Schizophrenia risk loci from xMHC region were associated with antipsychotic response in chronic schizophrenic patients with persistent positive symptom

We examined whether common variants from the extended major histocompatibility complex (xMHC) region contribute to the response to antipsychotic drugs (APDs) in patients with schizophrenia with persistent psychosis. Subjects participated in a prospective longitudinal study of the effect of APDs on psychopathology were temporally split into discovery (n = 88) and replication (n = 42) cohorts. The primary endpoint was a change in Brief Psychiatric Rating Scale at 6-week or 6-month after treatment. rs204991 (β = 3.917, p = 3.72 × 10−6), the strongest signal associated with response at 6-week was located near C4A/C4B after a linear regression adjusted for covariates. xMHC SNP imputation disclosed much stronger signals (rs9268469, β = 5.140, p = 1.57 × 10−7) and other weaker signals (p \u3c 1 × 10−5) spanning the entire xMHC region. All the variants were previously identified schizophrenia risk loci. Conditional fine-mapping revealed three subgroups of SNPs which were the eQTLs (p \u3c 1 × 10−7) for C4A, HLA-C, and BTN3A2 in disease-relevant tissue. Epistasis between HLA-C and C4A was observed (p = 0.019). Minor allele (G) carriers of rs204991, eQTL for C4A, having decreased risk for schizophrenia and lower imputed expression of C4A, had a better response to APDs. Some imputed HLA alleles associated with a decreased risk for schizophrenia had a positive association with improvement in psychotic symptoms. An independent cohort validated the association of change in psychosis with C4A. We provide evidence that genetic risk factors for schizophrenia from the xMHC region are associated with response to APDs and those variants significantly alter the imputed expression of C4A, HLA-C, and BTN3A2. The minor alleles predicting higher C4A level are associated with diminished improvement in psychotic symptoms after APD treatment

日本人統合失調症患者におけるNMDA受容体機能低下仮説に基づく候補遺伝子解析

学位の種別: 課程博士審査委員会委員 : (主査)東京大学教授 尾藤 晴彦, 東京大学教授 辻 省次, 東京大学准教授 後藤 順, 東京大学教授 徳永 勝士, 東京大学教授 水口 雅University of Tokyo(東京大学

Pharmacogenetics of asthma in children

Allergic diseases such as bronchial asthma and atopic dermatitis develop by a combination of genetic and environmental factors. Several candidate causative genes of asthma and atopy have been reported as the genetic factors. The clinical features of patients and causes of diseases vary. Therefore, personalized medicine (tailor-made medicine) is necessary for the improvement of quality of life (QOL) and for asthma cure. Pharmacogenetics is very important for personalized medicine. Here, we present the genetics and pharmacogenetics of asthma in children. Finally, we show the guideline for personalized medicine for asthma, particularly in childhood, including the pharmacogenetics of anti-asthmatic drugs, preliminarily produced by the authors

The creativity of the meaning of the dream in PCAGIP Dreamwork : How a horror nightmare turned into a friendship dream

本研究では、夢PCAGIPにおいて夢提供者自身が、夢の体験過程が促進された場面を特定し、そこでの相互作用及び意味の生成過程について検討し考察した。夢PCAGIPは8名のメンバーで行われ、Participant-Observer方式を採用した。すなわち、「被験者」が同時に「実験者」であった。ワークの結果、夢提供者自身の体験が促進された場面は全13場面であり、それらの場面における体験の促進要因は6つにパターン化された。さらに、これら6つのパターンから4つの観点が導き出された。それらは、夢の精緻化、夢の拡張と再構成化、追体験と交差による夢の文脈の変化、現実との交差による夢の意味の創造であった。In this study of the PCAGIP Dreamwork process, the dreamer identified instances where the experiencing of the dream was carried forward. The interaction and generation of meaning in these instances were examined and discussed. PCAGIP Dreamwork was conducted with eight members using a participant-observer methodology, where the subject of the study was also the researcher. As a result of the PCAGIP Dreamwork process, 13 instances were identified where dream experiencing was carried forward. The authors specified 6 patterns of interaction between the dreamer and the group member who was interacting at the moment when each of these 13 instances were observed. Furthermore, 4 observations were derived from the 6 patterns; these include refining the dream, extending and reconstituting the dream, the change in the dream context as a result of re-experiencing and crossing, and creation of the dream\u27s meaning by crossing the dream and reality

ショクジ セッシュ キジュン 2010ネンバン ニ ヨル カンリ エイヨウシ ヨウセイ カテイ ノ ジョシ ガクセイ ノ エイヨウ シンタイ カツドウ ヒョウカ

The purpose of this study was to assess the nutritional status of women university students in the third-grade of a registered dietitian training course, based on the Dietary Reference Intakes for Japanese(2010). We initially selected 46 students, and obtained valid responses from 41 students(89.1%). We performed body measurements, blood tests, a dietary weighing method for 3 days, and the measurement of physical activity by the accelerometer. In regard to the physique and blood test of the subjects, 24.4% were underweight, 4.9% were obese and 20.0% were anemic. The dietary weighing method showed that the rate of women who took vitamin C below the estimated average requirement was 90.0%, that of folic acid, iron and calcium were 41.0%, 83.0%, and 68.0% respectively. While the rate of salt intake greater than the dietary goal (7.5g/day)was 36.5%, the rate of fat energy ratio greater than the dietary goal(30%)was 31.7%. The average number of steps per day was 8,907 ± 2,293. These results showed that there was an overall insufficient intake of total energy, vitamins, and minerals, indicating that further nutritional management for the women students is required

An illustrated and annotated checklist of fishes on Kitami-Yamato Bank, southern Sea of Okhotsk

An annotated checklist of benthic fishes on the western part of Kitami-Yamato Bank off northeastern Hokkaido, Japan in the southern Sea of Okhotsk, is presented based on voucher specimens with accompanying color photographs. All material was collected in late April, 2013 and 2014 by the bottom trawl net, a total of 450 specimens being classified into 92 species representing 21 families. These include Bathyraja trachouros, the first record from the Sea of Okhotsk, and Careproctus segaliensis, only the second confirmed record of the species

Path Analysis of Tiller Density of Winter Wheat Demonstrates the Importance of Practices that Manipulate Clod Size Based on Soil Moisture at Seeding in the Rice–Wheat Cropping System

The moisture of paddy soil after rice cropping is a major impediment to the establishment, tillering and yield of winter wheat in the rice−wheat (R−W) cropping system. We examined the seedling establishment ratio, based on soilmoisture at seeding by path analysis of nine soil/plant traits in the farmer's fields in Western Japan where the R−W cropping system was being used, to establish a strategy for improving tiller density by optimizing the seedling establishment ratio. The clod size of surface soil, which showed a significant positive correlation with soil moisture at seeding, had a significant negative direct effect on the seedling establishment ratio. The reduction in seedling establishment ratio, together with fewer tillers per plant, resulted in a significant decrease in tiller density. The sum total of contribution of soil moisture contents to tiller density via clod size was smaller than that of seeding rate, and similar to that of the amount of nitrogen (N) basal dressing. This indicates that manipulating clod size based on soil moisture at seedingprovides an opportunity for maintaining tiller density, as well as changing the amount of N basal dressing with the soil moisture conditions after rice cropping

Genetic Markers of Early Response to Lurasidone in Acute Schizophrenia

Prediction of treatment response by genetic biomarkers has potential for clinical use and contributes to the understanding of pathophysiology and drug mechanism of action. The purpose of this study is to identify genetic biomarkers associated with response to lurasidone, an atypical antipsychotic drug, during the first four weeks of treatment. One-hundred and seventy-one acutely psychotic patients from two placebo-controlled clinical trials of lurasidone were included. Genetic associations with changes in Positive and Negative Syndrome Scale total score at weeks one, two, and four were examined. Genotyping was done with the Affymetrix 6.0 microarray and associations were computed using PLINK regression model. Although genome-wide significance was not reached because of the small sample size, the top associations were with genes important for brain function. The top week one marker, rs6459950 (p = 7.05 × 10-7), was close to the sonic hedgehog gene (SHH), involved in neuronal differentiation and neurogenesis. The top week two marker, rs7435958, was a SNP of GABRB1, encoding the GABA A Receptor β1. Notably, week four markers included a SNP within PTCH1, a specific receptor for SHH, possibly involved in the week one response. Pathway enrichment analysis further supported the involvement of neuron differentiation and neurogenesis. Tissue enrichment analysis suggested enrichment of these genes in anterior cingulate cortex relevant to GABAergic modulation of neuronal connectivity. This is the first study to identify genes possibly associated with very early response to lurasidone. Further replication study is warranted and needed to determine the functional effects of the genetic markers