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

Different Characteristics of Cognitive Impairment in Elderly Schizophrenia and Alzheimer's Disease in the Mild Cognitive Impairment Stage

We compared indices of the revised version of the Wechsler Memory Scale (WMS-R) and scaled scores of the five subtests of the revised version of the Wechsler Adult Intelligence Scale (WAIS-R) in 30 elderly schizophrenia (ES) patients and 25 Alzheimer's disease (AD) patients in the amnestic mild cognitive impairment (aMCI) stage (AD-aMCI). In the WMS-R, attention/concentration was rated lower and delayed recall was rated higher in ES than in AD-aMCI, although general memory was comparable in the two groups. In WAIS-R, digit symbol substitution, similarity, picture completion, and block design scores were significantly lower in ES than in AD-aMCI, but the information scores were comparable between the two groups. Delayed recall and forgetfulness were less impaired, and attention, working memory and executive function were more impaired in ES than in AD-aMCI. These results should help clinicians to distinguish ES combined with AD-aMCI from ES alone

Effect of Clozapine on DNA Methylation in Peripheral Leukocytes from Patients with Treatment-Resistant Schizophrenia

Clozapine is an atypical antipsychotic, that is established as the treatment of choice for treatment-resistant schizophrenia (SCZ). To date, no study investigating comprehensive DNA methylation changes in SCZ patients treated with chronic clozapine has been reported. The purpose of the present study is to reveal the effects of clozapine on DNA methylation in treatment-resistant SCZ. We conducted a genome-wide DNA methylation profiling in peripheral leukocytes (485,764 CpG dinucleotides) from treatment-resistant SCZ patients treated with clozapine (n = 21) in a longitudinal study. Significant changes in DNA methylation were observed at 29,134 sites after one year of treatment with clozapine, and these genes were enriched for “cell substrate adhesion” and “cell matrix adhesion” gene ontology (GO) terms. Furthermore, DNA methylation changes in the CREBBP (CREB binding protein) gene were significantly correlated with the clinical improvements. Our findings provide insights into the action of clozapine in treatment-resistant SCZ

ハママツシ ニ オケル ソウゾウ トシ ケイセイ ヘノ トリクミ

浜松市は日本有数の工業都市として発展してきたが、産業構造の転換期を迎え、大きな岐路に立たされている。こうした中、浜松市は、2009年3月に創造都市を目指す浜松市文化振興ビジョンを策定した。ここでは、文化創造を基盤とした創造的産業による持続的な都市の成長が目指されている。これを受けて、静岡文化芸術大学の研究プロジェクトチームは、浜松市、浜松商工会議所、浜松市文化振興財団の3者に呼びかけ、浜松創造都市協議会を設立した。浜松市は楽器産業の集積はあるが、音楽をはじめとした文化産業の集積がなく、雇用と所得をもたらす文化産業の振興が急務である。浜松創造都市協議会では、創造的人材が日常的に交流し、浜松発の創造的活動が産業として自立するための支援活動を開始したところである。Hamamatsu City has enjoyed economic growth and prosperity for many decades thanks to competitive manufacturingindustries. However, this city is confronted with momentous changes in its industrial structure. Under the strainedeconomic conditions, Hamamatsu City settled on a comprehensive plan of cultural policy in March 2009. This planemphasizes transformation into a "creative city" in which the creative industry with cultural capital drives sustainablegrowth. Therefore, our research project team established the Association for Creative City Hamamatsu in July 2009,a pioneering collaboration with the Hamamatsu Chamber of Commerce and Industry, Hamamatsu Cultural Foundation,and Hamamatsu City Government. Despite the presence of a cluster of musical instrument manufacturers, thecultural industry including the music industry, is underdeveloped in Hamamatsu City. Thus the growth of for-profit andnon-profit arts and cultural industries, which generate jobs and income, is very important. We have recently initiatedstrategic projects to network with creative people and nurture the arts and cultural industry in Hamamatsu City

Effect of Clozapine on DNA Methylation in Peripheral Leukocytes from Patients with Treatment-Resistant Schizophrenia

Clozapine is an atypical antipsychotic, that is established as the treatment of choice for treatment-resistant schizophrenia (SCZ). To date, no study investigating comprehensive DNA methylation changes in SCZ patients treated with chronic clozapine has been reported. The purpose of the present study is to reveal the effects of clozapine on DNA methylation in treatment-resistant SCZ. We conducted a genome-wide DNA methylation profiling in peripheral leukocytes (485,764 CpG dinucleotides) from treatment-resistant SCZ patients treated with clozapine (n = 21) in a longitudinal study. Significant changes in DNA methylation were observed at 29,134 sites after one year of treatment with clozapine, and these genes were enriched for “cell substrate adhesion” and “cell matrix adhesion” gene ontology (GO) terms. Furthermore, DNA methylation changes in the CREBBP (CREB binding protein) gene were significantly correlated with the clinical improvements. Our findings provide insights into the action of clozapine in treatment-resistant SCZ