Eotaxin-2, CCL-2/MCP-1, CCL-3/MIP-1. Selected neuropsychological tasks were administered to assess verbal learning (Hopkins Verbal Learning Test), verbal fluency (FAS test), working memory (Visual Working Memory Task, Keep Track Task, Letter Memory Task), set shifting (Plus–minus task, Number–letter task), inhibition (Computerized Stroop Task, Semantic Generation Task) and complex executive function tasks (Tower of London and the shortened version of the WCST-64). Results: Compared with the healthy control group, individuals with SZ presented significantly higher levels of BDNF and the chemokine CCL-11, and lower levels of TBARS and the chemokine CXCL-10/IP-10. When we examined only the SZ group, BDNF levels were positively correlated with semantic generation tasks. Working memory ability was negatively correlated with PCC. Regarding chemokines, CCL-11 was negatively correlated to performance in working memory test, and positively correlated with cognitive flexibility task. CXCL-8/IL-8 was positively correlated with verbal fluency. CCL-24/Eotaxin-2 was positively correlated with semantic generation ability and letter memory task. Conclusions: Our results indicate that cognitive performance in SZ is associated with mediators of neuroplasticity that can be measured peripherally. [Copyright &y& Elsevier]

Abstract: Background: Schizophrenia (SZ) has been associated with an imbalance in the inflammatory cytokine TNF-α. The objectives of this study were to compare TNF-α and its soluble receptors'' serum levels in individuals with SZ with the levels found in a group of healthy volunteers and to investigate the possible association between these biomarkers and the dimensions and severity of symptoms, clinical outcomes and response to treatment in patients with SZ. Methods: Fifty-four chronically medicated SZ outpatients and 118 healthy controls were included in the study. TNF-α levels were measured by Cytometric Bead Assay (CBA), and serum levels of soluble tumor necrosis factor receptor 1 (sTNFR1) and soluble tumor necrosis factor receptor 2 (sTNFR2) were measured by ELISA. Results: sTNFR1 and sTNFR2 were significantly elevated in patients with SZ as compared to the healthy control group. In the group of individuals with SZ, the levels of both types of soluble TNF receptors showed a negative correlation with global functioning. sTNFR1 levels were higher in the treatment-resistant patients as compared to the non-treatment-resistant patients and the controls. sTNFR1 levels were also heightened in patients with SZ and concomitant depression. Conclusion: Our findings reinforce that SZ is associated with an inflammatory profile and suggest that sTNFR1 is a marker of a treatment-resistance and severe clinical course in SZ. [Copyright &y& Elsevier]