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Objective: This study was to examine the alterations in metabolic parameters, anti-oxidant superoxide dismutase (SOD), inflammatory marker high-sensitivity C-reactive protein (hs-CRP) and microbiota after 24-week risperidone treatment in drug naïve, normal weight, first episode schizophrenia patients; the study further examined the relationship between metabolic changes and changes in microbiota.Methods: Forty-one patients completed the 24-week study and 41 controls were enrolled in this study. Metabolic parameters, SOD, hs-CRP and the copy numbers of 5 fecal bacteria were measured at baseline (both groups) and at different time points (patients only).Results: Patients had significantly lower numbers of fecal Bifidobacterium spp., Escherichia coli, Lactobacillus spp. compared with healthy controls (HC) (ps < 0.001); in contrast, the numbers of fecal Clostridium coccoides group were significantly higher in the patient group compared with HC (p < 0.001). After 24-week risperidone treatment, there were significant increases in body weight, BMI, fasting blood-glucose, triglycerides, LDL, hs-CRP, SOD and HOMA-IR (p < 0.001), significant increases in the numbers of fecal Bifidobacterium spp. and E. coli (ps < 0.001), and significant decreases in the numbers of fecal Clostridium coccoides group and Lactobacillus spp. (ps < 0.001). Hierarchical multiple linear regression analysis shows that after controlling for potential confounding variables, only the changes in fecal Bifidobacterium spp., among 4 types of fecal bacteria, entered into the model and significantly correlated with the changes in weight (unstandardized coefficient B = 4.413, R2 change = 0.167, p = 0.009) and BMI (B = 1.639, R2 change = 0.172, p = 0.008) after 24-week treatment.Conclusion: Drug naïve, first episode schizophrenia patients show abnormalities in microbiota composition. Risperidone treatment causes significant changes in certain fecal bacteria, which are likely associated with antipsychotic medication induced metabolic changes. [ABSTRACT FROM AUTHOR]

Abstract: Many genes associated with dopamine (DA) and norepinephrine (NE) systems influence cognitive deficits of schizophrenia patients, but one key enzyme is dopamine beta-hydroxylase (DBH), which converts DA to NE and whose activity and levels are under strong genetic control. This study examines the association of the 19bp insertion/deletion (Ins/Del) polymorphism in the 5′ flank of the DBH gene with cognitive deficits in first-episode schizophrenic patients (FEP). We assessed the cognitive function in 195 FEP and 304 healthy controls using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The 19bp Ins/Del polymorphism of DBH gene was genotyped. Our results showed that the allelic and genotypic frequencies of the 19bp Ins/Del polymorphism significantly differed between FEP and healthy controls (both p<0.05). Cognitive test scores were significantly lower in FEP than healthy controls on all scales (all p<0.001) except for the visuospatial/constructional index (p>0.05). Immediate memory abilities significantly differed by genotype (p<0.05) but not genotype×diagnosis. Immediate memory score was lower in FEP with DBH5′-Del/Del genotype (61.3±17.2) than those with DBH5′-Ins/Ins genotype (68.6±16.2; p<0.05). The 19bp Del allele was associated with poorer immediate memory performance than the Ins allele in FEP (p<0.05). However, healthy controls did not show any differences in cognitive function indices between the Ins and Del for either the allele or genotype of the 19bp Ins/Del polymorphism. Our findings suggest that the DBH5′-Ins/Del polymorphism may play a role in susceptibility to FEP. The DBH5′-Ins/Del polymorphism may also influence immediate memory in FEP. Moreover, FEP had poorer cognitive function than healthy controls in all examined cognitive domains except for the visuospatial/constructional index. [Copyright &y& Elsevier]

Abstract: Metabotropic glutamate receptor 5 (mGluR5) has been identified as a potential therapeutic target for schizophrenia, primarily due to its ability to indirectly modulate glutamatergic signalling through the NMDA receptor (NMDAR). Despite its potential, molecular studies characterising mGluR5 in schizophrenia are limited. We therefore aimed to determine if the mGluR5 binding site or protein levels were altered in schizophrenia or by current antipsychotics. Using in-situ radioligand binding and immunoblot, we measured [3H]MPEP binding to mGluR5 and mGluR5 protein density in the post-mortem dorsolateral prefrontal cortex (DLPFC; BA46) of 37 schizophrenia and 37 matched control subjects. Subsequently, we measured [3H]MPEP binding in rat brains following typical (haloperidol) or atypical (olanzapine) antipsychotic treatment (n=6/group). Subjects with schizophrenia showed no significant alteration in mGluR5 binding density or mGluR5 protein levels. Furthermore, mGluR5 binding in the rat cortex, thalamus, hippocampus and striatum was unaltered by short-, medium- and long-term antipsychotic treatment. Our data suggests that there are no alterations in mGluR5 in schizophrenia subjects. The lack of alteration in mGluR5 binding and protein in schizophrenia is advantageous because its ability to modulate the NMDAR is potentially unhindered, thereby supporting the development of novel antipsychotic agents that work through the mGluR5/NMDAR complex. [Copyright &y& Elsevier]