Vitamin B6 and schizophrenia

Accumulating evidence indicates that alterations in one-carbon metabolism may play an important role in the pathogenesis of schizophrenia. We focused on vitamin B6 (pyridoxal), which works as a coenzyme in one-carbon metabolism. We first conducted a case-control study and demonstrated that serum pyridoxal levels were significantly lower in the schizophrenia group than in the control group. Subsequently, we conducted a meta-analysis of case-control studies and achieved the similar result to the case-control study. Finally, we investigated the causality between serum pyridoxal levels and schizophrenia by a Mendelian randomization analysis. However, we could indicate no significant causality between serum pyridoxal levels and schizophrenia in the Japanese population. Further studies such as a longitudinal study will be needed because there are several studies on the benefits of vitamin B6 in schizophrenia

Synthesis of analogs of wasabi phytoalexin (methyl 1-methoxyindole-3-carboxylate)

金沢大学大学院自然科学研究科生理活性物質科学金沢大学薬学部Syntheses of wasabi phytoalexin analogs, such as 6-bromo-5-iodo, 2-bromo-5-iodo, 6-nitro, 5-chloroacetyl, and 6-chloroacetyl congeners, are reported. An interesting effect of the 1-methoxy group on the regioselectivity of electrophilic substitution reactions on indole nucleus is observed

Folate and gender in schizophrenia

Aim: Gender differences in serum folate concentrations are well known, but no studies have investigated the association between serum folate levels and schizophrenia based on gender. In this study in a Japanese population, we examined the difference in serum folate levels between patients with schizophrenia and non‐psychiatric controls stratified by gender. The relationships between serum folate levels, plasma total homocysteine (tHcy) and serum vitamin B6 (pyridoxal) levels were also examined using data from our previous studies. Methods: The serum folate concentrations of 482 patients diagnosed with schizophrenia and 1,350 non‐psychiatric control subjects were measured. We conducted an analysis of covariance to examine the differences in serum folate levels between the two groups based on gender. Spearman’s rank correlation was used to evaluate the relationships between folate, tHcy and vitamin B6 levels. Results: In the control group, serum folate concentrations were higher in women than in men. Lower levels of serum folate were observed in both male and female patients with schizophrenia. An inverse correlation between serum folate and plasma tHcy and a weak positive correlation between serum folate and vitamin B6 were observed in the combined cohort. Conclusion: Our findings suggest that (1) a low serum folate level may be associated with schizophrenia regardless of gender, and (2) folate administration may be beneficial for the treatment of schizophrenia. In schizophrenic patients with low serum folate levels, folate administration might result in improvements in high tHcy and an increase in low vitamin B6 levels

Blood glutamate levels were significantly higher in MDD patients

Purpose: There is growing evidence that glutamatergic signaling may be involved in major depressive disorder (MDD). In regard to peripheral blood glutamate changes in MDD, inconsistent findings have been reported. The purpose of the present study was to evaluate whether blood glutamate levels differed between MDD patients and control participants. Materials and methods: We conducted a systematic review and meta-analysis of 12 association studies between blood glutamate levels and MDD in a total of 529 MDD patients and 590 controls. Subsequently, we conducted subgroup analyses and a meta-regression analysis to examine the sources of potential heterogeneity. Results: A random effects model showed that blood glutamate levels were significantly higher in MDD patients than in controls (standardized mean difference=0.54, 95% CI=0.27–0.82, p=8.5×10-5) with high heterogeneity (I2=75.0%, p<0.05). Subgroup analyses showed elevated glutamate levels in MDD patients compared with controls in plasma, but not serum studies, and in studies using high-performance liquid chromatography but not with mass spectrometry for glutamate assay. A meta-regression analysis showed no effects of age, gender, medication use, sample size, and published year on blood glutamate levels. Conclusion: Our findings suggest that altered glutamate levels may be implicated in MDD, which provides further evidence of glutamatergic dysfunction in MDD

PrP in M2 macrophages and influenza

The cellular prion protein, PrPC, is a glycosylphosphatidylinositol anchored-membrane glycoprotein expressed most abundantly in neuronal and to a lesser extent in non-neuronal cells. Its conformational conversion into the amyloidogenic isoform in neurons is a key pathogenic event in prion diseases, including Creutzfeldt-Jakob disease in humans and scrapie and bovine spongiform encephalopathy in animals. However, the normal functions of PrPC remain largely unknown, particularly in non-neuronal cells. Here we show that stimulation of PrPC with anti-PrP monoclonal antibodies (mAbs) protected mice from lethal infection with influenza A viruses (IAVs), with abundant accumulation of anti-inflammatory M2 macrophages with activated Src family kinases (SFKs) in infected lungs. A SFK inhibitor dasatinib inhibited M2 macrophage accumulation in IAV-infected lungs after treatment with anti-PrP mAbs and abolished the anti-PrP mAb-induced protective activity against lethal influenza infection in mice. We also show that stimulation of PrPC with anti-PrP mAbs induced M2 polarization in peritoneal macrophages through SFK activation in vitro and in vivo. These results indicate that PrPC could activate SFK in macrophages and induce macrophage polarization to an anti-inflammatory M2 phenotype after stimulation with anti-PrP mAbs, thereby eliciting protective activity against lethal infection with IAVs in mice after treatment with anti-PrP mAbs. These results also highlight PrPC as a novel therapeutic target for IAV infection

Altered KYN/TRP, Gln/Glu, and Met/methionine sulfoxide ratios in the blood plasma of medication-free patients with major depressive disorder

Capillary electrophoresis-time-of-flight mass spectrometry (CE-TOFMS) is a comprehensive, quantitative, and high throughput tool used to analyze metabolite profiles. In the present study, we used CE-TOFMS to profile metabolites found in the blood plasma of 33 medication-free patients with major depressive disorder (MDD) and 33 non-psychiatric control subjects. We then investigated changes which occurred in the metabolite levels during an 8-week treatment period. The medication-free MDD patients and control subjects showed significant differences in their mean levels of 33 metabolites, including kynurenine (KYN), glutamate (Glu), glutamine (Gln), methionine sulfoxide, and methionine (Met). In particular, the ratios of KYN to tryptophan (TRP), Gln to Glu, and Met to methionine sulfoxide were all significantly different between the two groups. Among the 33 metabolites with altered levels in MDD patients, the levels of KYN and Gln, as well as the ratio of Gln to Glu, were significantly normalized after treatment. Our findings suggest that imbalances in specific metabolite levels may be involved in the pathogenesis of MDD, and provide insight into the mechanisms by which antidepressant agents work in MDD patients

Altered KYN/TRP, Gln/Glu, and Met/methionine sulfoxide ratios in the blood plasma of medication-free patients with major depressive disorder

Capillary electrophoresis-time-of-flight mass spectrometry (CE-TOFMS) is a comprehensive, quantitative, and high throughput tool used to analyze metabolite profiles. In the present study, we used CE-TOFMS to profile metabolites found in the blood plasma of 33 medication-free patients with major depressive disorder (MDD) and 33 non-psychiatric control subjects. We then investigated changes which occurred in the metabolite levels during an 8-week treatment period. The medication-free MDD patients and control subjects showed significant differences in their mean levels of 33 metabolites, including kynurenine (KYN), glutamate (Glu), glutamine (Gln), methionine sulfoxide, and methionine (Met). In particular, the ratios of KYN to tryptophan (TRP), Gln to Glu, and Met to methionine sulfoxide were all significantly different between the two groups. Among the 33 metabolites with altered levels in MDD patients, the levels of KYN and Gln, as well as the ratio of Gln to Glu, were significantly normalized after treatment. Our findings suggest that imbalances in specific metabolite levels may be involved in the pathogenesis of MDD, and provide insight into the mechanisms by which antidepressant agents work in MDD patients

イワユル ビョウビョウ レンケイ ガ ソウコウ シタ ショウガイシャ ニ タイスル シュウガクテキ シカ チリョウ ニツイテ

In recent years, the oral environments of disabled people are well maintained by dental specialists for the disabled; however, because serious conditions requiring dental therapy do occur in disabled patients, we created a referral system for multidisciplinary dentistry for the disabled. In this report, we describe the successful implementation of this referral system and the treatment outcomes of disabled patients who underwent therapy by dental specialists. The patients were 12 disabled people, comprising 9 males and 3 females, who had been undergoing dental treatment in Tokushima Red Cross Hinomine Rehabilitation Center for People with Disabilities and had visited Tokushima University Hospital between January 2010 and March 2013. Their ages ranged from 14 to 71 years old, with a mean of 32.5 years old. The most common types of disabilities were hypophrenia: 7 patients (58.3%); cerebral palsy: 4 patients (33.3%), autism: 3 patients (25.0%), malformation syndrome: 2 patients (16.7%), etc. were found. The most frequent complications were epilepsy: 5 patients (41.7%); cured patent ductus arteriosus, laryngomalacia, asthma, hypertension, and ventilatory impairment were found in 1 patient (8.3%). Regarding oral diseases, chronic periodontitis and dental caries: 11 cases (91.7%), impacted wisdom teeth and persistence of deciduous teeth: 2 cases (16.7%) and oral cancer: 1 case (8.3%), were found. Concerning treatment, tooth extraction: 11 cases (91.7%), crown restoration: 5 cases (41.7%), pulpectomy: 2 cases (16.7%) and tumor resection: 1 case (8.3%), were safely performed. The procedures were performed under intravenous sedation in 6 cases, and under general anesthesia in the other 6 cases. Our referral system may contribute to the development of low-risk dentistry for the disabled

Decreased serum pyridoxal levels in schizophrenia : meta-analysis and Mendelian randomization analysis

Background: Alterations in one-carbon metabolism have been associated with schizophrenia, and vitamin B6 is one of the key components in this pathway. Methods: We first conducted a case–control study of serum pyridoxal levels and schizophrenia in a large Japanese cohort (n = 1276). Subsequently, we conducted a meta-analysis of association studies (n = 2125). Second, we investigated whether rs4654748, which was identified in a genome-wide association study as a vitamin B6-related single nucleotide polymorphism, was genetically implicated in patients with schizophrenia in the Japanese population (n = 10 689). Finally, we assessed the effect of serum pyridoxal levels on schizophrenia risk using a Mendelian randomization (MR) approach. Results: Serum pyridoxal levels were significantly lower in patients with schizophrenia than in controls, not only in our cohort, but also in the pooled data set of the meta-analysis of association studies (standardized mean difference –0.48, 95% confidence interval [CI] –0.57 to –0.39, p = 9.8 × 10–24). We failed to find a significant association between rs4654748 and schizophrenia. Furthermore, an MR analysis failed to find a causal relationship between pyridoxal levels and schizophrenia risk (odds ratio 0.99, 95% CI 0.65–1.51, p = 0.96). Limitations: Food consumption and medications may have affected serum pyridoxal levels in our cross-sectional study. Sample size, number of instrumental variables and substantial heterogeneity among patients with schizophrenia are limitations of an MR analysis. Conclusion: We found decreased serum pyridoxal levels in patients with schizophrenia in this observational study. However, we failed to obtain data supporting a causal relationship between pyridoxal levels and schizophrenia risk using the MR approach