Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although it's well known that protein carbonyl (PCO) and advanced glycation end-products (AGEs) levels are elevated in plasma from patients with renal dysfunction, we recently identified patients who had no renal dysfunction but possessed high levels of plasma pentosidine (PEN), which is an AGEs, and low vitamin B6 levels in serum. In this study, we investigated the status of carbonyl stress to characterize the subtype of schizophrenia. When plasma samples were subjected to Western blot analysis for various AGEs, clear differences were only observed with the anti-PEN antibody in the plasma from schizophrenic patients. Moreover, we determined the formation of protein carbonyl (PCO), a typical indicator of carbonyl stress, occurred prior to the accumulation of PEN in the plasma of schizophrenic patients. PCO levels in the plasma from schizophrenic patients were significantly higher than that from healthy subjects. Western blots analysis clearly showed that albumin and IgG were markedly carbonylated in the plasma of some patients. Thus, PCOs may be a novel marker of carbonyl stress-type schizophrenia in addition to albumin containing PEN structure.
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PMID:Characterization of modified proteins in plasma from a subtype of schizophrenia based on carbonyl stress: Protein carbonyl is a possible biomarker of psychiatric disorders. 2643 70

Schizophrenia is characterized by an interrelated activation of the immune-inflammatory response system (IRS) and the compensatory immune-regulatory system (CIRS), which downregulates the IRS. Deficit schizophrenia is characterized by a deficit in IgM-mediated autoimmune responses to tryptophan catabolites. The presence and correlates of IgM isotype antibodies to oxidative-specific epitopes (OSEs), nitroso (NO), and nitro (NO2) adducts in schizophrenia remain unknown. This study measured IgM antibodies to malondialdehyde (MDA), azelaic acid, phosphatidylinositol, oleic acid, NO-tryptophan, NO-albumin, NO-cysteinyl, and NO2-tyrosine in a sample of 80 schizophrenia patients, divided into those with and those without deficit schizophrenia, and 38 healthy controls. Deficit schizophrenia was characterized by significantly lower IgM antibody levels to all OSEs as compared with non-deficit schizophrenia and controls. Lowered IgM antibodies to MDA coupled with increased IgM levels to NO-cysteinyl and NO2-tyrosine strongly predict deficit schizophrenia versus non-deficit schizophrenia with an area under the ROC curve of 0.913. A large part of the variance (21.2-42.2%) in the negative symptoms of schizophrenia and excitation is explained by IgM antibody titers to MDA (inversely) and NO-cysteinyl and/or NO2-tyrosine (both positively). Lower IgM antibodies to MDA are significantly associated with impairments in episodic memory including direct and delayed recall. These findings further indicate that deficit schizophrenia is a distinct phenotype of schizophrenia, which is characterized by lower natural IgM antibody levels to OSEs and relative increments in nitrosylation and nitration of proteins. It is concluded that deficits in natural IgM attenuate CIRS functions and that this impairment may drive negative symptoms and impairments in episodic memory and thus deficit schizophrenia.
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PMID:In Schizophrenia, Deficits in Natural IgM Isotype Antibodies Including those Directed to Malondialdehyde and Azelaic Acid Strongly Predict Negative Symptoms, Neurocognitive Impairments, and the Deficit Syndrome. 3048 13

Antipsychotic drugs interfere with the antioxidant defense system provoking complex and often toxicological effects. Here we examined differences in plasma albumin reduced free thiol (SH) group content and its reactivity as a consequence of clozapine (CLZ) and ziprasidone (ZIP) binding. Chronic administration of CLZ reduced, whereas treatment with ZIP increased albumin-SH content in rats. Regardless of the ratio of stearic acid (SA) bound to protein, in vitro binding of ZIP to human serum albumin (HSA) increased both the SH group level and reactivity. In contrast, the effect of CLZ on HSA-SH reactivity was dependent on HSA to SA molar ratio. CLZ binding was accompanied by an increase in HSA-SH reactivity in samples with normal, but a reduction of its reactivity level with higher SA/HSA ratio, compared to drug-free samples. We demonstrate by steady-state fluorescence quenching studies that an increase in SA binding to HSA is associated with a significant reduction of binding constant for both antipsychotics. In addition, this is the first report of quantitative characterization of ZIP binding to HSA. Our findings suggest that albumin-SH content and reactivity is modulated by ZIP towards an increased antioxidant defense capacity in circulation, as opposed to CLZ, which can contribute to the safer, more effective treatment of schizophrenia.
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PMID:Opposite clozapine and ziprasidone effects on the reactivity of plasma albumin SH-group are the consequence of their different binding properties dependent on protein fatty acids content. 3140 Mar 41

In schizophrenia, neuroactive vitamins A/D/E play vital neuroprotective roles in its pathophysiological processes. During medical treatment, atypical antipsychotics, including aripiprazole, amisulpride, olanzapine, and paliperidone, were widely used at present. However, their impact on vitamin metabolism in vivo remained unclear. In this study, we conducted a case-control research to investigate the impacts of antipsychotics on vitamin metabolism. Schizophrenic patients (n = 163), who were divided into 5 groups (aripiprazole group, amisulpride group, olanzapine group, paliperidone group, nonmedication group) according to their different medication patterns, and healthy controls (n = 75) were involved. The concentrations of vitamin A/D/E and antipsychotics were measured using liquid chromatography-tandem mass spectrometry methods. Compared with healthy controls, significantly lower vitamin D and E concentrations were found in the nonmedication group after covariance analysis adjusting for age, sex, albumin, bilirubin, triglyceride, and cholesterol. We found that aripiprazole could affect vitamin D concentrations in vivo, and a positive correlation between aripiprazole concentrations and vitamin D concentrations (r = 0.319, P = 0.025) was observed in aripiprazole group. Such result revealed the very first observation for the influence of atypical antipsychotics medication toward vitamin status in vivo. Our study showed that low concentrations of vitamin D and E in vivo could be associated with schizophrenia, suggesting that hypovitaminosis may lead to a vulnerability to schizophrenia. More importantly, aripiprazole may potentially benefit the patients through improving their vitamin D status in vivo.
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PMID:Effects of Atypical Antipsychotics on Neuroactive Vitamins in Patients With Schizophrenia. 3242 79


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