担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: We explored the gene expression levels in the brain of 3xTg-AD model mice to elucidate the molecular pathological changes from the early to end stages of Alzheimer's disease (AD). OBJECTIVE: We re-analyzed our previously published microarray data obtained from the hippocampus of 3xTg-AD model mice at 12 and 52 weeks of age. METHODS: Functional annotation and network analyses of the up- and downregulated differentially expressed genes (DEGs) in mice aged 12 to 52 weeks were performed. Validation tests for gamma-aminobutyric acid (GABA)-related genes were also performed by quantitative polymerase chain reaction (qPCR). RESULTS: In total, 644 DEGs were upregulated and 624 DEGs were downregulated in the hippocampus of both the 12- and 52-week-old 3xTg-AD mice. In the functional analysis of the upregulated DEGs, 330 gene ontology biological process terms, including immune response, were found, and they interacted with each other in the network analysis. In the functional analysis of the downregulated DEGs, 90 biological process terms, including several terms related to membrane potential and synapse function, were found, and they also interacted with each other in the network analysis. In the qPCR validation test, significant downregulation was seen for Gabrg3 at the ages of 12 (p = 0.02) and 36 (p = 0.005) weeks, Gabbr1 at the age of 52 weeks (p = 0.001), and Gabrr2 at the age of 36 weeks (p = 0.02). CONCLUSION: Changes in immune response and GABAergic neurotransmission may occur in the brain of 3xTg mice from the early to end stages of AD.

DOI： 10.3233/JAD-230078

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担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The onset of schizophrenia is associated with both genetic and environmental risks during brain development. Environmental factors during pregnancy can represent risk factors for schizophrenia, and we have previously reported that several microRNA and mRNA expression changes in fetal brains exposed to haloperidol during pregnancy may be related to the onset of this disease. This study aimed to replicate that research and focused on apoptotic-related gene expression changes. METHODS: Haloperidol (1mg/kg) or aripiprazole (1mg/kg) was injected into pregnant mice. Using RNA sequencing for the hippocampus of each offspring born from pregnant mice exposed to haloperidol, we analyzed genes identified as changed in our previous report and validated two apoptosis-related genes (Cdkn1a and Apaf1) using quantitative polymerase chain reaction (qPCR) methods. Furthermore, we attempted to elucidate the direct effects of haloperidol and aripiprazole on those mRNA expressions in in vitro experiments. RESULTS: RNA sequencing successfully replicated 16 up-regulated and 5 down-regulated genes in this study. Of those, up-regulations of Cdkn1a and Apaf1 mRNA expression were successfully validated by direct quantification. Moreover, haloperidol and aripiprazole dose-dependent upregulation of both mRNA expressions were confirmed in a Neuro2a cell line. CONCLUSIONS: In the hippocampus of offspring, intraperitoneal injection of haloperidol to pregnant mice induced up-regulation of apoptotic genes that representing the phenotypic change without apoptosis. These findings will be useful for understanding the molecular biological mechanisms underlying the effects of antipsychotics on the fetal brain.

DOI： 10.1016/j.brainresbull.2023.110662

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担当区分：責任著者   掲載種別：研究論文（学術雑誌）  

DOI： 10.3390/brainsci13010027

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Senile depression (SD) is a heterogeneous syndrome. Several clinical profiles are more likely to appear in SD than in early-life depression, but it remains unclear whether the pathophysiology is different. The prevalence of dementia increases with aging, and the underlying pathophysiological processes in the preclinical phase begin even before cognitive deficits or neurological signs appear. SD may be either a risk factor for developing dementia or a prodromal stage of dementia. The inconsistent findings regarding the association between SD and incident dementia may be attributable to the neuropathological heterogeneity underlying SD. Most studies have focused on patients with the clinical diagnosis of Alzheimer disease (AD) as an outcome, but several clinicopathological studies suggest that primary age-related tauopathy and argyrophilic grain disease may account for a proportion of cases clinically misdiagnosed as AD in the elderly population. Furthermore, most AD cases have additional neuropathologic changes such as cerebrovascular disease and Lewy body disease. Here, we review the neuropathological findings linking SD to incident dementia, focusing on common age-related neuropathologies. In particular, the roles of disturbance of neural circuity, imbalance of monoaminergic systems, dysregulation of the hypothalamic-pituitary-adrenal axis, and elevated neuroinflammatory status are discussed. Finally, we review the current treatment of SD in the context of age-related neuropathological changes.

DOI： 10.1111/pcn.13485

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media {LLC}  

Alzheimer's disease (AD) is a progressive disease, and the number of AD patients is increasing every year as the population ages. One of the pathophysiological mechanisms of AD is thought to be the effect of metabolomic abnormalities. There have been several studies of metabolomic abnormalities of AD, and new biomarkers are being investigated. Metabolomic studies have been attracting attention, and the aim of this study was to identify metabolomic biomarkers associated with AD and mild cognitive impairment (MCI). Of the 927 participants in the Nakayama Study conducted in Iyo City, Ehime Prefecture, 106 were selected for this study as Control (n = 40), MCI (n = 26), and AD (n = 40) groups, matched by age and sex. Metabolomic comparisons were made across the three groups. Then, correlations between metabolites and clinical symptoms were examined. The blood mRNA levels of the ornithine metabolic enzymes were also measured. Of the plasma metabolites, significant differences were found in ornithine, uracil, and lysine. Ornithine was significantly decreased in the AD group compared to the Control and MCI groups (Control vs. AD: 97.2 vs. 77.4; P = 0.01, MCI vs. AD: 92.5 vs. 77.4; P = 0.02). Uracil and lysine were also significantly decreased in the AD group compared to the Control group (uracil, Control vs. AD: 272 vs. 235; P = 0.04, lysine, Control vs. AD: 208 vs. 176; P = 0.03). In the total sample, the MMSE score was significantly correlated with lysine, ornithine, thymine, and uracil. The Barthel index score was significantly correlated with lysine. The instrumental activities of daily living (IADL) score were significantly correlated with lysine, betaine, creatine, and thymine. In the ornithine metabolism pathway, the spermine synthase mRNA level was significantly decreased in AD. Ornithine was decreased, and mRNA expressions related to its metabolism were changed in the AD group compared to the Control and MCI groups, suggesting an association between abnormal ornithine metabolism and AD. Increased betaine and decreased methionine may also have the potential to serve as markers of higher IADL in elderly persons. Plasma metabolites may be useful for predicting the progression of AD.

DOI： 10.1038/s41598-022-19670-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: Recently, the expression changes of microRNAs (miRNAs) in the serum exosomes (EXO) of schizophrenia (SCZ) have been reported. The aim of this study was to investigate the global expression changes of miRNA derived from the plasma EXO of patients with treatment-resistant schizophrenia (TRS) and the effects of clozapine on miRNA expression. METHODS: Global miRNA expression changes in plasma EXO between TRS and controls were studied using microarray analysis. Then, miRNA expressions among TRS, non-TRS, and controls were confirmed with quantitative qPCR experiments. We also studied changes in EXO miRNA expression with in-vitro SH-SY5Y cells. RESULTS: A microarray for miRNA expression analysis (nine controls vs. nine patients with TRS) revealed 13 up- and 18 downregulated miRNAs that were relevant to neuronal and brain development based on gene ontology analysis. Of those, upregulated miR-675-3p expression was successfully validated in the same cohort by qPCR experiments. Conversely, miR-675-3p expression levels were significantly decreased in the non-TRS cohort (50 controls vs. 50 patients without TRS without clozapine treatment). CONCLUSIONS: We identified global miRNA changes in plasma EXO derived from patients with SCZ that were relevant to neuronal functions, among which, hsa-miR-675-3p expression was upregulated by clozapine treatment.

DOI： 10.1080/15622975.2022.2104924

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Schizophrenia is a mental disorder caused by both environmental and genetic factors. Prenatal exposure to antipsychotics, an environmental factor for the fetal brain, induces apoptotic neurodegeneration and cognitive impairment of offspring similar to schizophrenia. The aim was to investigate molecular biological changes in the fetal hippocampus exposed to haloperidol (HAL) by RNA expression as a model of the disorder. METHODS: HAL (1 mg/kg/day) was administered to pregnant mice. Upregulated and downregulated gene expressions in the hippocampus of offspring were studied with RNA-seq and validated with the qPCR method, and miRNA regulating mRNA expressional changes was predicted by in silico analysis. An in vitro experiment was used to identify the miRNA using a dual-luciferase assay. RESULTS: There were significant gene expressional changes (1,370 upregulated and 1,260 down regulated genes) in the HAL group compared to the control group on RNA-seq analysis (p < 0.05 and q < 0.05). Of them, the increase of Nr3c1 mRNA expression was successfully validated, and in silico analysis predicted that microRNA-137-3p (miR-137-3p) possibly regulates that gene's expression. The expression of miR-137-3p in the hippocampus of offspring was significantly decreased in the first generation, but it increased in the second generation. In vitro experiments with Neuro2a cells showed that miR-137-3p inversely regulated Nr3c1 mRNA expression, which was upregulated in the HAL group. CONCLUSIONS: These findings will be keys for understanding the impact of the molecular biological effects of antipsychotics on the fetal brain.

DOI： 10.1093/ijnp/pyac044

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Late-onset Alzheimer's disease (LOAD) is a complex disease in which neuroinflammation plays an important pathophysiological role, and exposure to neurotoxic substrates such as aldehydes may contribute. Blood mRNA expression levels of neuroinflammation-related genes appear to be potential biological markers of LOAD. A relationship between ALDH2 and LOAD has been suggested. OBJECTIVE: Our objective was to examine blood ALDH2 expression in Japanese LOAD patients, conduct a genetic association study, and add new studies to an extended meta-analysis of the Asian population. METHODS: A blood expression study (45 AD subjects, 54 controls) in which total RNA was isolated from whole peripheral blood samples and ALDH2 expression measured was conducted. In addition, a genetic association study (271 AD subjects, 492 controls) using genomic DNA from whole peripheral blood samples was conducted. Finally, a meta-analysis examined the relationship between ALDH2*2 frequency and the risk of LOAD. RESULTS: ALDH2 mRNA expression was significantly higher in LOAD than in controls, and also higher in men with LOAD than in women with LOAD (p = 0.043). The genotypes in the two classified groups and the allele frequency were significantly different between AD and control subjects. The meta-analysis showed a significant difference in the ALDH2*2 allele, with an increased AD risk (OR = 1.38; 95% CI = 1.02-1.85; p = 0.0348, I2 = 81.1%). CONCLUSION: There was a significant increase in blood ALDH2 expression, and a genetic association with ALDH2*2 in LOAD. ALDH2 may have significant roles in the pathogenesis of LOAD in the Asian population.

DOI： 10.3233/JAD-215627

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Objective: To investigate the efficacy of tandospirone, an azapirone anxiolytic similar to buspirone that is used in Japan, for behavioral and psychological symptoms of dementia (BPSD), especially in oldest-old patients. Methods: This was an open-label observational study involving residents with BPSD in a special elderly nursing home between August 2013 and August 2018. The severity of dementia was assessed using the Clinical Dementia Rating (CDR) scale; as the main outcomes, the severity of BPSD was assessed using the Clinical Global Impressions-Severity scale (CGI-S) and Neuropsychiatric Inventory-12 (NPI-12) at baseline and 4 weeks after the maintenance dose of tandospirone was reached. The administration of tandospirone started at 30 mg, divided into three doses per day. Two weeks later, if the efficacy was sufficient based on the clinical nursing record, that dose was continued; if the efficacy was insufficient, the daily dose was increased from 40 mg/day to a maximum dose of 60 mg/day. Results: Thirty-three participants (25 females [76%], mean age 87.1 ± 5.4 years) completed the study. Twenty-three participants (70%) were oldest-old (18 females [78%], mean age 89.9 ± 3.4 years). The mean CDR score was 2.9 ± 0.3 in all participants. Tandospirone treatment showed few or no obvious adverse effects and significantly improved CGI-S scores, as well as total scores and many subscale scores on the NPI-12, in both the sample at large and the oldest-old participants. Conclusion: This study demonstrated the efficacy and safety of tandospirone for BPSD in oldest-old participants.

DOI： 10.9758/cpn.2021.19.3.514

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Autism spectrum disorder (ASD) is characterized as a neurodevelopmental disorder, and one of the main hypotheses regarding its cause is genetic factors. A previous meta-analysis of seven microarray studies and one RNA sequencing (RNA-seq) study using the blood of children with ASD identified dysregulation of gene expressions relevant to the immune system. In this study, we explored changes in global gene expression as the phenotype of ASD in the blood of adults with ASD. METHODS: We recruited an RNA-seq cohort (ASD vs. control; n = 6 each) and a replication cohort (ASD vs. control; n = 19 each) and conducted RNA-seq to explore changes in global gene expression. We then subjected the significantly up- and downregulated genes to gene ontology (GO) and core analyses. Weighted gene correlation network analysis (WGCNA) was performed with all 11,617 genes detected in RNA-seq to identify the ASD-specific gene network. RESULTS: In total, 117 significantly up- and 83 significantly downregulated genes were detected in the ASD compared with the control group, respectively (p < 0.05 and q < 0.05). GO analysis revealed that the aberrant innate and adaptive immunity were more obvious in the 117 upregulated than in the 83 downregulated genes. WGCNA with core analysis revealed that one module including many immune-related genes was associated with the natural killer cell signaling pathway. In the results for the replication cohort, significant changes with same trend found in RNA-seq data were confirmed for MAFB (p = 0.046), RPSAP58 (p = 0.030), and G2MK (p = 0.004). LIMITATIONS: The sample size was relatively small in both the RNA-seq and replication cohorts. This study examined the mRNA expression level, so the interaction between mRNA and protein remains unclear. The expression changes between children and adults with ASD were not compared because only adults with ASD were targeted. CONCLUSIONS: The dysregulated gene expressions confirmed in the blood of adults with ASD were relevant to the dysfunction of innate and adaptive immunity. These findings may aid in understanding the pathogenesis of ASD.

DOI： 10.1186/s12974-021-02154-7

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Alanine:glyoxylate aminotransferase 2 (AGXT2; EC 2.6.1.44) is the only enzyme that degrades the R-form of 3-aminoisobutyrate, an intermediate metabolite of thymine. AGXT2, as well as diaminoarginine dimethylaminohydrolase 1 (DDAH1; EC 3.5.3.18), works as an enzyme that degrades asymmetric dimethylarginine (ADMA), which competitively inhibits the nitric oxide synthase family. Thus, these two enzyme activities may change vascular vulnerability for a lifetime via the nitric oxide (NO) system. We investigated the association between vascular conditions and diseases such as hypertension and diabetes mellitus and polymorphisms of these two genes in 750 older Japanese subjects (mean age ± standard deviation, 77.0 ± 7.6 years) recruited using the complete enumeration survey method in the Nakayama study. Demographic and biochemical data, such as blood pressure (BP) and casual blood sugar (CBS), were obtained. Four functional single nucleotide polymorphisms (SNPs; rs37370, rs37369, rs180749, and rs16899974) of AGXT2 and one functional insertion/deletion polymorphism in the promotor region with four SNPs (rs307894, rs669173, rs997251, and rs13373844) of DDAH1 were investigated. Plasma ADMA was also analyzed in 163 subjects. RESULTS: The results of multiple regression analysis showed that a loss of the functional haplotype of AGXT2, CAAA, was significantly positively correlated with BP (systolic BP, p = 0.034; diastolic BP, p = 0.025) and CBS (p = 0.021). No correlation was observed between DDAH1 and either BP or CBS. ADMA concentrations were significantly elevated in subjects with two CAAA haplotypes compared with subjects without the CAAA haplotype (p = 0.033). CONCLUSIONS: Missense variants of AGXT2, but not DDAH1, may be related to vulnerability to vascular diseases such as hypertension and DM via the NO system.

DOI： 10.1186/s12864-021-07612-3

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The pathophysiology of delayed carbon monoxide (CO) encephalopathy remains unclear. In this study, the effects of CO exposure on the dentate gyrus (DG) were investigated in a Wistar rat model by histochemical and molecular methods. Model rats showed significant cognitive impairment in the passive-avoidance test beginning 7 days after CO exposure. Immunohistochemistry showed that compared to the control, the cell number of SRY (sex-determining region Y)-box 2 (SOX2)+/brain lipid binding protein (BLBP)+/glial fibrillary acidic protein (GFAP)+ cells in the DG was significantly less, but the number of SOX2+/GFAP- cells was not, reflecting a decreased number of type 1 and type 2a neural precursor cells. Compared to the control, the numbers of CD11b+ cells and neuron glial antigen 2+ cells were significantly less, but the number of SOX2-/GFAP+ cells was not. Flow cytometry showed that the percent of live microglial cells isolated from the hippocampus in this CO rat model was significantly lower than in controls. Furthermore, mRNA expression of fibroblast growth factor 2 and glial cell-derived neurotrophic factor, which are neurogenic factors, was significantly decreased in that area. We conclude that, in this rat model, there is an association between delayed cognitive impairment with dysregulated adult hippocampal neurogenesis and glial changes in delayed CO encephalopathy.

DOI： 10.1038/s41598-021-85860-9

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担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Cyclin-dependent kinase inhibitor 2A (CDKN2A) is an important gene in cellular senescence and aging. OBJECTIVE: This study assessed the utility of blood CDKN2A mRNA expression levels and methylation status as a potential biomarker for aging and the pathogenesis of Alzheimer's disease (AD). METHODS: The correlation between CDKN2A mRNA expression levels and age was examined in 45 healthy subjects, after which mRNA expression levels were compared among 46 AD patients, 20 mild cognitive impairment due to AD patients, 21 Parkinson's disease patients, 21 dementia with Lewy bodies patients, and 55 older healthy controls. The methylation rates of the second exon of the CDKN2A gene, known to influence its expression levels, was also examined. RESULTS: A significant correlation between CDKN2A mRNA expression levels and age was found (Spearman's rank correlation coefficient: r = 0.407, p = 0.005). CDKN2A mRNA expression levels in blood were significantly decreased in AD patients, although those of healthy controls were significantly increased with age. Further, only in AD patients were CDKN2A mRNA expression levels significantly and positively correlated with methylation rates. CONCLUSION: Although further research with a larger sample size is needed to elucidate the relationships between CDKN2A gene expression in blood and the development of other neurodegenerative diseases, CDKN2A mRNA expression in blood may be a biomarker for differentiating AD from normal aging and other neurodegenerative diseases.

DOI： 10.3233/JAD-210483

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：{IOS} Press  

BACKGROUND: Phosphatidylinositol-binding clathrin assembly protein (PICALM) is a validated genetic risk factor for late-onset Alzheimer's disease (AD) and is associated with other neurodegenerative diseases. However, PICALM expression in the blood of neurodegenerative diseases remains elusive. OBJECTIVE: This study aimed to assess the usefulness of PICALM expression levels in the blood of patients with AD, Parkinson's disease (PD), dementia with Lewy bodies (DLB), and geriatric major depressive disorder (MDD) as a diagnostic biomarker. METHODS: In total, 45, 20, 21, and 19 patients with AD, PD, DLB, and geriatric MDD, respectively, and 54 healthy controls (HCs) were enrolled in the study. Expression data from Gene Expression Omnibus database (GSE97760), (GSE133347) and (GSE98793), (GSE48350), and (GSE144459) were used to validate the ability of biomarkers in the blood of patients with AD, PD, geriatric MDD, and a postmortem human AD brain and animal model of AD (3xTg-AD mouse), respectively. RESULTS: PICALM mRNA expression in human blood was significantly increased in patients with AD compared with that in HCs. PICALM mRNA expression and age were negatively correlated only in patients with AD. PICALM mRNA expression in human blood was significantly lower in patients with PD than in HCs. No changes in PICALM mRNA expression were found in patients with DLB and geriatric MDD. CONCLUSION: PICALM mRNA expression in blood was higher in patients with AD, but lower in patients with PD, which suggests that PICALM mRNA expression in human blood may be a useful biomarker for differentiating neurodegenerative diseases and geriatric MDD.

DOI： 10.3233/JAD-201046

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media {LLC}  

The testing of pathological biomarkers of Alzheimer's disease (AD), such as amyloid beta and tau, is time-consuming, expensive, and invasive. Here, we used 3xTg-AD mice to identify and validate putative novel blood transcriptome biomarkers of AD that can potentially be identified in the blood of patients. mRNA was extracted from the blood and hippocampus of 3xTg-AD and control mice at different ages and used for microarray analysis. Network and functional analyses revealed that the differentially expressed genes between AD and control mice modulated the immune and neuroinflammation systems. Five novel gene transcripts (Cdkn2a, Apobec3, Magi2, Parp3, and Cass4) showed significant increases with age, and their expression in the blood was collated with that in the hippocampus only in AD mice. We further assessed previously identified candidate biomarker genes. The expression of Trem1 and Trem2 in both the blood and brain was significantly increased with age. Decreased Tomm40 and increased Pink1 mRNA levels were observed in the mouse blood. The changes in the expression of Snca and Apoe mRNA in the mouse blood and brain were similar to those found in human AD blood. Our results demonstrated that the immune and neuroinflammatory system is involved in the pathophysiologies of aging and AD and that the blood transcriptome might be useful as a biomarker of AD.

DOI： 10.1007/s12035-020-02058-2

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: We recently reported that older patients with schizophrenia (SZ) show possible idiopathic normal pressure hydrocephalus (iNPH) more frequently than the general population. In this study, we estimated the prevalence of iNPH in a larger number of older SZ patients and explored useful examination values for diagnosis in the SZ population. METHODS: We enrolled older inpatients with SZ (n = 39, mean age = 68.6 ± 7.7 years) from several psychiatric hospitals in Ehime, Japan and acquired brain imaging data using computed tomography. We evaluated three iNPH symptoms (dementia, gait disturbance, and urinary incontinence). In addition, we combined these data with our previous data to elucidate the relationship between iNPH and characteristics of SZ symptoms. RESULTS: In total, five (12.8%) patients were diagnosed with possible iNPH. Evans' index for patients with iNPH was significantly higher than for those without iNPH (p = 0.002). The number of disproportionately enlarged subarachnoid space hydrocephalus (DESH) findings was significantly higher in patients with iNPH than in those without iNPH (p <  0.001). Using combined data, Drug-Induced Extra-pyramidal Symptoms Scale (DIEPSS) subscales of gait and bradykinesia showed an increasing trend in the SZ with iNPH group. CONCLUSIONS: We reconfirmed that older inpatients with SZ experienced possible iNPH more frequently than the general population. We should pay attention to the DIEPSS subscales of gait and bradykinesia and DESH findings in addition to the three main symptoms of iNPH and Evans' index so as to not miss SZ patients with iNPH.

DOI： 10.1186/s12888-020-02690-1

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

CTL-associated antigen 4 (CTLA4) and its downstream signals compose an important mechanism that suppresses immune activity. Recent studies have shown that immune abnormalities are associated with the pathogenesis of schizophrenia (SCZ), but little research has been performed on the relevance of CTLA4 and SCZ. In the present study, we investigated the relationship between CTLA4 mRNA expression and SCZ. We examined the expression of CTLA4 mRNA in blood from patients with SCZ, bipolar disorder (BD), and major depressive disorder (MDD). We compared 50 SCZ subjects, 46 BD subjects, and 63 MDD subjects with age- and sex-matched healthy controls (HCs). Quantitative real-time PCR was performed to examine CTLA4 mRNA expression in peripheral blood using TaqMan probes. Levels of CTLA4 mRNA expression were significantly lower in patients with SCZ compared with HCs (p < 0.001), whereas no differences were found between affective disorder (BD and MDD) patients and HCs. We analyzed the correlation between CTLA4 mRNA expression and clinical parameters, but no significant correlation was found. The expression of CTLA4 mRNA was lower specifically in SCZ, suggesting that abnormal CTLA4 expression may be particularly related to the pathogenesis of SCZ. CTLA4 may be a useful diagnostic marker and a potential therapeutic target of SCZ.

DOI： 10.1016/j.ajp.2020.102112

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

OBJECTIVE: The aim was to clarify whether DRD2 methylation changes in leukocytes of dementia with Lewy bodies (DLB) or Parkinson's disease (PD) patients are seen and can be used to discriminate between them. METHODS: Methylation rates were examined in 23 DLB subjects and 23 age- and sex-matched healthy controls and 37 PD patients and 37 age- and sex-matched healthy controls. RESULTS: Significant DRD2 DNA methylation changes were found in leukocytes of DLB and PD patients compared with healthy subjects. Discriminant analysis between DLB and PD using seven CpG sites demonstrated sensitivity and specificity of 83.8% and 90.9%, respectively. None of the CpG sites were associated with sex, age, age of onset, disease duration, and any of the neuropsychological tests in DLB and PD patients. CONCLUSION: This is the first report showing that DRD2 DNA methylation rates in leukocytes were increased in DLB patients and decreased in PD patients. These results may be an important step in understanding epigenetic mechanisms underlying DLB and PD pathogenesis and providing a novel biomarker for discriminating between them.

DOI： 10.1111/ane.13186

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Introduction: Although ATP-binding cassette sub-family A member 7 gene (ABCA7) is known to be associated with Alzheimer's disease, the relationship between ABCA7 and schizophrenia has been unknown. Methods: Schizophrenia patients (n = 50; 24 males, 62.1 ± 0.50 years old) and age- and sex-matched healthy controls (n = 50) were recruited for the mRNA analysis. Additionally, a case-control study for the rs3764650 genotypes was performed with 1308 samples (control subjects; n = 527, schizophrenia patients; n = 781). All participants were Japanese, unrelated to each other, and living in the same area. Results: The distributions of the rs3764650 genotypes in schizophrenia patients were not different from that of controls. However, the ABCA7 mRNA expression levels in schizophrenia patients were significantly higher than those in controls by a logistic regression analysis. Additionally, the ABCA7 mRNA expression levels in schizophrenia patients were correlated with the rs3764650 genotypes in a dose-dependent manner. Discussion: The ABCA7 mRNA expression levels in peripheral blood with the rs3764650 genotypes may be related to pathological mechanisms in schizophrenia and may be a biological marker for schizophrenia.

DOI： 10.2147/NDT.S238471

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The gene for dopamine receptor D2 (DRD2) is associated with schizophrenia (SCZ). Epigenetic changes may be related to SCZ pathology. The -141C Ins/Del polymorphism in DRD2 (rs1799732) is functional and associated with SCZ. Fifty SCZ patients and 50 control subjects were newly recruited and analyzed in addition to 50 previously reported SCZ samples and 50 previously reported control samples. Genomic DNA from peripheral leukocytes was analyzed. We replicated analysis of DNA methylation rates at seven CpG sites (CpG 1-1 to 1-7) and also analyzed five additional sites (CpG 2-1 to 2-5) in the upstream region of DRD2. We also performed genotyping of -141C IIns/Del and analyzed the effects of -141C Ins/Del on methylation of DRD2. Methylation rates were significantly lower in SCZ patients compared to control subjects, respectively. In control subjects, the methylation rates were significantly lower in individuals with the Ins/Ins genotype than in Del allele carriers. We replicated hypomethylation of the DRD2 promoter region in SCZ patients compared to age-matched control subjects. The -141C Ins/Del polymorphism affected the methylation rates in regions of DRD2. Hypomethylation and the -141C Ins/Del polymorphism of DRD2 may be biomarkers for SCZ.

DOI： 10.1016/j.psychres.2019.06.001

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: Ghrelin regulates appetite and also plays important roles in cognition and may be involved in vulnerability to SCZ. METHODS: In this study, we measured mRNA expression of the ghrelin-related molecules, growth hormone secretagogue receptor 1a (GHS-R1a) and 1b (GHS-R1b), and the ghrelin activator, membrane bound O-acyltransferase 4 (MBOAT4). Peripheral leukocytes from Japanese patients with SCZ (n = 49; 23 males, 26 females; age = 61.8 ± 13.3 years) and controls (n = 50; 25 males, 25 females; age = 62.0 ± 14.3 years) were recruited according to their clinical information. We also studied the DNA methylation rates of these genes in DNA from leukocytes. RESULTS: The mRNA expression of GHS-R1a was significantly decreased in SCZ (SCZ vs. control: 0.35 ± 0.081 vs. 1.00 ± 0.059, respectively, p = 0.007), but expression levels of GHS-R1b and MBOAT4 were significantly increased in SCZ (SCZ vs. control: 2.02 ± 0.91 vs. 1.00 ± 0.32, p = 0.023, 1.37 ± 0.21 vs. 1.00 ± 0.11, respectively, p = 0.014). No differences in methylation rates for any genes were found. CONCLUSION: We conclude that opposite expression of GHS-R1a and GHS-R1b, and elevated MBOAT4 mRNA expression may reflect the mechanisms of SCZ.

DOI： 10.1016/j.psychres.2018.12.135

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The neuroprotective effect of ghrelin has recently been reported in Alzheimer's disease (AD). Ghrelin is converted from des-acyl ghrelin to the activated form, acyl ghrelin, by membrane bound o-acyltransferase 4 (MBOAT4), and then binds to growth hormone secretagogue receptor (GHS-R). We examined the levels of plasma acyl/des-acyl ghrelin in 75 AD subjects and age- and sex-matched controls, as well as the DNA methylation and mRNA expression of MBOAT4 and GHS-R in peripheral leukocytes. The acyl ghrelin concentration was significantly higher in AD subjects than in controls (2.18 ± 1.25 vs. 1.49 ± 2.3, p = 0.001). The methylation rate of MBOAT4 CpG 2 was significantly lower in AD subjects than in controls (4.0 ± 0.9 vs. 4.7 ± 1.2, p < 0.001). The mRNA expression levels of MBOAT4 and GHS-R1b were significantly higher in AD subjects than in controls (MBOAT4: 1.10 ± 0.48 vs. 1.0 ± 0.55, p = 0.049; GHS-R1b: 1.76 ± 3.18 vs. 1.0 ± 1.56, p = 0.030). These changes in the ghrelin cascade in peripheral blood may reflect those in the brain, and may be a neuroprotective biomarker in AD.

DOI： 10.1016/j.jpsychires.2018.10.011

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その他リンク： http://orcid.org/0000-0003-4409-3096

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Triggering receptor expressed on myeloid cells 2 (TREM2) activates the innate immune system, promotes phagocytosis by microglia, and is associated with Alzheimer's disease (AD). The possible role of a related molecule, TREM1, in AD remains unknown. OBJECTIVE: We investigated a possible role for TREM1 in AD by determining the gene expression and methylation levels of TREM1 in leukocytes from AD patients. METHODS: Fifty patients with AD and 50 age-matched healthy controls were enrolled. AD patients underwent a battery of neuropsychiatric tests. Peripheral blood samples were obtained from each participant, RNA and DNA were extracted, and samples were assessed for TREM1 mRNA expression and methylation rates at three CpG sites in the TREM1 promoter. RESULTS: TREM1 mRNA expression levels in AD patients were significantly higher than those in controls (p = 0.008). TREM1 mRNA expression levels were not correlated with sex, age, duration of illness, APOE genotype, donepezil treatment, or scores of most neuropsychiatric tests. TREM1 mRNA expression levels in AD patients were correlated with the total score of the Montgomery-Åsberg Depression Rating Scale (p = 0.047, r = - 0.344). Methylation rates at the three CpG sites were significantly lower in AD patients than in controls. We also found a significant correlation between TREM1 mRNA expression and TREM1 DNA methylation rates (p < 0.001). CONCLUSION: TREM1 may be associated with the immune responses in AD, and along with hypomethylation at CpG sites in the TREM1 promoter, may become part of a biomarker panel for AD pathogenesis.

DOI： 10.3233/jad-180418

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Blackwell Publishing  

AIM: Despite continuing research into Alzheimer's disease (AD), its pathological mechanisms and modulating factors remain unknown. Several genes influence AD pathogenesis by affecting inflammatory pathways. Myocyte-enhancer factor 2C (MEF2C) is one such candidate gene for AD. METHODS: We examined MEF2C mRNA expression levels and methylation rates of CpG on its promoter region in peripheral leukocytes from Japanese AD patients compared with age- and sex-matched control subjects. RESULTS: In peripheral leukocytes, MEF2C mRNA expression levels in AD subjects were significantly lower than those in control subjects (0.86 ± 0.25 vs 0.99 ± 0.27, respectively, P = 0.007) and were correlated with the Alzheimer's Disease Assessment Scale (r = -0.345, P = 0.049) and the Mini Mental State Examination (r = 0.324, P = 0.02). No significant differences were found in methylation rates between AD and control subjects. CONCLUSION: MEF2C mRNA expression in leukocytes may be a biological marker for cognitive decline in AD.

DOI： 10.1111/pcn.12618

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

OBJECTIVES: Recent genome-wide association studies revealed that Triggering receptor expressed on myeloid cells 2 (TREM2) was associated with Alzheimer's disease (AD) and other neurodegenerative diseases. We previously reported that TREM2 mRNA is highly expressed in leukocytes of AD patients compared to those in healthy controls. However, the mechanism of TREM2 expression change is still not known. In this study, we examined the involvement of the DNA methylation status of TREM2 in its high gene expression. MATERIALS AND METHODS: Fifty AD subjects and age- and sex-matched control subjects were recruited (25 males, 25 females; 79.9 ± 5.27 and 79.4 ± 3.92 years old, respectively). TREM2 mRNA expression and the percentage of DNA methylation at four CpG sites in intron 1 of TREM2 were studied using their peripheral leukocytes. RESULTS: We confirmed that TREM2 mRNA expression in leukocytes was significantly higher in AD patients than in controls (p = 0.007). The percentage methylation at three CpG sites in TREM2 intron 1 was significantly lower in AD subjects than in control: CpG1, 9.4 ± 3.2 vs 11.9 ± 4.0 (p = 0.001); CpG2, 15.4 ± 4.9 vs 19.1 ± 4.8 (p = 0.001); CpG3, 20.8 ± 5.5 vs 25.5 ± 5.4 (p < 0.001); and the average percentage methylation of all CpG sites: 13.5 ± 3.7 vs 16.1 ± 3.8 (p = 0.002), respectively. In addition, there were significant negative correlations between TREM2 mRNA expression and the percentage DNA methylation of each of CpG sites (CpG1, r = -0.416, p < 0.001; CpG2, r = -0.510, p < 0.001; CpG3, r = -0.504, p < 0.001; CpG4, r = -0.356, p < 0.001). CONCLUSIONS: Lower DNA methylation at TREM2 intron 1 caused higher TREM2 mRNA expression in the leukocytes of AD subjects versus controls and may be a biomarker for AD.

DOI： 10.1016/j.jpsychires.2017.04.003

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

BACKGROUND: Nitric oxide (NO) is a neurotransmitter that may be related to major depressive disorder (MDD) because the selective neuronal NO synthase (NOS) inhibitor, 7-nitroindazole, induces a dose-dependent antidepressant-like effect. NO modulates major neurotransmitters involved in the neurobiology of MDD, such as norepinephrine, serotonin, dopamine, and glutamate. In this study, we investigated the effects of antidepressants as NO modulators in acute and sub-chronic treatments. METHODS: Rats were injected with the SSRI paroxetine (PAR, 10 mg/kg), the SNRI milnacipran (MIL, 30 mg/kg), or the NaSSA mirtazapine (MIR, 10 mg/kg) for acute (1 h) or sub-chronic (3 weeks) treatment prior to analysis of nine brain regions (frontal cortex, temporal cortex, striatum, thalamus, hippocampus, midbrain, pons, cerebellum, and olfactory bulb). The mRNA expression levels of three NOS subtypes (neuronal: nNOS, inducible: iNOS, and endothelial: eNOS) were analyzed using real-time PCR with Taqman probes. RESULTS: Acute MIR treatment significantly increased nNOS mRNA expression in the hippocampus, midbrain, cerebellum and olfactory bulb, and iNOS mRNA expression in the frontal cortex and midbrain. Acute PAR and MIR treatments significantly increased eNOS mRNA expression in most brain regions. Conversely, sub-chronic treatment with all types of antidepressants resulted in significant decreases of eNOS mRNA expression in most brain regions. CONCLUSIONS: Sub-chronic treatment with the three types of antidepressants consistently decreased eNOS mRNA expression levels in the rat brain. These effects may be associated with the involvement of the NO system in the mechanism of action of antidepressants.

DOI： 10.1007/s00213-017-4567-z

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：FRONTIERS MEDIA SA  

A hypothesis for schizophrenia (SCZ) called the microglia hypothesis has been suggested. In SCZ, expression of triggering receptor expressed on myeloid cell 2 (TREM2) mRNA is higher in leukocytes than in healthy individuals. Here, the methylation rates of four CpG sites in TREM2 intron 1 that may bind important transcription factors and the correlation between the methylation rate and mRNA expression were determined. We compared the methylation rates in SCZ patients and age-matched controls (n = 50 each). SCZ patients had significantly lower methylation rates of CpG 2 (17.0 +/- 6.7 vs. 20.2 +/- 5.0; p = 0.02) and CpG 3 (23.8 +/- 8.2 vs. 28.1 +/- 6.2; p = 0.01). The average methylation rate (15.3 +/- 5.2 vs. 17.6 +/- 3.9; p = 0.009) was also lower. A significant negative correlation was found between TREM2 mRNA expression and the methylation rate of CpG 2 (r = -0.252, p = 0.012). SCZ susceptibility markers may include low methylation at TREM2 intron 1 and increased TREM2 mRNA levels. Our pilot study requires validation with higher numbers of participants and with other myeloid cell types.

DOI： 10.3389/fnins.2017.00275

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：TAYLOR & FRANCIS LTD  

BACKGROUND: Recently, it was reported that antipsychotic treatment reverted Contactin Associated Protein-Like 3 (CASPR3, same as CNTNAP3) mRNA expressions in leukocytes of schizophrenia (SCZ) subjects to the same levels as healthy controls. CASPR3 was expressed in various regions of the mice brain (cortex, frontal lobes, corpus callosum, hippocampus, etc.). Thus, this study evaluated CASPR3 mRNA expression in SCZ subjects to find a new clue of schizophrenia pathogenesis. METHODS: One hundred SCZ subjects and 100 age-matched controls were compared. Levels of CASPR3 mRNA in leukocytes were analysed with a quantitative real-time PCR method using TaqMan probes. RESULTS: CASPR3 mRNA expression was significantly higher in leukocytes of SCZ subjects than controls. However, there were no significant correlations between expression level and any clinical parameters in 50 SCZ subjects. CONCLUSION: Considering that CASPR3 is involved in building the brain neural network and autophagy in circulating leukocytes, abnormal CASPR3 expression in SCZ subjects may be associated with the pathogenesis of SCZ.

DOI： 10.1080/08039488.2017.1291720

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

AimIt is difficult to diagnose dementia with Lewy bodies (DLB) because it exhibits clinical and neuropathological overlap with both Alzheimer's disease and Parkinson's disease. The -synuclein protein is a major component of Lewy bodies, and accumulation of -synuclein aggregates causes synaptic dysfunction in DLB. Epigenetic changes at the synuclein alpha (SNCA) gene may be involved in DLB pathogenesis.
MethodsWe examined DNA methylation rates at 10 CpG sites located in intron 1 of SNCA and SNCA mRNA expression in peripheral leukocytes to compare DLB patients (n=20; nine men, 11 women; age=78.87.7years) with healthy controls (n=20; eight men, 12 women; age=77.0 6.9years).
ResultsThe methylation rate at CpG 4 (P=0.002) and the overall mean methylation rate at these sites (P&lt; 0.001) were significantly lower in DLB patients than in healthy controls after Bonferroni correction. Although SNCA126, a partial form of SNCA mRNA expression, was significantly increased in DLB (P=0.017), there was no significant difference in total SNCA mRNA expression between DLB patients and healthy controls (P=0.165). No correlation was observed between SCNA mRNA expression levels and blood DNA methylation rates in either DLB or healthy controls.
ConclusionOur findings indicated that lower methylation rates may be a biomarker for DLB.

DOI： 10.1111/pcn.12462

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

A hypothesis for schizophrenia (SCZ) called the "microglia hypothesis" has been suggested. In SCZ, expression of triggering receptor expressed on myeloid cell 2 (TREM2) mRNA is higher in leukocytes than in healthy individuals. Here, the methylation rates of four CpG sites in TREM2 intron 1 that may bind important transcription factors and the correlation between the methylation rate and mRNA expression were determined. We compared the methylation rates in SCZ patients and age-matched controls (n = 50 each). SCZ patients had significantly lower methylation rates of CpG 2 (17.0 ± 6.7 vs. 20.2 ± 5.0; p = 0.02) and CpG 3 (23.8 ± 8.2 vs. 28.1 ± 6.2; p = 0.01). The average methylation rate (15.3 ± 5.2 vs. 17.6 ± 3.9; p = 0.009) was also lower. A significant negative correlation was found between TREM2 mRNA expression and the methylation rate of CpG 2 (r = -0.252, p = 0.012). SCZ susceptibility markers may include low methylation at TREM2 intron 1 and increased TREM2 mRNA levels. Our pilot study requires validation with higher numbers of participants and with other myeloid cell types.

DOI： 10.3389/fnins.2017.00275

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：IOS PRESS  

Background/Objective: The aim of this study was to examine the blood gene expression and methylation of ATP-binding cassette sub-family A member 7 gene (ABCA7) as a biological marker of AD.
Methods: AD subjects (n = 50; 11 males, 77.7 +/- 6.05 years old) and age-and sex-matched healthy controls (n = 50) were recruited. A single nucleotide polymorphism in ABCA7 (rs3764650), methylation rates of CpG sites in the ABCA7 promoter region, and ABCA7 mRNA expression levels in peripheral blood were examined.
Results: The distribution of the rs3764650 polymorphism in AD subjects was not different from that of controls. Although the methylation rates of AD subjects were not significantly different from those of controls, the ABCA7 mRNA expression level in AD subjects was significantly higher than that in controls. Additionally, the ABCA7 mRNA expression level in AD subjects was significantly correlated with Mini-Mental State Examination recall, the Alzheimer's Disease Assessment Scale total score, and the Clinical Dementia Rating score. We also found a significant correlation between the ABCA7 mRNA expression level and duration of illness.
Conclusion: The ABCA7 mRNA expression level in peripheral blood may be a marker for early stages of AD and disease progression regardless of rs3764650 and the methylation rate of its promoter.

DOI： 10.3233/JAD-161195

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その他リンク： http://orcid.org/0000-0003-4409-3096

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：{IOS} Press  

DOI： 10.3233/JAD-161211

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：IOS PRESS  

BACKGROUND: TOMM40 is located on chromosome 19, is in linkage disequilibrium with apolipoprotein E (APOE), andis reported in several genome-wide association studies to be associated with Alzheimer's disease (AD). OBJECTIVE: Assess APOE and TOM40 and mitochondrial genes as blood biomarkers for AD. METHODS: We examined TOMM40, PTEN-induced putative kinase 1 (PINK1), Parkin RBR E3 ubiquitin protein ligase (PARK2), and APOE mRNA expression in relation to the methylation rates of CpG sites in the upstream region of TOMM40exon 1 in peripheral leukocytes and TOMM40523 polyT genotypes in 60 AD and age- and sex-matched control subjects. RESULTS: TOMM40 mRNA expression was significantly lower in AD subjects (0.87±0.18 versus 1.0±0.23, p = 0.005), and PINK1 mRNA expression was higher in AD subjects (1.5±0.61 versus 1.0±0.52, p < 0.001). TOMM40 mRNA expression was significantly correlated with the Mini-Mental State Examination total score (r = 0.290, p = 0.027). There was no expressional change in peripheral APOE mRNA in either AD or control subjects (p = 0.32). Methylation rates in the upstream region of TOMM40exon 1 were not different between AD and control subjects (average rate: 1.37±0.99 versus 1.39±1.20, p = 0.885), and TOMM40523 polyT genotypes were also not different between AD and control subjects (p = 0.67). CONCLUSION: TOMM40 mRNA expression was lower in AD subjects and was correlated with cognitive decline. Significant changes in both TOMM40 and PINK1 mRNA may be related to mitochondrial dysfunction.

DOI： 10.3233/JAD-170361

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：TAYLOR & FRANCIS LTD  

Objectives: According to the dopamine hypothesis, several studies on the gene for the dopamine receptor D2 (DRD2) have been conducted. However, no trait biomarkers on DRD2 are available. We examined whether the methylation rates in the upstream region of DRD2 in leukocytes are different in schizophrenia (SCZ) subjects compared to control subjects.Methods: We selected seven CpG sites in the upstream region of DRD2 that may theoretically bind major transcription factors. The methylation rates in these regions of 50 medicated and 18 drug-naive SCZ subjects were compared with those of age-matched control subjects.Results: The methylation rates were significantly lower in medicated (CpG2, P&lt;0.0001; CpG4, P=0.013; CpG7, P&lt;0.0001; and average: 12.91.8 vs. 14.1 +/- 2.2, P=0.005) and drug-naive SCZ subjects (CpG1, P=0.006; CpG2, P =0.001; CpG3, P=0.001; CpG5, P =0.02; CpG6, P=0.015; CpG7, P=0.027; and average: 9.86 +/- 0.9 vs. 11.2 +/- 1.3, P=0.002).Conclusions: We confirmed low methylation rates in the upstream region of DRD2 in both medicated and drug-naive SCZ subjects. Low methylation rates of DRD2 in leukocytes may be a trait biomarker for SCZ.

DOI： 10.1080/15622975.2016.1197424

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER WIEN  

The pathological mechanisms of schizophrenia (SCZ) have not been clarified, but the microglia hypothesis has recently been discussed. We previously reported that the mRNA for a protein related to activation of microglia, triggering receptor expressed on myeloid cell 2 (TREM2), is expressed higher in peripheral leukocytes in SCZ than controls. In this study, we analyzed TREM2 mRNA expression in leukocytes from both SCZ and major depressive disorder (MDD) patients. We compared 50 SCZ patients and 42 MDD patients with age-matched controls. Levels of TREM2 mRNA in leukocytes were analyzed with quantitative real-time PCR method using TaqMan probe. TREM2 mRNA expression was significantly higher in leukocytes of SCZ subjects than controls, but the expression level was non-significantly different in MDD subjects. We observed a decrease in TREM2 mRNA expression in leukocytes from one SCZ patient after clozapine treatment. The expression did not change following ECT, but the expression level in this patient was still significantly higher than that in controls. We conclude that the high amount of TREM2 mRNA expression in leukocytes is specific to SCZ but not MDD and that changes in TREM2 mRNA expression may be a trait biomarker for SCZ.

DOI： 10.1007/s00702-016-1560-3

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

The serotonin transporter (5HTT) may be associated with the pathogenesis of major depressive disorder (MDD). The 5HTT-linked polymorphic region (5HTTLPR) genotype may determine how levels of 5HTT mRNA are influenced by promoter methylation. We examined the association of 5HTT gene methylation, which influences gene expression, and the 5HTTLPR genotype before antidepressant treatment and expression before and after treatment. The aims of this study were (1) to investigate the association between 5HTT methylation or expression in leukocytes and depression and (2) to investigate a possible effect of 5HTT methylation, expression, and genotype on clinical symptoms in MDD. The 5HTTLPR genotype was significantly associated with mean methylation levels in patients only (patients: r=0.40, p=0.035, controls: p=0.96). The mean methylation level was significantly increased in patients compared with controls (patients: 5.30 +/- 0.24, controls: 4.70 +/- 0.19, unpaired t-test, p=0.04). 5HTT expression using real-time PCR and Taqman probes was increased in unmedicated patients compared with controls and then decreased 8 weeks after antidepressant treatment. The mean 5HTT expression level was not associated with the 5HTTLPR genotype in patients or controls. Increased depressive symptoms were related to decreased levels of methylation. Copyright (C) 2016 John Wiley & Sons, Ltd.

DOI： 10.1002/hup.2527

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：CAMBRIDGE UNIV PRESS  

Background: The mean age of inpatients with schizophrenia has gradually increased in Japan and the risk of fracture in older schizophrenia patients is elevated. One possible cause may be idiopathic normal pressure hydrocephalus (iNPH). The present study aimed to evaluate the prevalence and symptoms of iNPH in older inpatients with schizophrenia.
Methods: We prospectively examined older inpatients with schizophrenia (N = 21, mean age = 70.5 +/- 5.9) in a psychiatric ward. We evaluated iNPH symptoms using the idiopathic Normal-Pressure Hydrocephalus Grading Scale (iNPHGS), Timed Up-and-Go test (TUG), Gait Status Scale (GSS), Mini-Mental State Examination (MMSE), and Neuropsychiatric Inventory (NPI). We also evaluated symptoms of schizophrenia using the Brief Psychiatric Rating Scale (BPRS) and Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS). We conducted cerebrospinal fluid (CSF) tap tests for patients with possible-iNPH.
Results: In total, three (14.3%) patients were diagnosed with possible iNPH: age, GS-Gait, GS-Cognition, TUG, 10-meter walking test, GSS, and DIEPSS were significantly increased in these compared to patients without iNPH; however, GS-Urine, MMSE, NPI, and BPRS did not differ significantly. Probable iNPH was diagnosed for two (9.5%) patients because of positive CSF tap tests.
Conclusion: The prevalence of possible and probable iNPH in older patients with schizophrenia was much higher than that reported for older people without mental illness. Of the symptoms evaluated with the tests employed, only gait disturbances, particularly walking speed, distinguished schizophrenia patients with iNPH. These findings suggest that we should pay more attention to the possibility of iNPH in older patients with schizophrenia.

DOI： 10.1017/S1041610215001763

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

ObjectiveRefeeding in patients with anorexia nervosa (AN) is associated with a risk of refeeding syndrome, which is a disruption in metabolism with a variety of features including hypophosphatemia. We evaluated the risk factors for refeeding hypophosphatemia (RH) during nutritional replenishment in Japanese patients with AN.
MethodsWe retrospectively examined clinical data for 99 female inpatients (mean age 30.910.7 years; range, 9-56 years).
ResultsRH (phosphate&lt;2.3 mg/dL) occurred within 4.8 +/- 3.7 days of hospital admission and was still observed at 28 days after admission in 21 of the 99 cases (21.2%). Oral or intravenous phosphate was given to some patients to treat or prevent RH. Patients with RH had a significantly lower body mass index, were older, and had higher blood urea nitrogen than those without RH. Severe complications associated with RH were recorded in only one patient who showed convulsions and disturbed consciousness at Day 3 when her serum phosphate level was 1.6 mg/dL.
ConclusionsThe significant risk factors for RH that we identified were lower body mass index, older age, and higher blood urea nitrogen at admission. No significant difference in total energy intake was seen between the RH and no RH groups, suggesting that RH may not be entirely correlated with energy intake. Precisely predicting and preventing RH is difficult, even in patients with AN who are given phosphate for prophylaxis. Thus, serum phosphate levels should be monitored for more than 5 days after admission. (c) 2015 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:402-406).

DOI： 10.1002/eat.22472

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：IOS PRESS  

Despite the continuing debate about the amyloid hypothesis in Alzheimer's disease (AD), the precise pathogenesis is still unclear. Mixed pathology is common and multiple different protein aggregates are seen in human postmortem brains. Aggregates consisting of the alpha-synuclein protein encoded by the Synuclein Alpha gene (SCNA) are common in both dementia with Lewy bodies and AD. We examined SNCA mRNA expression and methylation rates of the CpG island at intron 1 of SNCA in peripheral leukocytes in 50 AD and age- and sex-matched control subjects to verify whether alpha-synuclein pathology affects the AD pathogenesis. SNCA mRNA expression in AD subjects was significantly higher than that in control subjects (1.62 +/- 0.73 versus 0.98 +/- 0.50, p&lt; 0.001). We found significant differences between AD and control subjects at seven CpG sites (average rate; 8.8 +/- 2.7 versus 9.5 +/- 2.5, respectively: p = 0.027). The methylation rates tended to be lower in AD subjects at all CpG sites. We conclude that mRNA expression and methylation of SNCA intron 1 are altered in AD, which may be caused by Lewy body pathology in AD.

DOI： 10.3233/JAD-160430

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：KARGER  

Background/Aim: The aim of this study was to elucidate the relationship between Alzheimer's disease (AD) and the serotonin transporter gene (SLC6A4). Methods: AD subjects (n = 43) and controls (n = 47) were recruited and evaluated. In leukocytes, we evaluated two polymorphisms in SLC6A4, the serotonin transporter length polymorphic region (5-HTT-LPR) and rs25531, as well as methylation rates of the SLC6A4 promoter region and the SLC6A4 mRNA expression level. We also performed a meta-analysis to examine the relationship between the frequency of the L allele and the risk of AD. Results: The distributions of 5-HTT-LPR and rs25531 polymorphisms in AD subjects were not different from those of controls. Although the methylation rates in AD subjects were not significantly different from those of controls, the expression level in AD subjects was significantly higher than in controls. Additionally, the expression level in AD subjects was significantly correlated with apathy. Meta-analysis revealed that the L/L genotype significantly reduced the risk of AD, but only in the Caucasian population. Conclusion: Higher SLC6A4 mRNA expression in leukocytes in AD was associated with apathy regardless of SLC6A4 genotypes and methylation rates of the promoter region. The L/L genotype may reduce the risk of AD in the Caucasian population. (C) 2016 S. Karger AG, Basel

DOI： 10.1159/000447324

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：{IOS} Press  

DOI： 10.3233/JAD-160430

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Cambridge University Press  

Objective Severe depression may be a risk factor for diagnostic conversion into bipolar disorder (BD), and psychotic depression (PD) has been consistently associated with BD. The aims of the present study were to investigate the stability of the diagnosis of severe depression and the differences between PD and non-psychotic severe depression (non-PD), as well as to assess the effectiveness of electroconvulsive therapy (ECT). Methods Patients who were hospitalised for severe depression (diagnosed according to ICD-10) both with and without psychotic symptoms (n=89
mean age=55.6 years, SD=13.9) from 2001 to 2010 were retrospectively assessed. Results By the 75th month of follow-up assessments, 11(12.4%) patients had developed BD. Among these 11 converters, nine had developed BD within 1 year after admission. Only sub-threshold hypomanic symptoms were significantly related to developing BD. The number of depressive episodes and history of physical diseases were significantly increased in non-PD compared with PD patients, whereas ECT was significantly increased in PD compared with non-PD patients. There was a significant association between length of stay at the hospital and the number of days between admission and ECT. Conclusion Sub-threshold hypomanic symptoms may represent a prodrome of BD or an indicator of an already manifest phenotype, especially in older patients, which suggests cautious use of antidepressants. In severe depression, non-PD may often occur secondary to physical diseases and patients may experience increased recurrences compared with PD patients, which may be a more 'primary' disorder and often requires ECT treatments. ECT is effective for severe depression regardless of the presence of any psychotic feature
the earlier ECT is introduced, the better the expected treatment outcome.

DOI： 10.1017/neu.2014.42

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

Objective: Recent research has suggested that a functional polymorphism in the promoter region of the serotonin transporter gene (serotonin transporter-linked polymorphic region, 5HTTLPR) may be implicated in gene-environment interactions leading to major depressive disorder (MDD).
Methods: Our study examined the association between 5HTTLPR and clinical variables of MDD in the Japanese population. We genotyped 5HTTLPR in 216 patients with MDD and 213 age- and sex-matched controls.
Results: The genotype distributions and allele frequencies were similar in the patients and controls. When the relationships between the polymorphism and several clinical variables (i.e., age of onset, number of episodes, presence of psychotic features, suicidal behavior, and family history) were examined, the dose of the long (1) allele had significant effects on the age of onset.
Conclusion: These results suggest that 5HTTLPR may not be entirely related to the development of MDD but may be related to the age of onset of MDD, which may be due to gene-environment interactions in the Japanese population.
Limitations: Because of the low frequencies of psychotic features and suicidal behavior, our results must be treated with caution until they are replicated in larger numbers of Japanese samples. MDD patients did not undergo a structured interview. Clinical information from the medical records may have not been complete. (C) 2015 Elsevier B.V. All rights reserved,

DOI： 10.1016/j.jad.2015.05.009

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PUBLIC LIBRARY SCIENCE  

TREM2 and TYROBP are causal genes for Nasu-Hakola disease (NHD), a rare autosomal recessive disease characterized by bone lesions and early-onset progressive dementia. TREM2 forms a receptor signaling complex with TYROBP, which triggers the activation of immune responses in macrophages and dendritic cells, and the functional polymorphism of TREM2 is reported to be associated with neurodegenerative disorders such as Alzheimer's disease (AD). The objective of this study was to reveal the involvement of TYROBP and TREM2 in the pathophysiology of AD and schizophrenia. Methods: We investigated the mRNA expression level of the 2 genes in leukocytes of 26 patients with AD and 24 with schizophrenia in comparison with age-matched controls. Moreover, we performed gene association analysis between these 2 genes and schizophrenia. Results: No differences were found in TYROBP mRNA expression in patients with AD and schizophrenia; however, TREM2 mRNA expression was increased in patients with AD and schizophrenia compared with controls (P &lt; 0.001). There were no genetic associations of either gene with schizophrenia in Japanese patients. Conclusion: TREM2 expression in leukocytes is elevated not only in AD but also in schizophrenia. Inflammatory processes involving TREM2 may occur in schizophrenia, as observed in neurocognitive disorders such as AD. TREM2 expression in leukocytes may be a novel biomarker for neurological and psychiatric disorders.

DOI： 10.1371/journal.pone.0136835

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

Background: Development of easy-to-use biological diagnostic tests for major depressive disorder (MDD) may facilitate MDD diagnosis and delivery of optimal treatment. Here, we examined leukocyte gene expression to develop a biological diagnostic test for MDD.
Methods: 25 drug-naive MDD patients (MDDs) and 25 age- and sex-matched healthy subjects (Controls) participated in a pilot study. A subsequent replication study involved 20 MDDs and 18 Controls. We used custom-made PCR array plates to examine mRNA levels of 40 candidate genes in leukocyte samples to assess whether any combination of these genes could be used to differentiate MDDs from Controls based on expression profiles.
Results: Among 40 candidate genes, we identified a set of seven genes (PDGFC, SLC6A4, PDLIM5, ARKGA P24, PRNP, HDAC5, and IL1R2), each of which had expression levels that differed significantly between MDD and Control samples in the pilot study. To identify genes whose expression best differentiated between MDDs and Controls, a linear discriminant function was developed to discriminate between MDDs and Controls based on the standardized values of gene expression after Z-score transformation. Ultimately, five genes (PDGFC, SLC6A4, ARHGAP24, PRNP, and HDAC5) were selected for a multi-assay diagnostic test. In the pilot study, this diagnostic test demonstrated sensitivity and specificity of 80% and 92%, respectively. The replication study yielded nearly identical results, sensitivity of 85% and specificity. of 89%.
Conclusions: Using leukocyte gene expression profiles, we could differentiate MDDs from Controls with adequate sensitivity and specificity. Additional markers not yet identified might further improve the performance of this test. (C) 2015 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jpsychires.2015.03.004

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：CAMBRIDGE UNIV PRESS  

Objective: Severe depression may be a risk factor for diagnostic conversion into bipolar disorder (BD), and psychotic depression (PD) has been consistently associated with BD. The aims of the present study were to investigate the stability of the diagnosis of severe depression and the differences between PD and non-psychotic severe depression (non-PD), as well as to assess the effectiveness of electroconvulsive therapy (ECT).
Methods: Patients who were hospitalised for severe depression (diagnosed according to ICD-10) both with and without psychotic symptoms (n = 89; mean age = 55.6 years, SD = 13.9) from 2001 to 2010 were retrospectively assessed.
Results: By the 75th month of follow-up assessments, 11(12.4%) patients had developed BD. Among these 11 converters, nine had developed BD within 1 year after admission. Only sub-threshold hypomanic symptoms were significantly related to developing BD. The number of depressive episodes and history of physical diseases were significantly increased in non-PD compared with PD patients, whereas ECT was significantly increased in PD compared with non-PD patients. There was a significant association between length of stay at the hospital and the number of days between admission and ECT.
Conclusion: Sub-threshold hypomanic symptoms may represent a prodrome of BD or an indicator of an already manifest phenotype, especially in older patients, which suggests cautious use of antidepressants. In severe depression, non-PD may often occur secondary to physical diseases and patients may experience increased recurrences compared with PD patients, which may be a more 'primary' disorder and often requires ECT treatments. ECT is effective for severe depression regardless of the presence of any psychotic feature; the earlier ECT is introduced, the better the expected treatment outcome.

DOI： 10.1017/neu.2014.42

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCI LTD  

The physical benefits of subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease (PD) patients are well documented, but the mental benefits are uncertain, particularly in Japanese patients. This study evaluated the clinical and neuropsychological characteristics before and after STN-DBS surgery in Japanese PD patients. PD patients (n = 13, age 67.0 +/- 7.8 years) were evaluated pre-surgery (baseline) and at 1 and 6 months post-surgery by two trained psychiatrists. The motor symptoms were assessed by the Unified Parkinson's Disease Rating Scale (UPDRS) motor score. The neuropsychological and psychiatric tests performed were the Mini-Mental State Examination, the Wisconsin Card Sorting Test (WCST), the Verbal Fluency Test (VET), the Hamilton Depression Rating Scale and the Hamilton Anxiety Rating Scale (HAM-A). The UPDRS motor score (p &lt; 0.001) and HAM-A score (p = 0.004) showed significant improvement at 1 month post-surgery, but a significant decline was observed in the WCST total error (p = 0.005) and the semantic VFT score (p &lt; 0.001). The phonetic VFT also showed a substantial decline (p = 0.015) at 1 month post-surgery. At 6 months post-surgery, the improvement in the UPDRS motor score was maintained, and the scores on the neuropsychological and psychiatric tests had returned to baseline. Although bilateral STN-DBS did not appear to have long-term effects on neuropsychological and psychiatric outcomes, the microlesion effects associated with STN-DBS appear to increase the risk of transient cognitive and psychiatric complications. These complications should be monitored by careful observation of neurological and psychiatric symptoms. (C) 2014 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jocn.2013.12.020

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記述言語：英語   出版者・発行元：ELSEVIER SCIENCE INC  

We report a 59-year-old man with isolated adrenocorticotropin (ACTH) deficiency. The patient presented with sudden onset of delusions and hallucinations at the age of 54, which resolved gradually without treatment. Subsequently, the patient manifested stereotypy, wandering, hypobulia, and autistic symptoms, and was treated with antipsychotics for 1 year without any improvement. He suffered from neuroleptic malignant syndrome-like symptoms at the age of 59. A thorough endocrine assessment revealed isolated ACTH deficiency. After hydrocortisone supplementation, the physical and psychiatric symptoms improved dramatically. Clinicians should consider this rare disease when diagnosing patients with refractory psychiatric symptoms and unique physical symptoms of isolated ACTH deficiency. (C) 2014 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.genhosppsych.2014.02.012

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

ObjectivesTo elucidate the molecular effects of lithium, we studied global gene expression changes induced by lithium in leukocytes from healthy subjects.
MethodsEight healthy male subjects participated in this study. Lithium was prescribed for weeks to reach a therapeutic serum concentration. Leukocyte counts and serum lithium concentrations were determined at baseline (before medication), after 1 and 2weeks of medication and at 2weeks after stopping medication. Gene expression profiling was performed at each time point using Agilent G4112F Whole Human Genome arrays (The Agilent Technologies, Santa Clara, CA, USA). Expression of some candidate genes was also assessed by real-time polymerase chain reaction (PCR).
ResultsGene ontology analysis revealed that the cellular and immune responses to stimulus and stress indeed played a major role in the cellular response to lithium treatment. Pathway analysis revealed that the interleukin 6 pathway, the inhibitor of differentiation pathway, and the methane metabolism pathway were regulated by lithium. Using real-time PCR, we also confirmed that five candidate genes in these pathways were significantly changed, including suppressor of cytokine signaling 3 and myeloperoxidase.
ConclusionsOur investigation suggests that the molecular action of lithium is mediated in part by its effects on the cellular and immune response to stimulus and stress followed by the interleukin 6, inhibitor of differentiation, and methane metabolism pathways. Copyright (c) 2014 John Wiley & Sons, Ltd.

DOI： 10.1002/hup.2381

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：3  

Objective: Fat-mass and obesity-associated (FTO) gene is known to be involved in the pathophysiology of obesity and a single-nucleotide polymorphism (SNP) rs9939609 of FTO gene is repeatedly confirmed to be associated with body mass index (BMI) and obesity. The aim of this study is to elucidate effects of FTO gene polymorphism on BMI in Japanese patients with schizophrenia and healthy subjects. Methods: Three hundred fifty one patients with schizophrenia and 342 age- and sex- matched healthy subjects participated in the study. Information on BMI and antipsychotic medication was also collected from patients and healthy subjects. Genotype of the FTO SNP rs9939609 was determined by TaqMan SNP Genotyping Assays. Results: There was no significant difference in BMI between patients and healthy subjects. No significant difference in BMI was observed among any medications. We observed no significant difference in rs9939609 allele frequencies between patients and healthy subjects. There was a significant difference in BMI between healthy subjects with risk (AA or TA) genotypes and those with TT genotype. We also observed a significant positive correlation between the number of risk allele (A allele) and BMI in healthy subjects. Conclusion: Our study suggested that FTO rs9939609 polymorphism might have some impacts on the BMI in healthy subjects, but might not have same impacts on the BMI of patients with schizophrenia. Copyright © 2012, Korean College of Neuropsychopharmacology.

DOI： 10.9758/cpn.2012.10.3.185

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

Objectives Vascular endothelial growth factor (VEGF) is thought to be involved in the pathophysiology of mood disorders and the target of antidepressants. The aim of this study was to elucidate molecular effects of lithium on VEGF expression by using leukocytes of healthy subjects and patients with bipolar disorder.
Methods Eight healthy male subjects participated in the first study. Lithium was prescribed for 2 weeks, enough to reach therapeutic serum concentration. Leukocyte counts and serum lithium concentrations were determined at baseline, at 1- and 2-week medication, and at 2 weeks after stopping medication. VEGF mRNA levels were also examined in nine lithium-treated bipolar patients and healthy controls in the second study.
Results In the first study, leukocyte counts were significantly increased at 2 weeks compared with those at baseline and were normalized after 2 weeks. VEGF mRNA levels were significantly decreased at 2 weeks and after 2 weeks compared with those at baseline. Consistent with the first study, VEGF mRNA levels were significantly decreased in the lithium-treated bipolar patients compared with healthy controls.
Conclusions Our investigation suggests that VEGF mRNA expression may be useful as a peripheral marker of the effects of lithium. Copyright (C) 2011 John Wiley & Sons, Ltd.

DOI： 10.1002/hup.1215

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記述言語：英語   出版者・発行元：INFORMA HEALTHCARE  

Depression is a disorder not only in the central nervous system (CNS), but also in the systemic neuroendocrine, autonomic nervous, and immune systems. The changes in these systems have been widely studied in depression by using serum proteins because they are easily and repetitively studied before, during, and after treatment. Recently, gene expressions in the peripheral blood leukocytes have been used to assess the depressive changes in the CNS by DNA microarrays and/or real-time polymerase chain reaction (PCR) methods. These studies will give us clues to assess depression because circulating peripheral leukocytes are influenced by systems that underlie depression, and the quantification of mRNAs in them is methodologically precise and easier than that of protein. In this paper, we review the studies on the leukocyte gene expression, including our own, and discuss the limitations and strengths of the current gene expression-based molecular assessment of depression by the leukocyte mRNA expression.

DOI： 10.1080/07853890802082088

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掲載種別：研究論文（学術雑誌）  

Recent researches have suggested that brain-derived neurotrophic factor (BDNF) may be implicated in the pathophysiology of mood disorder. This study examined the association between the BDNF Val66Met polymorphism and major depressive disorder (MDD) in a Japanese population. We genotyped the BDNF Val66Met polymorphism in 154 major depressive patients and 154 age- and sex-matched control subjects. The genotypic distributions and allele frequencies were similar among the patients and control subjects. When the relationships of the polymorphism with several clinical variables (i.e., age, sex, age of onset, number of episode, presence of psychotic features, suicidal behavior, and family history) were examined, the dose of Met allele had significant effects on psychotic feature and suicidal behavior and family history. These results suggest that the BDNF Val66Met polymorphism is not related to the development of MDD but related to clinical features of MDD in a Japanese population. © 2007 Wiley-Liss, Inc.

DOI： 10.1002/ajmg.b.30520

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掲載種別：研究論文（学術雑誌）  

Vascular endothelial growth factor (VEGF) has been implicated in neuronal survival, neuroprotection, regeneration, growth, differentiation, and axonal outgrowth, which are known to be involved in the pathophysiology of major depressive disorder (MDD). Recently, the VEGF mRNA expression in the peripheral leukocytes from Alzheimer's disease or cardiovascular disease was reported to be changed. We hypothesized that the expression of the VEGF mRNA in the peripheral leukocytes may be a good candidate for the biological marker for MDD. Thirty two patients with MDD and age- and sex-matched control subjects were included in this expression study. The VEGF mRNA levels in the peripheral leukocytes from drug-naive MDD patients were significantly higher than those from the control subjects and the magnitude of the decrease of VEGF mRNA after 8-week treatment significantly correlated with clinical improvement. Then, we genotyped two single nucleotide polymorphic markers of VEGF gene, which were reported to be associated with amyotrophic lateral sclerosis and Alzheimer's disease, in patients with MDD and control subjects (n = 154, each). We did not find any significant association between these markers and MDD or its clinical subtypes. Our investigation indicates that the higher expression levels of VEGF mRNA in the peripheral leukocytes are associated with the depressive state and their recovery after treatment may be associated with the clinical improvement. © 2006 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.pnpbp.2006.12.011

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記述言語：英語   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

Background: Gene expressions of the peripheral leukocytes in depressive patients might reflect the systemic dysfunction of major depression. We determined mRNA expression levels of Historic deacetylase 5 (HDAC5) gene and cyclic AMP response element-binding protein 1 (CREB) gene in the leukocyte of depressive patients. HDAC5 and CREB are reported to be important targets of antidepressants, the latter being located in the downstream of the former in lymphocyte calcium signaling.
Methods: 25 patients with major depression and 25 age- and sex-matched healthy controls were included in this study. Twenty patients were able to be followed up until the 8 week-treatment. The mRNA levels were determined by a quantitative RT-PCR method.
Result: Levels of HDAC5 and CREB mW4A were significantly higher in drug-free depressive patients than those of controls and the higher mRNA levels decreased to control levels after 8-week paroxetine treatment. There were positive correlation between levels of HDAC5 and CREB. Conclusion: Our results suggest the alteration of HDAC5 and CREB gene expression in the systemic pathophysiology of major depression.
(c) 2007 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.pnpbp.2006.12.014

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掲載種別：研究論文（学術雑誌）  

LIM (PDLIM5) is a small protein that interacts with protein kinase C-epsilon and the N-type calcium channel alpha-1B subunit and modulates neuronal calcium signaling. Recently, the LIM mRNA expression in postmortem brains and immortalized lymphoblastoid cells from mood disorder patients was reported to be changed and seems to be involved in its pathophysiology. We hypothesized that the expression of the LIM mRNA in the native peripheral leukocytes may be a good candidate for the biological marker for mood disorders. Twenty patients with major depression and age- and sex-matched control subjects were included in this expression study. The LIM mRNA levels in the peripheral leukocytes from drug-naive depressive patients were significantly lower than those from control subjects and increased significantly after 4-week paroxetine treatments, to almost the same level as controls'. Hamilton depressive scores (HAM-D) were improved about 50% after 4-week treatment but neither paroxetine concentrations nor the changes of HAM-D scores showed significant correlation with the change of the mRNA levels. Then, we genotyped three single nucleotide polymorphic markers of LIM gene, which were reported to be associated with bipolar disorder in patients with major depression and control subjects (n = 130, each), but there were no associations between these SNPs and major depression. Our investigation indicates that the lower expression levels of LIM mRNA in the peripheral leukocytes are associated with the depressive state and that its recovery after treatment may be an adaptive change induced by the antidepressant. © 2006 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.neulet.2006.02.044

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER IRELAND LTD  

Serotonin transporter (5HTT) is thought to be involved in the pathophysiology of major depression and the target of antidepressants. We hypothesized that 5HTT mRNA levels in peripheral leukocytes may be associated with depressive states and the therapeutic response to antidepressant treatments. Fifteen patients with major depression and age-, sex-matched control subjects were studied. 5HTT mRNA levels were determined with quantitative real-time PCR method. 5HTT mRNA levels in leukocytes were significantly higher in depressive patients at baseline (before medication) than in control subjects. 5HTT mRNA levels were decreased significantly after 8 weeks of paroxetine medication compared with those at baseline. Our investigation suggested that the increased expression of 5HTT mRNA in peripheral leukocytes may be related with the pathophysiology of depression and its reduction after treatment may reflect the adaptive change induced by the antidepressant. (C) 2005 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.neulet.2005.06.048

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIM: Recent studies have implicated autophagy in both weight regulation and depression. This study aimed to investigate the relationship between stress-induced weight loss and autophagy-related gene expression in a mouse model of depression. METHOD: Male C57BL/6 mice were subjected to a chronic immobilization stress (CIS) protocol for 14 days to induce depressive-like behavior. Body weight was measured before and after the CIS, and depressive-like behavior was assessed using the tail suspension test (TST). The expression levels of autophagy-related genes (Atg5, Atg7, Atg12, Becn1, Mmp9, Fkbp5, and Map1lc3b) in the hippocampus and midbrain were evaluated using reverse transcription-quantitative PCR (RT-qPCR). Serum cortisol levels were also measured. RESULTS: The CIS resulted in significant weight loss and increased immobility time in the TST, indicating depressive-like behavior. Serum cortisol levels were not different between CIS-depression model and control mice. In the hippocampus, the expression levels of Fkbp5, Mmp9, and Map1lc3b were significantly higher in CIS-depression model mice than in control mice. In the midbrain, the expression levels of Fkbp5 and Mmp9 were significantly higher in CIS-depression model mice than in control mice. Increased autophagy-related gene expressions in CIS-depression model mice were consistent with the previous studies in the postmortem brains of patients with depression. A significant negative correlation was also found between Fkbp5 mRNA expression in the hippocampus and the weight change ratio before and after the CIS. CONCLUSION: The findings suggest that enhanced autophagy may be related to the pathology of depression and that Fkbp5, an autophagy regulator, mediates stress-induced weight loss.

DOI： 10.1002/npr2.12515

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DOI： 10.1002/npr2.70005

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DOI： 10.1002/npr2.12499

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Oxford University Press (OUP)  

Abstract

Background

Antipsychotics are used in treatment of schizophrenia. Although antipsychotic monotherapy is recommended in most guidelines, the prescription rate of antipsychotic polypharmacy is still high, and the rates of antipsychotics and other concomitant psychotropics are different among each institution.

Although the detailed causes for these differences are not well known, one of the reasons of psychotropics polypharmacy, including antipsychotics polypharmacy, may be associated with severity of schizophrenia including treatment resistant schizophrenia (TRS). With regard to TRS, institutions with a low TRS examination rate was associated with a low clozapine prescription rate. Thus, the differences of institutions, which is available to clozapine prescriptions or not, may be affected the treatment characteristics of overall schizophrenia in each institution.

Aims &amp; Objectives

We examined the characteristics of psychotropic prescriptions, including antipsychotics, at the time of discharge depending on whether the institutions were available to clozapine prescriptions or not.

Methods

We assessed 8155 schizophrenia patients nationwide from 207 institutions from 2017 to 2020 in Japan. We divided patients into clozapine-available institutions (CAI) group and clozapine-unavailable institutions (CUI) group. We analyzed and compared the psychotropic prescription data at discharge between two groups. We defined “antipsychotic monotherapy” as the prescription of a single antipsychotic regardless of concomitant use of other psychotropics, and we defined “complete antipsychotic monotherapy” as the prescription of a single antipsychotic without concomitant use of other psychotropics. Furthermore, to investigate that the diagnosis of subgroups about TRS or not may influence the treatment, we analyzed the description of subgroups about TRS (DSTRS) or no description of subgroups about TRS (NDSTRS), and we divided the patients into four groups such as CAI with DSTRS, CAI with NDSTRS, CUI with DSTRS, and CUI with NDSTRS, and compared between four groups using the same method. We defined p &amp;lt;1.9 × 10-3 (0.05/27) as significant by post hoc analyses for multiple comparisons of categories.

Results

The number of patients was 6793 in the CAI group and 1362 in the CUI group. The rate of antipsychotic monotherapy in the CAI group was significantly higher than that in the CUI group (58.3% vs 50.7%), and the rate of complete antipsychotic monotherapy in the CAI group was significantly higher than that in the CUI group (20.4% vs 15.6%). The rate of DSTRS was significantly lower in the CAI group than the CUI group (43.6% vs 49.4%). The rate of antipsychotic monotherapy (56.0%) and complete antipsychotic monotherapy (20.0%) in the CAI group except patients prescribed clozapine were also significantly higher than that in the CUI group. The rate of antipsychotic monotherapy in the CAI with DSTRS group (63.3%) and the rate of complete antipsychotic monotherapy in the CAI with DSTRS group (22.6%) were significantly higher than that in the other three groups.

Discussion &amp; Conclusion

Both establishment of clozapine prescription and the precise diagnosis of subgroups about TRS or not at discharge in each institution would lead clinicians to the treatment which may contribute to the higher psychotropic monotherapy rate for overall schizophrenia treatment.

DOI： 10.1093/ijnp/pyae059.282

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The genetic architecture of white matter lesions (WMLs) in Asian populations has not been well-characterized. Here, we performed a genome-wide association study (GWAS) to identify loci associated with the WML volume. Brain MRI and DNA samples were collected from 9479 participants in the Japan Prospective Studies Collaboration for Aging and Dementia (JPSC-AD). The GWAS confirmed three known WML-associated loci (SH3PXD2A, GFAP, and TRIM47). The lead variant of GFAP was a common missense variant (p.D295N) in East Asians. Meta-GWAS using the publicly available summary statistics of UK Biobank identified one previously unreported locus 6q23.2 (SLC2A12). Integration with expression quantitative trait locus data implied the newly identified locus affects SLC2A12 expression. The effect sizes of 20 lead variants at the WML-associated loci were moderately correlated between JPSC-AD and UK Biobank. These results indicate that the alteration in GFAP protein caused by the common missense variant in East Asians influences the WML volume.

DOI： 10.1038/s41525-024-00431-x

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DOI： 10.1002/mgg3.70008

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The frequency of behavioral and psychological symptoms of dementia (BPSD) is high, and it is a challenge to elucidate its neural substrates underlying their development. In recent years, many findings have been reported on the relationship between BPSD and brain volume in dementia patients. However, the results are not fully conclusive. Furthermore, there have been few population-based studies. Therefore, the relationship between BPSD and brain volume was investigated as an exploratory study. Of the 927 older persons who participated in the fifth Nakayama study, 90 were included in this analysis, consisting of 52 patients with mild cognitive impairment and 38 patients with dementia, with head MRI and the Neuropsychiatric Inventory (NPI) data. Multiple regression analysis was used to examine the association between the total score of each BPSD score on the NPI and brain volume estimated by FreeSurfer. On multivariate adjustment, even after false discovery rate correction, insular cortical volumes decreased significantly as total scores for apathy/indifference increased (p value = 0.002, q-value = 0.01). Similarly, total brain volume decreased significantly as total scores for appetite and eating disturbance increased (p value = 0.03), and parietal, temporal, and hippocampal cortical volumes also decreased significantly as total scores for appetite and eating disturbance increased (all p and q values < 0.05). This study's results suggest that apathy is negatively correlated with insular cortical volume, and that appetite and eating disturbance are also correlated with brain regions, including parietal, temporal, and hippocampal volume in a community-dwelling older population.

DOI： 10.1038/s41598-024-77477-5

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記述言語：日本語   出版者・発行元：(一社)日本認知症学会  

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掲載種別：研究論文（学術雑誌）  

DOI： 10.3390/clinpract14050167

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: We report the final results of treatment with aripiprazole, blonanserin, and paliperidone from the Japan Useful Medication Program for Schizophrenia (JUMPs), a 104-week naturalistic study. METHODS: JUMPs was an open-label, three-arm, randomized, parallel-group, 104-week study. Patients aged ≥ 20 years with schizophrenia requiring antipsychotic treatment or a switch from previous therapy were enrolled. The primary endpoint was treatment discontinuation rate over 104 weeks. Secondary endpoints included remission rate, Personal and Social Performance (PSP), safety, Positive and Negative Syndrome Scale (PANSS), and quality of life (QOL; EuroQol-5 dimension). RESULTS: In total, 251 patients received aripiprazole (n = 82), blonanserin (n = 85), or paliperidone (n = 84). Treatment discontinuation rates (aripiprazole, 80.5%; blonanserin, 81.2%; paliperidone, 71.4%) were not significantly different (p = 0.2385) among the treatment groups at 104 weeks; comparable outcomes were observed for endpoints, including remission (42.9%, 46.7%, and 45.8%), PANSS, and safety. In the overall cohort, while the improvement in the PSP total score at Week 104 was not significantly different from baseline, a significant improvement (p < 0.05) in QOL and total PANSS scores (including all subscales) was observed at Week 104 compared with baseline. Multivariable analysis identified a shorter disease duration and a higher chlorpromazine-equivalent antipsychotic dosage level (≥ 1000 mg) before switching to monotherapy as predictors of treatment discontinuation. CONCLUSIONS: The 104-week treatment outcomes were comparable between groups; the overall trend of improvement in remission rate, safety, and QOL suggests the importance of continued treatment. CLINICAL TRIAL REGISTRATION: UMIN-Clinical Trials Registry UMIN000007942 (public release date: 14/05/2012).

DOI： 10.1186/s12888-024-06031-4

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/npr2.12417

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記述言語：日本語   出版者・発行元：(株)星和書店  

カタトニアは,昏迷のような運動活動性の低下から,外的刺激の影響によらない興奮などの運動活動性の亢進まで幅がある複雑な臨床像を特徴とする精神運動性の障害であり,かつては「緊張病」として統合失調症の亜型の一つであったが,現在では,統合失調症を含め精神疾患に関連するもの,他の医学的な疾患に関連するもの,特定不能のものにわけられる症候群であるため,カタトニアを起こす原因疾患を鑑別することが重要である。カタトニアの治療は輸液などによる全身状態の管理に加え,原因となる疾患の治療を行うことが重要であるが,カタトニアに対してはbenzodiazepine受容体作動薬か電気けいれん療法がよく用いられる。統合失調症によるカタトニアに関してはこれらに加え,非定型抗精神病薬も治療の選択肢に上がりうるが,悪性症候群の出現やカタトニアの症状を悪化させる可能性もあるため注意する必要がある。(著者抄録)

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIM: To assess the association between plasma amyloid β (Aβ) 42/40, phosphorylated tau (p-τ)181, glial fibrillary acidic protein (GFAP), or neurofilament light chain (NfL) and the risk of dementia and to determine whether these plasma biomarkers could improve the ability to predict incident dementia in a general older population. METHODS: A total of 1346 Japanese community-dwelling individuals aged ≥65 years without dementia were followed prospectively for 5.0 years. Plasma biomarkers were quantified using a Simoa HD-X analyzer. A Cox proportional hazards model was used to estimate the hazard ratios of each plasma biomarker level for the risk of dementia. RESULTS: During the follow-up, 151 participants developed dementia, of whom 108 had Alzheimer disease (AD) and 43 non-Alzheimer dementia (non-AD). Lower plasma Aβ42/40 levels and higher plasma p-τ181 levels were significantly associated with developing AD but not non-AD, whereas significant associations were observed between higher plasma levels of GFAP and NfL and risk of both AD and non-AD (all P for trend <0.05). In addition, adding these four plasma biomarkers into a model consisting of the total score of the dementia risk model significantly improved the predictive ability for incident dementia. CONCLUSION: Our findings suggest that plasma Aβ42/40 and p-τ181 are specific markers of AD, and plasma GFAP and NfL are potential biomarkers for all-cause dementia in the general Japanese older population. In addition, the measurement of these plasma biomarkers may be a useful and relatively low-invasive procedure for identifying individuals at high risk for developing dementia in clinical practice.

DOI： 10.1111/pcn.13661

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掲載種別：研究論文（学術雑誌）  

Reports on polypharmacy strategies for patients with schizophrenia and major depressive disorder (MDD) are scarce. The nationwide Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment (EGUIDE) project has been used to train psychiatrists on the guidelines for treatment of schizophrenia and MDD. This study aimed to determine whether the EGUIDE program enabled more appropriate evidence-based treatment of outpatients with schizophrenia and MDD. The types and doses of all psychotropics were analyzed in 174 and 147 patients with schizophrenia and MDD, respectively, in 2018 before the EGUIDE program and in 2019 and 2020 after the program. There were no significant differences in the rate of monopharmacy with antipsychotics for schizophrenia; however, the prescriptions of first-generation antipsychotics, anticholinergics, and benzodiazepines for schizophrenia decreased significantly after the program. There were also no significant differences in antidepressant monopharmacy rates for MDD; however, the prescriptions of benzodiazepines in patients with MDD decreased significantly after the program. Significant positive correlations were found between the number of psychotropic prescriptions and dosage of benzodiazepines. In conclusion, the EGUIDE project has improved the prescribing behavior for outpatients with schizophrenia and depression. Therefore, the guideline training program may be useful for regulating the prescribing behavior among physicians.

DOI： 10.1016/j.psycom.2024.100158

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1177/25424823241307878

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記述言語：日本語   出版者・発行元：(株)ワールドプランニング  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIM: This study aims to examine the real-world effectiveness of education regarding clinical guidelines for psychiatric disorders using 'the Effectiveness of guidelines for dissemination and education in psychiatric treatment (EGUIDE)' project. METHODS: The EGUIDE project is a nationwide prospective implementation study of two clinical practice guidelines, i.e., the Guideline for Pharmacological Therapy of Schizophrenia and the Treatment Guidelines for Major Depressive Disorders, in Japan. Between 2016 and 2019, 782 psychiatrists belonging to 176 hospitals with psychiatric wards participated in the project and attended lectures on clinical practice guidelines. The proportions of guideline-recommended treatments in 7405 patients with schizophrenia and 3794 patients with major depressive disorder at participating hospitals were compared between patients under the care of psychiatrists participating in the project and those not participating in the project. Clinical and prescribing data on the patients discharged from April to September each year from participating hospitals of the project were also analyzed. RESULTS: The proportions of three quality indicators (antipsychotic monotherapy regardless of whether other psychotropics medication, antipsychotic monotherapy without other psychotropics and no prescription of anxiolytics or hypnotics) for schizophrenia were higher among participating psychiatrists than among nonparticipating psychiatrists. As similar results were obtained in major depressive disorder, the effectiveness of the project for the dissemination of guideline-recommended treatment has been replicated. CONCLUSION: This strategy of providing education regarding the clinical guidelines for psychiatric disorders was effective in improving the treatment-related behavior of psychiatrists. The use of this education-based strategy might contribute to resolving the mental health treatment gap.

DOI： 10.1111/pcn.13578

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

BACKGROUND: Studies have shown that decreased gait speed is associated with impaired cognitive function. However, whether this association is equivalent across ages or genders in the older population remains unclear. Thus, we examined the association between mild cognitive impairment (MCI) and gait speed emphasising the influence of age and gender. METHODS: Overall, 8233 Japanese participants aged ≥65 years were enrolled in this cross-sectional study between 2016 and 2018. After stratification by gender and age group, the participants' gait speeds were divided into quintiles, and the difference in MCI prevalence at each gait speed quintile was calculated. Logistic regression analyses were performed to assess the odds of MCI for each quintile and to assess the influence of age and gender. RESULTS: Males had a consistently higher prevalence of MCI than females. The odds of MCI were increased as gait speed decreased. Logistic regression analyses revealed that in the multivariable-adjusted model 2, the odds ratios (95% confidence interval; CI) for MCI were 2.02 (1.47-2.76) for females and 1.75 (1.29-2.38) for males in the slowest gait speed quintiles compared to the fastest quintile. In the stratified analyses, only males showed an age-dependent increase in the associations between gait speed and MCI, while females exhibited comparable associations across age groups. CONCLUSIONS: Reduced gait speed was associated with increased odds of MCI, and this association may vary according to gender and age. Therefore, gait speed could serve as a valuable screening tool for MCI, with gender- and age-dependent clinical implications.

DOI： 10.1111/psyg.13013

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掲載種別：研究論文（学術雑誌）  

<h4>Background and objectives</h4>Epidemiological evidence has shown that social isolation, a low frequency of social contact with others, is associated with the risk of dementia and late-life depressive symptoms. Therefore, we hypothesized that low frequency of social contact may be involved in brain atrophy, and depressive symptoms may play some role in this relationship. We aimed to evaluate the association between low frequency of social contact and the volumes of various brain regions and to assess the extent to which depressive symptoms mediate these relationships from a large population-based multisite cohort study.<h4>Methods</h4>Dementia-free community-dwelling Japanese aged ≥65 years underwent brain MRI scans and a comprehensive health examination. Frequency of contact with non-cohabiting relatives and friends was determined by asking a single question with four categories: everyday, several times a week, several times a month, and seldom. Total and regional brain volumes, intracranial volume (ICV) and white matter lesions volume were estimated using FreeSurfer software. The associations between frequency of social contact and brain volumes per ICV were examined using analyses of covariance. Mediation analyses were conducted to calculate the proportion of the associations explained by depressive symptoms.<h4>Results</h4>We included 8,896 participants. The multivariable-adjusted mean of the total brain volume in the group with the lowest frequency of social contact was significantly lower compared to that in the group with the highest frequency (67.3% vs 67.8%), with a significant increasing trend across the groups (<i>p</i> value for trend <0.001). The white matter lesions volume increased significantly with lower frequency of social contact (0.30% in the lowest frequency vs 0.26% in the highest frequency group, <i>p</i> value for trend <0.001). Lower frequency of social contact was associated with smaller volumes in the temporal lobe, occipital lobe, cingulum, hippocampus, and amygdala (all <i>q</i> value of FDR correction <0.05). The relationships appeared to be partly mediated by depressive symptoms, which accounted for 15% to 29% of the observed associations.<h4>Discussion</h4>Lower frequency of social contact was associated with decreased total and cognitive function-related regional brain volumes. In addition, depressive symptoms partially explained the association in community-dwelling older people without dementia in Japan.

DOI： 10.1212/wnl.0000000000207602

DOI： 10.1212/WNL.0000000000207602

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掲載種別：研究論文（学術雑誌）  

<h4>Background</h4>Polypharmacy of additional psychotropics alongside the main treatment drug (antipsychotics in schizophrenia and antidepressants in major depressive disorder) is common in Japan. Our goal is to align psychotropic prescription in Japan with international standards, while reducing the differences between facilities. To achieve this goal, we aimed to compare prescriptions at the time of hospital admission and discharge.<h4>Methods</h4>Data on prescriptions at admission and discharge from 2016 to 2020 were collected. We divided the patients into four groups: (1) mono_mono group, monotherapy of the main drug at admission and discharge; (2) mono_poly group, monotherapy at admission and polypharmacy at discharge; (3) poly_poly group, polypharmacy at admission and discharge; and (4) poly_mono group, polypharmacy at admission and monotherapy at discharge. We compared the changes in dosage and number of psychotropics among the four groups.<h4>Results</h4>For both schizophrenia and major depressive disorder, the patients who received monotherapy with the main drug at admission were likely to receive main drug monotherapy at discharge and vice versa. For schizophrenia, the polypharmacy was prescribed more often in the mono_poly group than that in the mono_mono group. The prescription was not changed at all for more than 10% of the patients.<h4>Conclusions</h4>It is critical to avoid a polypharmacy regimen to ensure that guideline-compliant treatment is provided. We expect higher rates of monotherapy with the main drug after the EGUIDE lectures.<h4>Trial registration</h4>The study protocol was registered in the University Hospital Medical Information Network Registry (UMIN000022645).

DOI： 10.1186/s12888-023-04908-4

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記述言語：日本語   出版者・発行元：(公社)日本精神神経学会  

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記述言語：日本語   出版者・発行元：(公社)日本精神神経学会  

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記述言語：日本語   出版者・発行元：(公社)日本精神神経学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Although several guidelines recommend monotherapy with antipsychotics for the treatment of schizophrenia, patients who receive long-acting injectable antipsychotics (LAIs) are frequently treated with oral antipsychotics (OAPs). In the present study, we investigated the detailed use of psychotropic medications among patients throughout Japan with schizophrenia who received LAIs or OAPs. METHODS: The present study used data from the project for the Effectiveness of Guidelines for Dissemination and Education in psychiatric treatment from 94 facilities in Japan. The LAI group included patients who received any LAI, and the non-LAI group included patients who took only OAP medications at discharge. The participants of this study were 2518 schizophrenia patients (263 in the LAI group and 2255 in the non-LAI group) who received inpatient treatment and had prescription information at discharge between 2016 and 2020. RESULTS: This study revealed significantly higher rates of polypharmacy antipsychotics, number of antipsychotics, and chlorpromazine equivalents in the LAI group than in the non-LAI group. In contrast, the LAI group showed lower rate of concomitant use of hypnotic and/or antianxiety medication than the non-LAI group. CONCLUSIONS: Presenting these real-world clinical results, we want to encourage clinicians to keep monotherapy in mind for the treatment of schizophrenia, especially by reducing concomitant use of antipsychotics in the LAI group and reducing hypnotic and/or antianxiety medication in the non-LAI group.

DOI： 10.1097/JCP.0000000000001704

PubMed

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

Only 50% of patients with depression respond to the first antidepressant drug administered. Thus, biomarkers for prediction of antidepressant responses are needed, as predicting which patients will not respond to antidepressants can optimize selection of alternative therapies. We aimed to identify biomarkers that could predict antidepressant responsiveness using a novel data-driven approach based on statistical pattern recognition. We retrospectively divided patients with major depressive disorder into antidepressant responder and non-responder groups. Comprehensive gene expression analysis was performed using peripheral blood without narrowing the genes. We designed a classifier according to our own discrete Bayes decision rule that can handle categorical data. Nineteen genes showed differential expression in the antidepressant non-responder group (n = 15) compared to the antidepressant responder group (n = 15). In the training sample of 30 individuals, eight candidate genes had significantly altered expression according to quantitative real-time polymerase chain reaction. The expression of these genes was examined in an independent test sample of antidepressant responders (n = 22) and non-responders (n = 12). Using the discrete Bayes classifier with the <i>HERC5, IFI6,</i> and <i>IFI44</i> genes identified in the training set yielded 85% discrimination accuracy for antidepressant responsiveness in the 34 test samples. Pathway analysis of the RNA sequencing data for antidepressant responsiveness identified that hypercytokinemia- and interferon-related genes were increased in non-responders. Disease and biofunction analysis identified changes in genes related to inflammatory and infectious diseases, including coronavirus disease. These results strongly suggest an association between antidepressant responsiveness and inflammation, which may be useful for future treatment strategies for depression.

DOI： 10.1016/j.heliyon.2023.e13059

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掲載種別：研究論文（学術雑誌）  

<h4>Rationale & objective</h4>Chronic kidney disease, defined by albuminuria and/or reduced estimated glomerular filtration rate (eGFR), has been reported to be associated with brain atrophy and/or higher white matter lesion volume (WMLV), but there are few large-scale population-based studies assessing this issue. This study aimed to examine the associations between the urinary albumin-creatinine ratio (UACR) and eGFR levels and brain atrophy and WMLV in a large-scale community-dwelling older population of Japanese.<h4>Study design</h4>Population-based cross-sectional study.<h4>Setting & participants</h4>A total of 8,630 dementia-free community-dwelling Japanese aged greater than or equal to 65 years underwent brain magnetic resonance imaging scanning and screening examination of health status in 2016-2018.<h4>Exposures</h4>UACR and eGFR levels.<h4>Outcomes</h4>The total brain volume (TBV)-to-intracranial volume (ICV) ratio (TBV/ICV), the regional brain volume-to-TBV ratio, and the WMLV-to-ICV ratio (WMLV/ICV).<h4>Analytical approach</h4>The associations of UACR and eGFR levels with the TBV/ICV, the regional brain volume-to-TBV ratio, and the WMLV/ICV were assessed by using an analysis of covariance.<h4>Results</h4>Higher UACR levels were significantly associated with lower TBV/ICV and higher geometric mean values of the WMLV/ICV (<i>P</i> for trend = 0.009 and <0.001, respectively). Lower eGFR levels were significantly associated with lower TBV/ICV, but not clearly associated with WMLV/ICV. In addition, higher UACR levels, but not lower eGFR, were significantly associated with lower temporal cortex volume-to-TBV ratio and lower hippocampal volume-to-TBV ratio.<h4>Limitations</h4>Cross-sectional study, misclassification of UACR or eGFR levels, generalizability to other ethnicities and younger populations, and residual confounding factors.<h4>Conclusions</h4>The present study demonstrated that higher UACR was associated with brain atrophy, especially in the temporal cortex and hippocampus, and with increased WMLV. These findings suggest that chronic kidney disease is involved in the progression of morphologic brain changes associated with cognitive impairment.

DOI： 10.1016/j.xkme.2022.100593

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担当区分：責任著者   掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

DOI： 10.1002/pcn5.65

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その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/pcn5.65

掲載種別：研究論文（学術雑誌）  

DOI： 10.1186/s12991-022-00429-8

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

To disseminate, educate, and validate psychiatric clinical practice guidelines, the Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment (EGUIDE) project was launched in 2016. In this study, we investigated whether the web-based courses offered by this project would be as effective as the face-to-face courses. We analyzed and compared survey answers about overall participant satisfaction with the course and answers regarding clinical knowledge of schizophrenia and major depressive disorder between 170 participants who took the web-based courses in 2020 and 689 participants who took the face-to-face courses from 2016 to 2019. The web-based course participants completed the survey questions about satisfaction with the web-based courses. The web-based courses were conducted using a combination of web services to make it as similar as possible to the face-to-face courses. The degree of satisfaction assessed by the general evaluation of the web-based courses was higher than what was expected from the face-to-face courses. The degree of satisfaction was similar for the courses on schizophrenia and major depressive disorder. In addition, there were no significant differences in overall satisfaction and clinical knowledge between web-based and face-to-face courses. In conclusion, the web-based courses on clinical practice guidelines provided by the EGUIDE project were rated as more satisfying than the face-to-face course that the participants expected to take and no differences in the effectiveness of either course. The results suggest that, after the COVID-19 pandemic, it would be possible to disseminate this educational material more widely by adopting web-based courses additionally face-to-face courses.

DOI： 10.1002/npr2.12300

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIMS: The Guidelines for the Pharmacotherapy of Schizophrenia were established to improve the quality of medical care, and the EGUIDE project was conducted to train clinicians on guideline usage. A quality indicator (QI) was established to measure the prevalence of the guidelines, and a survey was conducted, which revealed a gap between the guidelines and actual clinical practice (evidence-practice-gap). The purpose of this study was to develop an individual fitness score (IFS) formula that expresses the degree to which prescribers adhere to the Guidelines for Pharmacological Therapy of Schizophrenia in a simple manner, and to determine the validity of this formula from a survey of the prescriptions of the EGUIDE project participants'. METHODS: To establish appropriate scores, members discussed the proposed formula and then voted on them. The IFS formula developed was set up so that antipsychotic monotherapy would be given 100 points, with points deducted if concomitant or adjunctive antipsychotic medications were used, and a minimum score of 0. To validate this formula, prescriptions of hospitalized schizophrenic patients at admission and at discharge were scored and compared. RESULT: IFS points vary and ranged from 0 to100. The average pre-admission score for all subjects was 45.6, and the average score at discharge was 54, those were significantly higher during discharge. CONCLUSIONS: We developed an IFS formula, a tool to easily visualize the degree to which current prescriptions conform to the guidelines for the pharmacological treatment of schizophrenia.

DOI： 10.1002/npr2.12293

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIM: We investigated the association of electroconvulsive therapy (ECT) with anxiolytic and sleep medication use in patients with major depressive disorder (MDD) and schizophrenia (SZ). METHODS: This nationwide observational study analyzed data from 3483 MDD inpatients and 6663 SZ inpatients. Patients with MDD and SZ were classified into those who underwent ECT during hospitalization and those who did not. A propensity score-matching method was performed to adjust for preadmission characteristics and clinical information, which were expected bias between the two groups. Rates of anxiolytic and sleep medication use at discharge were compared in the matched sample. RESULTS: 500 MDD patients were assigned to both groups. In the matched MDD sample, the rate of anxiolytic and sleep medication use at discharge was significantly lower in the ECT group than in the non-ECT group (64.9% vs. 75.8%, P = 1.7 × 10-4 ). In the ECT group, the rate of anxiolytic and sleep medication use at discharge was significantly lower than that prior to admission (64.9% vs. 73.2%, P = 1.2 × 10-14 ). 390 SZ patients were allocated. In the matched SZ sample, the ECT group was not significantly different from the non-ECT group in the rate of anxiolytics and sleep medications use at discharge (61.3% vs. 68.2%, P = 4.3 × 10-2 ). In the ECT group, the rate of anxiolytics and sleep medications use at discharge was significantly lower than that before admission (61.3% vs. 70.5%, P = 4.4 × 10-4 ), although this was not the primary outcome. CONCLUSION: Reduction of anxiolytic and sleep medication use may be considered positively when ECT is indicated for treatment of MDD.

DOI： 10.1111/pcn.13489

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Ovid Technologies (Wolters Kluwer Health)  

DOI： 10.1097/jcp.0000000000001604

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

DOI： 10.1002/pcn5.33

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その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/pcn5.33

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Existing meta-analytic evidence on bipolar mania treatment has revealed that augmentation therapy (AUG) with antipsychotics (AP) and mood stabilizers (MS) is more effective than monotherapy. However, the speed of the onset of treatment effects and subsequent changes in risk/benefit are unclear. METHODS: We searched the Cochrane CENTRAL, MEDLINE, and EMBASE databases until January 2021. Our primary outcomes were response and tolerability. We set three time points:1, 3, and 6 weeks after randomization. RESULTS: Seventeen studies compared AUG therapy and MS monotherapy (comparison 1), and eight studies compared AUG therapy and AP monotherapy (comparison 2). In comparison 1, AUG therapy resulted in significantly more responses than monotherapy, with an odds ratio (OR) of 1.45 (95% confidence interval [CI]: 1.17 to 1.80) at 3 weeks and 1.59 (95%CI: 1.28 to 1.99) at 6 weeks. Significant improvement was observed in the first week with a standardized mean difference (SMD) of -0.25 (95%CI: -0.38 to -0.12). In comparison 2, AUG therapy was significantly more effective than monotherapy, with an OR of 1.73 (95%CI: 1.25 to 2.40) at 3 weeks and 1.74 (95%CI: 1.11 to 2.73) at 6 weeks. Significant improvement was observed in the first week with an SMD of -0.23 (95%CI: -0.39 to -0.07). Regarding tolerability, there was no significant difference between AUG therapy and monotherapy at 3 and 6 weeks in both comparisons. CONCLUSIONS: Early AUG therapy should be considered, as it has shown efficacy from weeks 1 to 6, although attention to side effects is necessary for acute mania treatment.

DOI： 10.1093/ijnp/pyac050

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIM: While evidence-based antidepressant treatment is available for major depressive disorder, standard approaches for discontinuation of antidepressants after remission have not yet been established. Decision aids are structured clinical tools that facilitate shared decision-making between patients and healthcare providers. This study aimed to describe the development process and acceptability of decision aids for major depressive disorder following discontinuation of antidepressant treatment after remission. METHODS: We systematically developed a decision aids according to the International Patient Decision Aid Standards. First, a decision aids prototype was created using the results of a systematic review and meta-analysis previously conducted to identify the consequences of continuing and discontinuing antidepressant treatment. Second, a mixed-methods questionnaire (alpha acceptability testing) was administered to patients and healthcare providers to improve the decision aids prototype and develop it into a final version acceptable for clinical settings. RESULTS: Our decision aids consisted of a description of major depressive disorder, the option to continue or discontinue antidepressant treatment, the advantages and disadvantages of each option, the consequences of each option, and value clarification exercises for each option. The patients (n = 22) reported that the decision aids had acceptable language (91%), adequate information (91%), and a well-balanced presentation (95%). Healthcare providers (n = 20) provided favorable feedback. The final decision aids fulfilled all six International Patient Decision Aid Standards qualifying criteria. CONCLUSION: We successfully developed a decision aids for discontinuation of antidepressant treatment after remission, which could be used during the shared decision-making process. Further studies are needed to verify the effects of using the decision aids during the shared decision-making process.

DOI： 10.1002/npr2.12269

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The number of dementia patients is increasing worldwide, especially in Japan, which has the world's highest ageing population. The increase in the number of older people with dementia is a medical and socioeconomic problem that needs to be prevented, but the actual situation is still not fully understood. METHODS: Four cross-sectional studies on dementia were conducted in 1997, 2004, 2012, and 2016 for complete enumeration of all residents aged 65 years and older. We examined the secular trends in the prevalence of all-cause dementia, Alzheimer's disease (AD), vascular dementia (VaD), and other/unclassified dementia. RESULTS: The age-standardised prevalence of all-cause dementia significantly increased (4.5% in 1997, 5.7% in 2004, 5.3% in 2012, 9.5% in 2016; P for trend <0.05). Similar trends were observed for AD (1.7%, 3.0%, 2.5% and 4.9%, respectively; P for trend <0.05) and other/unclassified dementia (0.8%, 1.0%, 1.0% and 2.2%, respectively; P for trend <0.05), whereas no significant change in VaD was seen (2.1%, 1.8%, 1.8%, 2.4%, respectively; P for trend = 0.77). The crude prevalence of all-cause dementia and AD increased from 1997 to 2016 among participants aged 75-79 years and ≥85 years (all P for trend <0.05). Similar trends were observed for other/unclassified dementia among participants aged ≥80 years (all P for trend <0.05), but not in VaD. CONCLUSIONS: The prevalence of dementia has increased beyond the ageing of the population, suggesting that factors in addition to ageing are involved in the increase in the number of older people with dementia. To control the increase in the number of older people with dementia, elucidation of secular trends in the incidence, mortality, and prognosis of dementia as well as the factors that promote and protect against dementia, and development of preventive strategies are necessary.

DOI： 10.1111/psyg.12865

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Although clozapine is effective for treatment-resistant schizophrenia (TRS), the rate of clozapine prescription is still low. Although antipsychotic monotherapy is recommended in clinical practice guidelines, the rate of antipsychotic polypharmacy is still high. There is little evidence on whether a clozapine prescription influences changes in the rate of monotherapy and polypharmacy, including antipsychotics and other psychotropics. We therefore hypothesized that the rate of antipsychotic monotherapy in patients with TRS who were prescribed clozapine would be higher than that in patients with schizophrenia who were not prescribed clozapine. METHODS: We assessed 8306 patients with schizophrenia nationwide from 178 institutions in Japan from 2016 to 2019. We analyzed the psychotropic prescription data at discharge in patients diagnosed with TRS and with no description of TRS (ND-TRS) based on the diagnosis listed in the discharge summary. RESULTS: The rate of antipsychotic monotherapy in the TRS with clozapine group (91.3%) was significantly higher than that in the TRS without clozapine group (45.9%; p < 2.0 × 10 -16) and the ND-TRS without clozapine group (54.7%; p < 2.0 × 10 -16). The rate of antipsychotic monotherapy without any other concomitant psychotropics in the TRS with clozapine group (26.5%) was significantly higher than that in the TRS without clozapine group (12.6%; p = 1.1 × 10 -6) and the ND-TRS without clozapine group (17.0%; p = 5.9 × 10 -6). CONCLUSIONS: Clozapine prescription could be associated with a high rate of antipsychotic monotherapy. Patients will benefit from the correct diagnosis of TRS and thus from proper clozapine prescription.

DOI： 10.1093/ijnp/pyac036

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The Effectiveness of Guidelines for Dissemination and Education in psychiatric treatment (EGUIDE) project, which is a nationwide dissemination and implementation program for clinical practice guidelines (CPGs) in the field of psychiatry, is currently ongoing. In the current study, a subjective assessment of the participants in the EGUIDE programs was assessed using a questionnaire. Then, the relationships between the subjective assessment, the characteristics of the participants, and the clinical knowledge of the CPGs were evaluated. More than 90% of the participants gave a high rating for the components of content, recommendation, knowledge, skill, and adherence, but not for the component of confidence. A positive correlation was found between years of professional experience and the score of confidence. These results suggest that it may be necessary to apply the knowledge and skills of CPGs obtained in the education programs into practice to increase confidence in the proper use of psychiatric therapies based on CPGs.

DOI： 10.1002/npr2.12245

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

The Committee for Treatment Guidelines of Mood Disorders, Japanese Society of Mood Disorders, published a Japanese guideline for the treatment of late-life depression in 2020. Based on that guideline, the present guideline was developed and revised to incorporate the suggestions of global experts and the latest published evidence. In the diagnosis of late-life depression, it is important to carefully differentiate it from bipolar disorders, depressive states caused by physical and organic brain disease, drug effects, and dementia, and to determine the comorbidity between late-life depression and dementia. It is necessary to fully understand the clinical characteristics and psychosocial background of late-life depression, evaluate the patient's condition, and provide basic interventions based on these factors. Problem-solving therapy, reminiscence therapy/life review therapy, and behavioral activation therapy, and other forms of psychotherapy can reduce depressive symptoms. In terms of pharmacotherapy, newer antidepressants or non-tricyclic antidepressants are recommended for late-life depression, and it is recommended that the efficacy of least the minimal effective dosage should first be determined. Switching antidepressants and aripiprazole augmentation can be used to treatment-resistant therapy. Electroconvulsive therapy and repetitive transcranial magnetic stimulation have demonstrated usefulness for late-life depression. Exercise therapy, high-intensity light therapy, and diet therapy also show some effectiveness and are useful for late-life depression. Continuation therapy should be maintained for at least 1 year after remission.

DOI： 10.1111/pcn.13349

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その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/pcn.13349

記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: The relationship between alanine-glyoxylate aminotransferase 2 (AGXT2) single-nucleotide polymorphisms (SNPs) and diabetes mellitus (DM) has not been investigated. Therefore, we performed a case-control study to examine this relationship. METHODS: The study subjects included 2,390 Japanese men and women aged 34 to 88 years. In total, 190 cases were defined as having a fasting plasma glucose level ≥126 mg/dL, having a glycated hemoglobin ≥6.5% or currently using diabetic medication. The 2,200 remaining participants served as control subjects. RESULTS: Compared with study subjects with the CC genotype of AGXT2 SNP rs37369, those with the TT, but not CT, genotype had a significantly increased risk of DM: the adjusted odds ratio (OR) for the TT genotype was 1.83 (95% confidence interval [CI], 1.04 to 3.47). AGXT2 SNPs rs37370 and rs180749 were not significantly associated with the risk of DM. The CTA haplotype of rs37370, rs37369 and rs180749 was significantly positively associated with the risk of DM (crude OR, 1.25; 95% CI, 1.01 to 1.56), whereas the CCA haplotype was significantly inversely related to DM (crude OR, 0.53; 95% CI, 0.27 to 0.95). The multiplicative interaction between AGXT2 SNP rs37369 and smoking status with regard to the risk of DM was not significant (p=0.32 for interaction). CONCLUSIONS: This is the first study to show significant associations between AGXT2 SNP rs37369, the CTA haplotype, and the CCA haplotype and DM. No interaction with regard to the risk of DM was observed between rs37369 and smoking.

DOI： 10.1016/j.jcjd.2022.06.004

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Frontiers Media SA  

In several clinical guidelines for schizophrenia, long-term use of anticholinergic drugs is not recommended. We investigated the characteristics of the use of anticholinergics in patients with schizophrenia by considering psychotropic prescription patterns and differences among hospitals. A cross-sectional, retrospective prescription survey at the time of discharge was conducted on 2027 patients with schizophrenia from 69 Japanese hospitals. We examined the relations among psychotropic drug prescriptions regarding anticholinergic prescription. We divided the hospitals into three groups—low rate group (LG), medium rate group (MG), and high rate group (HG)—according to their anticholinergic prescription rates, and analyzed the relationship between anticholinergic prescription rates and antipsychotic prescription. Anticholinergic drugs were prescribed to 618 patients (30.5%), and the prescription rates were significantly higher for high antipsychotic doses, antipsychotic polypharmacy, and first-generation antipsychotics (FGAs) use. The anticholinergic prescription rate varied considerably among hospitals, ranging from 0 to 66.7%, and it was significantly higher in patients with antipsychotic monotherapy, antipsychotic polypharmacy, and normal and high doses of antipsychotics in HG than in those LG and MG. The anticholinergics prescription rate in patients with second-generation antipsychotic monotherapy in HG was also significantly higher than in those LG and MG; however, the difference was no longer significant in patients with FGA monotherapy. Conclusively, in addition to high antipsychotic doses, antipsychotic polypharmacy, and FGA use, hospital characteristics influence the prescribing of anticholinergic drugs.

DOI： 10.3389/fpsyt.2022.823826

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Clinical practice guidelines for schizophrenia and major depressive disorder have been published. However, these have not had sufficient penetration in clinical settings. We developed the Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment (EGUIDE) project as a dissemination and education programme for psychiatrists. AIMS: The aim of this study is to assess the effectiveness of the EGUIDE project on the subjective clinical behaviour of psychiatrists in accordance with clinical practice guidelines before and 1 and 2 years after participation in the programmes. METHOD: A total of 607 psychiatrists participated in this study during October 2016 and March 2019. They attended both 1-day educational programmes based on the clinical practice guidelines for schizophrenia and major depressive disorder, and answered web questionnaires about their clinical behaviours before and 1 and 2 years after attending the programmes. We evaluated the changes in clinical behaviours in accordance with the clinical practice guidelines between before and 2 years after the programme. RESULTS: All of the scores for clinical behaviours in accordance with clinical practice guidelines were significantly improved after 1 and 2 years compared with before attending the programmes. There were no significant changes in any of the scores between 1 and 2 years after attending. CONCLUSIONS: All clinical behaviours in accordance with clinical practice guidelines improved after attending the EGUIDE programme, and were maintained for at least 2 years. The EGUIDE project could contribute to improved guideline-based clinical behaviour among psychiatrists.

DOI： 10.1192/bjo.2022.44

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記述言語：日本語   出版者・発行元：(公社)日本精神神経学会  

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記述言語：日本語   出版者・発行元：(公社)日本精神神経学会  

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記述言語：日本語   出版者・発行元：(公社)日本精神神経学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

BACKGROUND: Although several guidelines indicate that daily pharmacotherapy is an important part of the treatment of schizophrenia and major depressive disorder, there are few reports regarding pro re nata (PRN) prescriptions. The purpose of this study is to clarify the characteristics of patients receiving psychotropic PRN prescription for the treatment of schizophrenia and major depressive disorder. METHOD: We used data from 'the effectiveness of guideline for dissemination and education in psychiatric treatment' (EGUIDE) project to evaluate the presence or absence of psychotropic PRN prescription at the time of discharge, the age and sex of patients receiving PRN prescription for each diagnosis, and the association between PRN prescription and regular daily psychotropics. RESULTS: The psychotropic PRN prescription ratio was 29.9% among 2617 patients with schizophrenia and 31.1% among 1248 patients with major depressive disorder at discharge. In schizophrenia, the psychotropic PRN prescription ratio was 21.6% for patients aged 65 years or older, which was lower than that of all other age groups. In major depressive disorder, the psychotropic PRN prescription ratio was 34.2% for female patients, which was significantly higher than that for male patients (25.5%). In schizophrenia, there was an association between psychotropic PRN prescription and regular use of multiple psychotropic medications. CONCLUSIONS: Psychotropic PRN prescription was less common in elderly patients with schizophrenia and more common in female patients with major depressive disorder. In schizophrenia, psychotropic PRN prescription led to polypharmacy of psychotropics. Further studies are needed to accumulate evidence and to provide education on appropriate PRN prescriptions.

DOI： 10.1016/j.ajp.2022.103007

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The decision to initiate clozapine treatment should be made on an individual basis and may be closely related to the early detection of treatment-resistant schizophrenia (TRS), although there is evidence that the early use of clozapine results in a better response to treatment. Therefore, we investigated the relationship between the examination rate of TRS and the prescription rate of clozapine. METHODS: After attending a 1-day educational program on schizophrenia based on the "Guidelines for the Pharmacological Treatment of Schizophrenia," we asked the participating facilities to submit records of whether or not TRS was evaluated for each patient. We calculated the clozapine prescription rate from the schizophrenic patients prescribed clozapine and all of the schizophrenic patients. Forty-nine facilities in 2017 were included in the study. RESULTS: There were dichotomous distributions in the examination rate of TRS and a non-normal distribution in the prescription rate of clozapine. There was a significant correlation between the prescription rate of clozapine and the examination rate of TRS (rs  = 0.531, P = 1.032 × 10-4 ). A significant difference was found in the prescription rate of clozapine between the three groups of facilities according to the examination rate of TRS. CONCLUSION: As a preliminary problem for the use of clozapine, in Japan, the examination rate of TRS varies, and there are many facilities that typically do not consider the possibility of TRS; this trend leads to a low rate of clozapine use. Clearly, further clinician training is needed for the early detection and appropriate management of TRS that includes an explanation of TRS and how to introduce clozapine therapy to patients and their families.

DOI： 10.1002/npr2.12218

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

AIM: Globally, evidence from short-term studies is insufficient for the guidelines to uniformly recommend a particular antipsychotic(s) for the maintenance treatment of schizophrenia. Therefore, long-term comprehensive evaluation of antipsychotics is required from a social rehabilitation perspective, especially for drugs that have not yet been studied. The Japan Useful Medication Program for Schizophrenia (JUMPs) is a large-scale, long-term naturalistic study to present pivotal 52-week data on the continuity of second-generation antipsychotics (SGA: aripiprazole, blonanserin, and paliperidone). METHODS: JUMPs was an open-label, three-arm, randomized, parallel-group, 52-week study. Enrolled patients had schizophrenia, were ≥20 years old, and required antipsychotic treatment or switched from previous therapy. The primary endpoint was treatment discontinuation rate over 52 weeks. Secondary outcomes included remission rate, social functioning, and quality-of-life scores [Personal and Social Performance Scale (PSP) and EuroQol-5 dimensions], and safety. RESULTS: In total, 251 patients received aripiprazole (n = 82), blonanserin (n = 85), or paliperidone (n = 84). The discontinuation rate (P = 0.9771) and remission rates (P > 0.05) over 52 weeks did not differ significantly between the three treatment groups. The discontinuation rates were 68.3%, 68.2%, and 65.5% in the aripiprazole, blonanserin, and paliperidone groups, respectively. Significant improvements (all P < 0.05) from baseline in PSP scores were observed at start of monotherapy, week 26, and week 52 in the overall cohort and blonanserin group and at week 26 in the aripiprazole group. The adverse event profile favored blonanserin. CONCLUSION: All three SGAs evaluated in this study showed similar treatment discontinuation rates in patients with chronic schizophrenia in Japan.

DOI： 10.1111/pcn.13304

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Dementia in patients with late-life mood disorders is clinically important. Objective: We aimed to investigate the prevalence of dementia in patients with late-life major depressive disorder (MDD) or bipolar disorder (BD) and to clarify the clinical characteristics associated with the diagnosis of dementia. Methods: The prevalence of dementia at hospital discharge and the clinical characteristics at hospitalization who are diagnosed with MDD or BD over 65 years of age, from the medical records of 684 patients who had been admitted from 2015 to 2020 were investigated. Results: A total of 66 patients with MDD (n = 50) and BD (n = 16) were analyzed. The prevalence of dementia was significantly higher in MDD than in BD (24.0% versus 0%; p = 0.026). The mean age at onset of MDD was significantly older in the MDD with dementia group than in the MDD without (76.9±6.3 years versus 62.2±14.0 years; p < 0.001). The rate of first depressive episode at this admission was significantly higher in the MDD with dementia group (91.7% versus 30.3%; p < 0.001). The diagnosis of dementia was significantly associated with lower scores for "insomnia early" (p = 0.019) and higher scores for "insight" (p = 0.049) on the 17-item Hamilton Depression Rating (HAMD-17) subscales and lower scores for "recall" (p = 0.003) on the MMSE subscales. Conclusion: The older age of first onset of depression, "insomnia early", "insight" and "recall" may be useful indicators for a diagnosis of dementia in late-life depression.

DOI： 10.3233/ADR-220052

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記述言語：日本語   出版者・発行元：(公社)日本精神神経学会  

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記述言語：日本語   出版者・発行元：(公社)日本精神神経学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Cryopreservation of whole blood is useful for DNA collection, and clinical and basic research. Blood samples in ethylenediaminetetraacetic acid disodium salt (EDTA) tubes stored at - 80 °C are suitable for DNA extraction, but not for high-quality RNA extraction. Herein, a new methodology for high-quality RNA extraction from human blood samples is described. Quickly thawing frozen whole blood on aluminum blocks at room temperature could minimize RNA degradation, and improve RNA yield and quality compared with thawing the samples in a 37 °C water bath. Furthermore, the use of the NucleoSpin RNA kit increased RNA yield by fivefold compared with the PAXgene Blood RNA Kit. Thawing blood samples on aluminum blocks significantly increased the DNA yield by ~ 20% compared with thawing in a 37 °C water bath or on ice. Moreover, by thawing on aluminum blocks and using the NucleoSpin RNA and QIAamp DNA Blood kits, the extraction of RNA and DNA of sufficient quality and quantity was achieved from frozen EDTA whole blood samples that were stored for up to 8.5 years. Thus, extracting RNA from frozen whole blood in EDTA tubes after long-term storage is feasible. These findings may help advance gene expression analysis, as well as biomarker research for various diseases.

DOI： 10.1038/s41598-021-96567-2

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/npr2.12193

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記述言語：日本語   出版者・発行元：日本うつ病学会・日本認知療法・認知行動療法学会  

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記述言語：日本語   出版者・発行元：日本うつ病学会・日本認知療法・認知行動療法学会  

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記述言語：日本語   出版者・発行元：日本うつ病学会・日本認知療法・認知行動療法学会  

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記述言語：日本語   出版者・発行元：日本うつ病学会・日本認知療法・認知行動療法学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media {LLC}  

A significant clinical issue encountered after a successful acute major depressive disorder (MDD) treatment is the relapse of depressive symptoms. Although continuing maintenance therapy with antidepressants is generally recommended, there is no established protocol on whether or not it is necessary to prescribe the antidepressant used to achieve remission. In this meta-analysis, the risk of relapse and treatment failure when either continuing with the same drug used to achieved remission or switching to a placebo was assessed in several clinically significant subgroups. The pooled odds ratio (OR) (±95% confidence intervals (CI)) was calculated using a random effects model. Across 40 studies (n = 8890), the relapse rate was significantly lower in the antidepressant group than the placebo group by about 20% (OR = 0.38, CI: 0.33-0.43, p < 0.00001; 20.9% vs 39.7%). The difference in the relapse rate between the antidepressant and placebo groups was greater for tricyclics (25.3%; OR = 0.30, CI: 0.17-0.50, p < 0.00001), SSRIs (21.8%; OR = 0.33, CI: 0.28-0.38, p < 0.00001), and other newer agents (16.0%; OR = 0.44, CI: 0.36-0.54, p < 0.00001) in that order, while the effect size of acceptability was greater for SSRIs than for other antidepressants. A flexible dose schedule (OR = 0.30, CI: 0.23-0.48, p < 0.00001) had a greater effect size than a fixed dose (OR = 0.41, CI: 0.36-0.48, p < 0.00001) in comparison to placebo. Even in studies assigned after continuous treatment for more than 6 months after remission, the continued use of antidepressants had a lower relapse rate than the use of a placebo (OR = 0.40, CI: 0.29-0.55, p < 0.00001; 20.2% vs 37.2%). The difference in relapse rate was similar from a maintenance period of 6 months (OR = 0.41, CI: 0.35-0.48, p < 0.00001; 19.6% vs 37.6%) to over 1 year (OR = 0.35, CI: 0.29-0.41, p < 0.00001; 19.9% vs 39.8%). The all-cause dropout of antidepressant and placebo groups was 43% and 58%, respectively, (OR = 0.47, CI: 0.40-0.55, p < 0.00001). The tolerability rate was ~4% for both groups. The rate of relapse (OR = 0.32, CI: 0.18-0.64, p = 0.0010, 41.0% vs 66.7%) and all-cause dropout among adolescents was higher than in adults. To prevent relapse and treatment failure, maintenance therapy, and careful attention for at least 6 months after remission is recommended. SSRIs are well-balanced agents, and flexible dose adjustments are more effective for relapse prevention.

DOI： 10.1038/s41380-020-0843-0

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

DOI： 10.1111/pcn.13143

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記述言語：日本語   出版者・発行元：(株)ワールドプランニング  

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記述言語：日本語   出版者・発行元：(公社)日本精神神経学会  

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記述言語：日本語   出版者・発行元：日本神経精神薬理学会・日本生物学的精神医学会・日本精神薬学会  

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記述言語：英語   出版者・発行元：日本神経精神薬理学会・日本生物学的精神医学会・日本精神薬学会  

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記述言語：日本語   出版者・発行元：日本神経精神薬理学会・日本生物学的精神医学会・日本精神薬学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

<h4>Background</h4>Guideline for Pharmacological Therapy for Schizophrenia was published by the Japanese Society of Neuropsychopharmacology in 2015. "Effectiveness of Guidelines for Dissemination and Education in psychiatric treatment (EGUIDE)" project aimed to standardize medical practice using quality indicators (QIs) as indices to evaluate the quality of medical practice. In this study, we have reported the quality indicator values of prescription before the beginning of the guideline lectures in the EGUIDE project to ascertain the baseline status of treating patients with schizophrenia.<h4>Methods</h4>A cross-sectional, retrospective case record survey was conducted, involving 1164 patients with schizophrenia at the time of discharge. We checked all types and dosage of psychotropic drugs.<h4>Results</h4>Forty-three percent of patients had antipsychotic polypharmacy, and substantial concomitant medication was observed (antidepressants; 8%, mood stabilizers: 37%, anxiolytics or hypnotics: 68%).<h4>Conclusions</h4>In the results obtained in this study, we plant to report changes in the effectiveness of education in the EGUIDE project near the future.

DOI： 10.1002/npr2.12122

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記述言語：英語   出版者・発行元：日本臨床精神神経薬理学会  

<p>Atypical antipsychotics cause hypoglycemia as a rare metabolic adverse effect in patients without diabetes. However, its mechanism is not sufficiently clarified. In the present case, a patient with schizophrenia presented with hypoglycemia induced by risperidone and olanzapine after becoming generally debilitated, but not by haloperidol. A complex interaction of serotonergic and adrenergic pathways with atypical antipsychotics may play a role in hypoglycemia. When prescribing atypical antipsychotics for patients, clinicians should be careful not only about the amount and character of the antipsychotics, but also the general status of the patients.</p>

DOI： 10.5234/cnpt.11.5

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記述言語：日本語   出版者・発行元：(株)星和書店  

一般的なうつ病の薬物療法のエビデンスでは高齢患者が対象から外されることが多いが、特に急速な高齢化を迎えている我が国においては、高齢うつ病患者の診療機会は増え続けており、高齢患者を含めた治療のエビデンスの集積が求められている。限定的なエビデンスではあるが、高齢うつ病においても一般成人とほぼ同様に抗うつ薬の有効性と安全性が示されているが、薬物動態や薬力学の加齢変化に基づく副作用の出現には十分注意する必要がある。一方、地域在住の高齢うつ病を対象としたリアルワールドの介入研究では精神療法や薬物療法を組み合わせたうつ病のケアマネージメントの有効性が示されている。(著者抄録)

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Schizophrenic patients resistant to antipsychotics are diagnosed as having treatment-refractory schizophrenia, and they are treated with clozapine. However, clozapine is sometimes combined with electroconvulsive therapy (ECT) if clozapine monotherapy fails. In this report, a severe treatment-refractory schizophrenic patient who did not respond to clozapine even with ECT, but who recovered with asenapine monotherapy, is presented. Asenapine, considered a serotonin spectrum dopamine modulator, is a new atypical antipsychotic with unique pharmacological features that is used not only for schizophrenia, but also for bipolar disorder. The unique features of asenapine may be effective for some treatment-refractory schizophrenic patients.

DOI： 10.9758/cpn.2019.17.4.559

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIM: Although treatment guidelines for pharmacological therapy for schizophrenia and major depressive disorder have been issued by the Japanese Societies of Neuropsychopharmacology and Mood Disorders, these guidelines have not been well applied by psychiatrists throughout the nation. To address this issue, we developed the 'Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment (EGUIDE)' integrated education programs for psychiatrists to disseminate the clinical guidelines. Additionally, we conducted a systematic efficacy evaluation of the programs. METHODS: Four hundred thirteen out of 461 psychiatrists attended two 1-day educational programs based on the treatment guidelines for schizophrenia and major depressive disorder from October 2016 to March 2018. We measured the participants' clinical knowledge of the treatment guidelines using self-completed questionnaires administered before and after the program to assess the effectiveness of the programs for improving knowledge. We also examined the relation between the participants' demographics and their clinical knowledge scores. RESULTS: The clinical knowledge scores for both guidelines were significantly improved after the program. There was no correlation between clinical knowledge and participant demographics for the program on schizophrenia; however, a weak positive correlation was found between clinical knowledge and the years of professional experience for the program on major depressive disorder. CONCLUSION: Our results provide evidence that educational programs on the clinical practices recommended in guidelines for schizophrenia and major depressive disorder might effectively improve participants' clinical knowledge of the guidelines. These data are encouraging to facilitate the standardization of clinical practices for psychiatric disorders.

DOI： 10.1111/pcn.12911

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1097/jcp.0000000000000998

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その他リンク： http://orcid.org/0000-0003-4409-3096

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Patients with schizophrenia or bipolar disorder have a high risk of developing type 2 diabetes. Aims: To identify predictive factors for hyperglycaemic progression in individuals with schizophrenia or bipolar disorder and to determine whether hyperglycaemic progression rates differ among antipsychotics in regular clinical practice. Method: We recruited 1166 patients who initially had normal or prediabetic glucose levels for a nationwide, multisite, l-year prospective cohort study to determine predictive factors for hyperglycaemic progression. We also examined whether hyperglycaemic progression varied among patients receiving monotherapy with the six most frequently used antipsychotics. Results: High baseline serum triglycerides and coexisting hypertension significantly predicted hyperglycaemic progression. The six most frequently used antipsychotics did not significantly differ in their associated hyperglycaemic progression rates over the 1-year observation period. Conclusions: Clinicians should carefully evaluate baseline serum triglycerides and coexisting hypertension and perform strict longitudinal monitoring irrespective of the antipsychotic used. Declaration of interest: The authors report no financial or other relationship that is relevant to the subject of this article. Relevant financial activities outside the submitted work are as follows. I.K. has received honoraria from Astellas, Chugai Pharmaceutical, Daiichi Sankyo, Dainippon Sumitomo Pharma, Eisai, Eli Lilly, Janssen Pharmaceutical, Kyowa Hakko Kirin, Meiji Seika Pharma, MSD, Nippon Chemiphar, Novartis Pharma, Ono Pharmaceutical, Otsuka Pharmaceutical, Pfizer, Tanabe Mitsubishi Pharma, Shionogi and Yoshitomiyakuhin; has received research/grant support from AbbVie GK, Asahi Kasei Pharma, Astellas, Boehringer Ingelheim, Chugai Pharmaceutical, Daiichi Sankyo, Dainippon Sumitomo Pharma, Eisai, Eli Lilly, GlaxoSmithKline, Kyowa Hakko Kirin, Meiji Seika Pharma, MSD, Novartis Pharma, Ono Pharmaceutical, Otsuka Pharmaceutical, Pfizer, Takeda Pharmaceutical, Tanabe Mitsubishi Pharma, Shionogi and Yoshitomiyakuhin; and is a member of the advisory boards of Dainippon Sumitomo Pharma and Tanabe Mitsubishi Pharma. Y.T. has received speaker's honoraria from Dainippon-Sumitomo Pharma, Otsuka, Meiji-Seika Pharma, Janssen Pharmaceutical, Daiichi-Sankyo Company, UCB Japan and Ono Pharmaceutical. K.U. has received honoraria from Dainippon Sumitomo Pharma, Eisai, Eli Lilly, Janssen Pharmaceutical, Kyowa Hakko Kirin, Meiji Seika Pharma, MSD, Takeda Pharmaceutical, Hisamitsu Pharmaceutical, Otsuka Pharmaceutical, Pfizer, Tanabe Mitsubishi Pharma, Shionogi and Yoshitomiyakuhin. B.Y. has received speaker's honoraria from Otsuka Pharmaceutical and Janssen Pharmaceutical. J. I. has received honoraria from Dainippon Sumitomo Pharma, Eli Lilly, Janssen Pharmaceutical, Meiji Seika Pharma, MSD, Novartis Pharma, Otsuka Pharmaceutical and Mochida Pharma.

DOI： 10.1192/bjo.2018.56

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：KOREAN COLL NEUROPSYCHOPHARMACOLOGY  

Objective: Donepezil is used to improve cognitive impairment of dementia with Lewy bodies (DLB). Visuo-spatial dysfunction is a well-known symptom of DLB. Non-verbal Raven's Colored Progressive Matrices (RCPM) were used to assess both visual perception and reasoning ability in DLB subjects treated with donepezil. Methods: Twenty-one DLB patients (mean age, 78.7±4.5 years) were enrolled. RCPM assessment was performed at the time of starting donepezil and within one year after starting donepezil. Results: There were significant improvements of RCPM in the total scores between one year donepezil treatment (p=0.013), in both Set A score (p=0.002) and Set AB score (p=0.015), but trend in the Set B score (p=0.083). Conclusion: Donepezil is useful for improving visuo-spatial impairment in DLB, but not for problem-solving impairment.

DOI： 10.9758/cpn.2017.15.3.243

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY  

ObjectiveImpairment of visual perception frequently occurs in Alzheimer's disease (AD) and can cause severe constraints in daily activities. The nonverbal Raven's Colored Progressive Matrices (RCPM) test consists of sets A, AB, and B and is easily performed in a short time to evaluate both visual perception and reasoning ability. The purpose of this study was to evaluate the neural basis of visual perception and reasoning ability in patients with AD using RCPM and single-photon emission computed tomography (SPECT).
MethodsFifty patients who fulfilled the National Institute on Aging/Alzheimer's Association criteria for probable AD dementia were examined with RCPM and SPECT. All SPECTs were performed using N-isopropyl-p-[I-123]-iodoamphetamine. A multiple regression model was used to perform multivariate analyses of the relationships between regional cerebral blood flow (rCBF) and RCPM scores.
ResultsThere was a significant positive correlation between RCPM total score and rCBF in the inferior parietal lobes bilaterally, the right inferior temporal gyrus, and the right middle frontal gyrus. Set A was positively correlated with rCBF in the right temporal and right parietal lobes. Set AB was positively correlated with rCBF in the right temporal, right parietal, and right frontal lobes. Set B was positively correlated with rCBF in the right parietal and right frontal lobes.
ConclusionOur findings suggest that deteriorations of specific brain regions are associated with dysfunction of visual perception and reasoning ability in AD. RCPM is another informative assessment scale of cognition for use in patients with AD. Copyright (c) 2016 John Wiley & Sons, Ltd.

DOI： 10.1002/gps.4481

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

Background: Previous studies of patients with bipolar disorder (BD) using magnetic resonance spectroscopy (MRS) have shown neurophysiological abnormalities related to the glutamate (Glu)-glutamine (Gin) cycle, membrane turnover, and neuronal integrity, although the results were neither consistent nor conclusive. Recently it has been reported the Gln/Glu ratio is the most useful index, quantifying neuronal-glial interactions and the balance of glutamatergic metabolites In this MRS study, we elucidated the abnormalities of metabolites in a larger sample of patients with BD with a high-field MRI system.
Methods: Sixty-two subjects (31 patients with BD and 31 healthy controls [HC]) underwent 3T proton MRS (1H-MRS) of the anterior cingulate cortex (ACC) and left basal ganglia (1tBG) using a stimulated echo acquisition mode (STEAM) sequence.
Results: After verifying the data quality, 20 patients with BD and 23 age- and gender-matched HCs were compared using repeated-measures analysis of covariance (ANCOVA). Compared to the HC group, the BD group showed increased levels of Gln, creatine (Cr), N-acetyl aspartate (NAA), choline (Cho), and an increased ratio of Gln to Glu in the ACC, and increased Gln and Cho in the 1tBG. These findings remained after the participants with BD were limited to only euthymic patients. After removing the influence of lithium (Li) and sodium valproate (VPA), we observed activated glutamatergic neurotransmission in the ACC but not in the 1tBG.
Limitations: The present findings are cross-sectional and metabolites were measured in only two regions.
Conclusions: Our results support a wide range of metabolite changes in patients with BD involved in glutamatergic neurotransmission, membrane turnover, and neuronal integrity. Moreover, the elevation of Gln/Glu ratio suggested that hyperactivity of glutamatergic neurotransmission in the ACC is a disease marker for BD.

DOI： 10.1016/j.jad.2016.08.046

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：DOVE MEDICAL PRESS LTD  

PURPOSE: Recently, we could distinguished patients with major depressive disorder (MDD) from nonpsychiatric controls with high accuracy using a panel of five gene expression markers (ARHGAP24, HDAC5, PDGFC, PRNP, and SLC6A4) in leukocyte. In the present study, we examined whether this biological test is able to discriminate patients with MDD from those without MDD, including those with schizophrenia and bipolar disorder. PATIENTS AND METHODS: We measured messenger ribonucleic acid expression levels of the aforementioned five genes in peripheral leukocytes in 17 patients with schizophrenia and 36 patients with bipolar disorder using quantitative real-time polymerase chain reaction (PCR), and we combined these expression data with our previous expression data of 25 patients with MDD and 25 controls. Subsequently, a linear discriminant function was developed for use in discriminating between patients with MDD and without MDD. RESULTS: This expression panel was able to segregate patients with MDD from those without MDD with a sensitivity and specificity of 64% and 67.9%, respectively. CONCLUSION: Further research to identify MDD-specific markers is needed to improve the performance of this biological test.

DOI： 10.2147/NDT.S120038

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記述言語：英語   出版者・発行元：OXFORD UNIV PRESS  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：TAYLOR & FRANCIS INC  

Aberrant DNA methylation in the blood of patients with major depressive disorder (MDD) has been reported in several previous studies. However, no comprehensive studies using medication-free subjects with MDD have been conducted. Furthermore, the majority of these previous studies has been limited to the analysis of the CpG sites in CpG islands (CGIs) in the gene promoter regions. The main aim of the present study is to identify DNA methylation markers that distinguish patients with MDD from non-psychiatric controls. Genome-wide DNA methylation profiling of peripheral leukocytes was conducted in two set of samples, a discovery set (20 medication-free patients with MDD and 19 controls) and a replication set (12 medication-free patients with MDD and 12 controls), using Infinium HumanMethylation450 BeadChips. Significant diagnostic differences in DNA methylation were observed at 363 CpG sites in the discovery set. All of these loci demonstrated lower DNA methylation in patients with MDD than in the controls, and most of them (85.7%) were located in the CGIs in the gene promoter regions. We were able to distinguish patients with MDD from the control subjects with high accuracy in the discriminant analysis using the top DNA methylation markers. We also validated these selected DNA methylation markers in the replication set. Our results indicate that multiplex DNA methylation markers may be useful for distinguishing patients with MDD from non-psychiatric controls.

DOI： 10.1080/15592294.2014.1003743

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記述言語：英語   出版者・発行元：KOREAN COLL NEUROPSYCHOPHARMACOLOGY  

Although the effectiveness of medication in the treatment of anorexia nervosa is uncertain, atypical antipsychotics such as olanzapine and risperidone have been used empirically for decades, we describe the case of a 10-year-old boy with anorexia nervosa in whom remarkable improvement was seen following the administration of risperidone or risperidone long-acting-injection and deterioration when these agents were ceased. Because this is, to the best of our knowledge, the first report describing the usefulness of risperidone long-acting injection for adolescent anorexia nervosa.

DOI： 10.9758/cpn.2014.12.1.65

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記述言語：日本語   出版者・発行元：日本生物学的精神医学会  

うつ病の基盤には脳の機能変調が存在し，その影響は神経内分泌系，神経免疫系，自律神経系を通して全身に及んでいる。これらを利用したバイオマーカーの探索はこれまでも数多い。デキサメサゾン抑制試験や脳由来神経栄養因子（BDNF）濃度などは最も注目されてきた。しかし，いずれも臨床応用可能な感度と特異度が達成できていない。近年の革新的な方法論の進歩はこの現状を打破する可能性をもたらした。血中タンパク質，mRNA 発現量， DNA メチル化修飾あるいはマイクロ RNA 量などを網羅的に解析することが可能になり，複数測定値を組み合わせたバイオマーカーの開発が進められている。2013 年 6 月に京都で開催された世界生物学的精神医学会議におけるシンポジウムにおいて，血液をサンプルとする気分障害の診断マーカー研究の最新状況を，米国，イスラエル，日本からの 4 名の演者が発表した。いずれも斬新な研究であり，近い将来の診断マーカーとしての臨床応用を期待させるものである。

DOI： 10.11249/jsbpjjpp.25.2_79

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記述言語：英語   出版者・発行元：ELSEVIER SCI LTD  

DOI： 10.1016/j.parkreldis.2013.04.027

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.parkreldis.2013.04.027

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：HUMANA PRESS INC  

Schizophrenia (SCZ) is a complex psychiatric disease with a lifetime morbidity rate of 0.5-1.0 %. To date, aberrant DNA methylation in SCZ has been reported in several studies. However, no comprehensive studies using medication-free subjects with SCZ have been conducted. In addition, most of these studies have been limited to the analysis of the CpG sites in CpG islands (CGIs) in the gene promoter regions, so little is known about the DNA methylation signatures across the whole genome in SCZ. Genome-wide DNA methylation profiling (485,764 CpG sites) of peripheral leukocytes was conducted in the first set of samples (24 medication-free patients with SCZ and 23 non-psychiatric controls) using Infinium HumanMethylation450 Beadchips. Second, a monozygotic twin study was performed using three pairs of monozygotic twins that were discordant for SCZ. Finally, the data from these two independent cohorts were compared. A total of 234 differentially methylated CpG sites that were common between these two cohorts were identified. Of the 234 CpG sites, 153 sites (65.4 %) were located in the CGIs and in the regions flanking CGIs (CGI: 40.6 %; CGI shore: 13.3 %; CGI shelf: 11.5 %). Of the 95 differently methylated CpG sites in the CGIs, most of them were located in the promoter regions (promoter: 75.8 %; gene body: 14.7 %; 3'-UTR: 2.1 %). Aberrant DNA methylation in SCZ was identified at numerous loci across the whole genome in peripheral leukocytes using two independent sets of samples. These findings support the notion that altered DNA methylation could be involved in the pathophysiology of SCZ.

DOI： 10.1007/s12017-012-8198-6

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その他リンク： http://orcid.org/0000-0003-4409-3096

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER IRELAND LTD  

The epithelial membrane protein 1 (EMP1) plays a role in neuronal differentiation and neurite outgrowth, which are involved in the pathogenesis of major depressive disorder (MDD). We sought to determine whether the EMP1 gene is implicated in MDD. We determined the mRNA expression levels of the EMP1 gene in peripheral-blood leukocytes of patients and control subjects (n = 27 each). Next, we performed case-control association analyses (MDD, n = 182: controls, n = 350) in the Japanese population. The level of expression of the EMP1 mRNA was significantly lower in medication-free patients compared with control subjects (P&lt;0.001). The association analysis revealed an absence of association between the polymorphisms studied and MDD, whereas a gender-specific association was observed between male controls and male patients for marker rs7315725 (permutation P = 0.039). Our results suggest that the EMP1 gene may be implicated in the pathophysiology of MDD in the Japanese population. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.neulet.2010.12.001

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：HUMANA PRESS INC  

Disrupted-in-schizophrenia 1 (DISC1), a known genetic risk factor for schizophrenia (SZ) and major depressive disorder (MDD), interacts with several proteins and some of them are reported to be genetically associated with SZ. Pericentrin (PCNT) also interacts with DISC1 and recently single-nucleotide polymorphisms (SNPs) within the PCNT gene have been found to show significant associations with SZ and MDD. In this study, case-controlled association analysis was performed to determine if the PCNT gene is implicated in SZ. Nine SNPs were analyzed in 1,477 individuals (726 patients with SZ and 751 healthy controls). No significant difference was observed between the controls and the patients in allelic frequencies or genotypic distributions of eight SNPs. Although allelic distribution of rs11702684 was different between the two groups (P = 0.042), the difference did not reach statistical significance after permutation correction for multiple comparisons. In the haplotypic analysis, we could not find any significant association in our subjects, either. This gene may not play a major role independently in the etiology of SZ in the Japanese population.

DOI： 10.1007/s12017-009-8106-x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

Gamma-amino butyric acid (GABA) is thought to play a role in the pathophysiology of schizophrenia. High magnetic held proton magnetic resonance spectroscopy ((1)H-MRS) provides a reliable measurement of GABA in specific regions of the brain. This Study measured GABA concentration in the anterior cingulate cortex (ACC) and ill the left basal ganglia (ItBG) in 38 patients with chronic schizophrenia and 29 healthy control subjects.
There was no significant difference in GABA concentration between the schizophrenia patients and the healthy controls in either the ACC (1.36 +/- 0.45 mmol/l in schizophrenia patients and 1.52 +/- 0.54 mmol/l in control Subjects) or the ItBG (1.13 +/- 0.26 mmol/l ill schizophrenia patients and 1.18 +/- 0.20 mmol/l in control Subjects). Among the right handed schizophrenia patients, the GABA concentration in the ItBG was significantly higher in patients talking typical antipsychotics (1.25 +/- 0.24 mmol/l) than in those taking atypical antipsychotics (1.03 +/- 0.24 mmol/l, p = 0.026). In the ACC, the GABA concentration was negatively correlated with the close of the antipsychotics (rs = -0.347, p = 0.035). In the ItBG, the GABA concentration was positively correlated with the dose of the anticholinergics (rs = 0.403, p = 0.015).
To the best of four knowledge, this is the first Study to have directly measured GABA concentrations in schizophrenia patients using (1)H-MRS. Out, results suggest that there are no differences in GABA concentrations in the ACC or the ItBG of schizophrenia patients compared to healthy controls. Antipsychotic medication may cause changes in GABA concentration, and atypical and typical antipsychotics may have differing effects. It is possible that medication effects conceal inherent differences in GABA concentrations between schizophrenia patients and healthy controls. (C) 2009 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.schres.2009.11.011

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掲載種別：研究論文（学術雑誌）  

The phosphodiesterase 4B (PDE4B) interacts with disrupted-inschizophrenia 1 (DISC1), which is a knowngenetic risk factor for schizophrenia, bipolar disorder and major depressive disorder (MDD). PDE4B is also important in the regulation of cAMP signaling, a second messenger implicated in learning, memory, and mood. In this study, we determined mRNA expression levels of the PDE4B gene in the peripheral blood leukocytes of patients with MDD and control subjects (n = 33, each). Next we performed two-stage case-controlled association analyses (first set; case = 174, controls = 348; second set; case = 481, controls = 812) in the Japanese population to determine if the PDE4B gene is implicated in MDD. In the leukocytes, a significantly higher expression of the PDE4B mRNA was observed in the drug-naïve MDD patients compared with control subjects (P<0.0001) and the expression of the MDD patients significantly decreased after antidepressant treatment (P = 0.030). In the association analysis, we observed significant allelic associations of four SNPs (the most significant, rs472952; P = 0.002) and a significant haplotypic association (permutation P = 0.019) between the PDE4B gene and MDD in the first-set samples. However, we could not confirm these significant associations in the following independent second-set of samples. Our results suggest that the PDE4B gene itself does not link to MDD but the elevated mRNA levels of PDE4B might be implicated in the pathophysiology of MDD. © 2008 Wiley-Liss, Inc.

DOI： 10.1002/ajmg.b.30852

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記述言語：英語   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

DOI： 10.1097/YPG.0b013e32832a5030

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：CMA-CANADIAN MEDICAL ASSOC  

Background: Pericentrin (PCNT) interacts with disruption-in-schizophrenia 1 (DISC1), a known genetic risk factor for schizophrenia, bipolar disorder and major depressive disorder (MDD). We sought to determine whether the PCNT gene is implicated in MDD. Methods: We performed case-control association analyses in the Japanese population. We analyzed 9 single nucleotide polymorphisms (SNPs) in 173 patients with MDD and 348 healthy controls. Results: We found a significant allelic association between 3 SNPs (rs3788265, rs2073376 and rs2073380) of the PCNT gene and MDD (p = 0.006, 0.005 and 0.021, respectively). After correction for multiple testing, 2 SNPs (rs3788265 and rs2073376) retained significant allelic associations with MDD. In addition, we found a significant association between the 2 marker haplotypes (r3788265 and rs2073376) and MDD (permutation p = 0.011). Limitations: Our sample was small and comprised only Japanese participants. In addition, owing to the late onset of MDD, it is possible that the disorder will develop in at least some participants in our control group. Finally, we did not show how SNPs of the PCNT gene alter its function. Conclusion: Our results suggest that genetic variations in the PCNT gene may play a significant role in the etiology of MDD in the Japanese population.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：CMA-CANADIAN MEDICAL ASSOC  

Background: Pericentrin (PCNT) interacts with disruption-in-schizophrenia 1 (DISC1), a known genetic risk factor for schizophrenia, bipolar disorder and major depressive disorder (MDD). We sought to determine whether the PCNT gene is implicated in MDD. Methods: We performed case-control association analyses in the Japanese population. We analyzed 9 single nucleotide polymorphisms (SNPs) in 173 patients with MDD and 348 healthy controls. Results: We found a significant allelic association between 3 SNPs (rs3788265, rs2073376 and rs2073380) of the PCNT gene and MDD (p = 0.006, 0.005 and 0.021, respectively). After correction for multiple testing, 2 SNPs (rs3788265 and rs2073376) retained significant allelic associations with MDD. In addition, we found a significant association between the 2 marker haplotypes (r3788265 and rs2073376) and MDD (permutation p = 0.011). Limitations: Our sample was small and comprised only Japanese participants. In addition, owing to the late onset of MDD, it is possible that the disorder will develop in at least some participants in our control group. Finally, we did not show how SNPs of the PCNT gene alter its function. Conclusion: Our results suggest that genetic variations in the PCNT gene may play a significant role in the etiology of MDD in the Japanese population.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

A change in the glutamatergic system is thought to play an important role in the pathophysiology of schizophrenia. The aim of this study was to investigate the changes in metabolites, including glutamate (Glu), in the anterior cingulate cortex (ACC) and the left basal ganglia (ItBG) of patients with chronic schizophrenia using proton magnetic resonance spectroscopy (H-1-MRS). In addition, since gender differences in this illness were known, we examined the effects of gender on these metabolites.
The H-1-MRS was performed on the ACC and ItBG of 30 patients with schizophrenia and 25 healthy individuals who acted as the control group. The levels of Glu, glutamine (Gln), creatine plus phosphocreatine (Cre), myo-inositol (ml), N-acetylaspartate (NAA), and choline-containing compounds (Cho) were measured.
Two-way analysis of variance revealed that the illness significantly affected the levels of Glu and ml in the ACC; both metabolites were lower in the patients with schizophrenia as compared to the control subjects. The results also revealed that gender significantly affected the level of Gln in the ACC and the levels of Cre and NAA in the ItBG; the level of Gln in the ACC were higher in male subjects versus female subjects, whereas Cre and NAA levels in the ItBG were lower in male subjects as compared to female subjects.
These results confirmed a change in the glutamatergic system and suggested an involvement of ml in the pathophysiology of schizophrenia. (C) 2008 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.schres.2008.11.014

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掲載種別：研究論文（学術雑誌）  

The phosphodiesterase 4B (PDE4B) gene is located at 1p31, a susceptibility region for schizophrenia (SZ). Moreover, PDE4B interacts with DISC1, which is a known genetic risk factor for SZ. Recently, it was reported that the PDE4B gene is associated with SZ in Caucasian and African American populations. In this study, case-controlled association analyses were performed in the Japanese population to determine if the PDE4B gene is implicated in SZ. Thirteen single nucleotide polymorphisms (SNPs) were analyzed in 444 schizophrenic patients and 452 control subjects. Three SNPs (rs2180335, rs910694 and rs472952) were significantly associated with SZ after applying multiple test correction (p = 0.039, 0.004 and 0.028). In addition, a significant association was found between specific haplotypes (rs2180335 and rs910694) and SZ (permutation p = 0.001). Our result suggests that variations at the PDE4B locus may play a significant role in the etiology of SZ in the Japanese population. © 2008 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jpsychires.2008.01.013

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

Aim: In recent years, greater attention has been given to quality of life (QOL) in schizophrenia and several studies reported that negative and depressive symptoms and cognitive dysfunction are related to patient QOL. But because a variety of QOL measures have been used in the previous studies, there seems to be no unanimous predictors for subjective and objective QOL. The purpose of the present study was to elucidate the relationship between clinical variables and subjective and objective QOL in outpatients with schizophrenia, using schizophrenia disease-specific QOL measures. Particular attention was paid to cognitive function as a predictor of QOL.
Methods: Schizophrenia symptoms of the Positive and Negative Syndrome Scale (PANSS) were divided into five factors: positive factor, negative factor, cognitive factor, emotional discomfort, and hostility. The study sample consisted of 84 schizophrenia outpatients. Subjective and objective QOL were assessed with Schizophrenia Quality of Life Scale (SQLS) and the Quality of Life Scale (QLS), respectively.
Results: Subjective QOL correlated significantly with emotional discomfort, positive factor, negative factor, extrapyramidal symptoms and cognitive factor, while objective QOL correlated with negative factor, cognitive factor, emotional discomfort, extrapyramidal symptoms, and dose of antipsychotics. Total score and three of four subscales in the QLS correlated significantly with cognitive factor, while cognitive factor had a significant correlation with only one of three scales of SQLS. Stepwise regression showed that subjective QOL was significantly predicted by emotional discomfort and extrapyramidal symptoms, while negative factor was the most important predictor of objective QOL.
Conclusion: Cognitive dysfunction had a greater influence on objective QOL than subjective QOL. Treating depressive and negative symptoms and extrapyramidal symptoms might contribute to enhanced subjective and objective QOL.

DOI： 10.1111/j.1440-1819.2008.01818.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

TGFBR2 gene is a tumor suppressor gene located at chromosome 3p22, and the locus is reported to be linked with schizophrenia susceptibility. According to the previous studies, a reduced incidence of cancer is observed in schizophrenic patients compared with the general population and tumor suppressor genes may be associated with schizophrenia. We measured the mRNA expression of TGFBR2 gene in the peripheral leukocytes from 19 medication-free schizophrenics and 25 medication-free major depressive patients compared with age- and sex-matched control subjects using a quantitative real-time PCR method. We also followed up the TGFBR2 mRNA expression levels from 13 schizophrenics after several weeks - antipsychotic treatments. The TGFBR2 mRNA levels of medication free schizophrenics were significantly higher than those of control subjects and decreased to almost the same level as controls after antipsychotic treatment. On the other hand, the TGFBR2 mRNA levels of medication-free major depressive patients were not significantly different from controls. In genetic studies, we failed to find any association between the TGFBR2 gene and schizophrenia with 10 SNPs of TGFBR2 gene in Japanese subjects (279 subjects each) and there was no significant difference with haplotype analysis, either. Our results suggest that the TGFBR2 gene itself does not link to schizophrenia but that the TGFBR2 mRNA levels in the peripheral leukocytes may be a potential state marker for schizophrenia. (c) 2007 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jpsychires.2007.04.002

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その他リンク： http://orcid.org/0000-0003-4409-3096

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER IRELAND LTD  

There have been several evidences that the mRNA expressions in the peripheral leukocytes may indicate not only physical but also psychological states. The purpose of this study is whether the mRNA expressional changes in the leukocytes are related to the mental states across the menstrual cycle in reproductive healthy female subjects. Thirty-eight female subjects (22.4 +/- 11.4 year-old) were participated in this study at three menstruation cycle periods (menstrual, follicular and luteal phase). The FKBP5 (FK506-binding protein gene), SERT (serotonin transporter gene) and COMT (catechol-o-methyltransferase gene) mRNA expressions in the leukocytes were determined with hormonal data. The psychological changes were assessed with self-rating hospital anxiety and depression scale (HADS). Only one thirds of subjects (n = 12) had regular menstrual cycles during the experiment. So we analyzed the data from these 12 subjects. The anxiety score of each subject was changed across the menstrual cycle (Friedman test: P &lt; 0.05). The FKBP5 mRNA expression was significantly lower in the follicular phase than in the other phases but no changes were seen in either SERT or COMT mRNA expressions among the phases. In conclusion, there are differences of HADS anxiety score and FKBP5 mRNA expression in the leukocytes across the menstrual cycle but there is no correlation between anxiety scores and FKBP5 mRNA. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.neulet.2008.01.039

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その他リンク： http://orcid.org/0000-0003-4409-3096

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER IRELAND LTD  

The purpose of the present Study is to investigate the relationships among subjective and objective quality of life (QOL), and levels of life skills, and their clinical determinants in outpatients with schizophrenia by using schizophrenia disease-specific QOL measures.. Data collected from 64 Outpatients were analyzed. Subjective QOL was measured with the Schizophrenia Quality of Life Scale (SQLS) and objective QOL with the Quality of Lire Scale (QLS). Patients' family members completed the Life Skills Profile (LSP). Clinical symptoms were also assessed with several scales including the Brief Psychiatric Rating Scale (BPRS) and the Calgary Depression Scale for Schizophrenia (CDSS). Only the motivation/energy scale, but lot the Other scales of the SQLS, correlated with the QLS. The LSP rated by the family showed significant correlations with both the SQLS and the QLS. The CDSS score predicted each scale of the SQLS, and the BPRS negative symptoms score predicted the QLS. The LSP was predicted by the BPRS negative symptoms score and the CDSS score independently. These results indicate that the Patient's QOL could be predicted by the life: skills measured by a family member and Suggest that active treatment for depressive and negative symptoms might be recommended to improve the patient's QOL and life skills. (c) 2006 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.psychres.2006.05.017

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その他リンク： http://orcid.org/0000-0003-4409-3096

DOI： 10.1016/j.schres.2007.10.032

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

Accumulating evidence suggests that both homocysteine metabolism and monoaminergic neurotransmitter systems are important in schizophrenia pathology. We hypothesized that the gene PNPO (pyridoxine 5'-phospliatase oxidase gene) might be a candidate for susceptibility to schizophrenia because PNPO encodes pyridoxamine 5'-phosphate oxidase (EC 1.4.3.5), a rate-limiting enzyme in pyridoxal 5'-phosphate (PLP, vitamin B-6) Synthesis. PLP is a metabolically-active form of vitamin B-6 and thus, is required as a co-factor for enzymes involved in both homocysteine metabolism and synthesis of neurotransmitters such as catecholamine. We examined 8 single nucleotide polymorphisms (SNPs) in PNPO and its 5'-flanking regions in 359 schizophrenia patients and 582 control subjects. Four marker regions of PNPO showed significant levels of allelic associations with schizophrenia (the highest was rs2325751, P=0.004). In addition, the haplotype case-control study revealed a significant association (permutation P&lt;0.00001) between PNPO and schizophrenia. These findings suggest that variations in PNPO may contribute to overall genetic risk for schizophrenia in the Japanese population. (C) 2007 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.schres.2007.08.004

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その他リンク： http://orcid.org/0000-0003-4409-3096

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER IRELAND LTD  

PDLIM5 modulates neuronal calcium signaling, co-localizes with synaptic vesicles of neurotransmitters and positive association between its gene and schizophrenia was reported but its relation is still ambiguous. The differential expression of the PDLIM5 gene both in the brain and in the lymphoblasts has been found in schizophrenia compared to control subjects. In this study, we measured the expression level of the PDLIM5 gene transcripts in the peripheral leukocytes from 19 medication-free and 21 chronically medicated schizophrenic patients as well as age- and sex-matched control subjects using a quantitative real-time PCR method. The mRNA levels of the PDLIM5 gene in the leukocytes of medication-free schizophrenic patients were significantly higher than those of control subjects. On the other hand, our group has previously shown that its mRNA expression in the leukocytes of medication-free major depressive patients was significantly lower compared with controls. There was no difference in the PDLIM5 mRNA levels between chronic schizophrenic patients with antipsychotic medication and their controls. Further, we failed to find any genetic association between the PDLIM5 gene and schizophrenia with six single nucleotide polymorphics (SNPs) of the PDLIM5 gene in Japanese subjects (279 subjects each) and there was no significant relation between PDLIM5 gene and schizophrenia with the haplotype analysis (P=0.48), either. We suggest that the higher expression levels of the PDLIM5 mRNA in the peripheral leukocytes may be a candidate marker for medication-free schizophrenic patients. (c) 2007 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.neulet.2007.01.018

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その他リンク： http://orcid.org/0000-0003-4409-3096

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER WIEN  

Catechol-O-methyltransferase (COMT) gene is one of the candidate genes for schizophrenia because it codes an enzyme that participates in the metabolic inactivation of dopamine and noradrenaline and a limiting factor of dopamine metabolism in the prefrontal cortex. COMT gene lies on chromosome 22q11.2, which has been associated with schizophrenia susceptibility. A single-nucleotide polymorphism of COMT gene at position 108/158 results in an amino acid substitution from valine (val) to methionine (met), which modifies its enzymatic activity and may change the brain morphology and expressional behaviors. On the other hand, brain-derived neurotrophic factor (BDNF) plays a critical role in the development of mesolimbic dopaminergic- related systems. BDNF also contains a functional single-nucleotide polymorphism at codon 66 (Val66Met) of its prodomain and this polymorphism is responsible for schizophrenia susceptibility. In this study, we first investigated the relationship between COMT Val108/158Met polymorphism and age at onset as well as levels of clinical symptoms in 158 of chronic schizophrenia inpatients and then we investigated the gene-by-gene interaction between COMT Val108/158Met polymorphism and BDNF Val66Met polymorphism with age- and sex-matched control subjects (n = 318). We concluded that the COMT Val108/158Met polymorphism was not related to either the onset at age or the levels of clinical symptoms after long-term antipsychotic treatment in schizophrenia.

DOI： 10.1007/s00702-006-0543-1

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その他リンク： http://orcid.org/0000-0003-4409-3096

掲載種別：研究論文（学術雑誌）   出版者・発行元：9  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PSYCHOLOGICAL REPORTS  

This study investigated the relationship between subjective and objective quality of life and assessed predictors in people with schizophrenia. The study population consisted of 99 stabilized outpatients with schizophrenia (DSM-IV) who had been regularly receiving outpatient treatment at the Department of Psychiatry, The Tokushima University Hospital. Subjective and objective quality of life were estimated using the Schizophrenia Quality of Life Scale and the Quality of Life Scale, respectively. Psychiatric symptoms were also measured with the Brief Psychiatric Rating Scale and the Calgary Depression Scale for Schizophrenia. Scores on the Schizophrenia Quality of Life Scale Motivation and Energy scales significantly correlated with the Quality of Life Scale total scores -.40 (p &lt;.001), and with the scores on Interpersonal Relations subscale -.42 (p &lt;.001), Instrumental Role subscale -.28 (p=.005), Intrapsychic Foundations subscale -39 (p &lt;.001), and Common Objects and Activities subscale -.25 (P=.014). The Schizophrenia Quality of Life Scale Psychosocial scale significantly correlated with only the Quality of Life Scale total score -.20 (p=.05), and there was no significant correlation between the scores on the Schizophrenia Quality of Life Scale Symptoms and Side-effects scales and the Quality of Life Scale. Stepwise regression analyses showed that the Calgary Depression Scale for Schizophrenia score was the most important predictor of each scale of the Schizophrenia Quality of Life Scale, and the Brief Psychiatric Rating Scale Negative Symptoms score was the most important predictor of the Quality of Life Scale total score and each subscale. These results suggest that subjective and objective quality of life have different predictors and should be considered as separate and complementary outcome variables.

DOI： 10.2466/PR0.99.2.477-487

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JOHN WILEY & SONS LTD  

Replacement of antipsychotic drugs with quetiapine (QTP) was tried in a naturalistic setting in chronic schizophrenic patients who still showed moderate psychiatric symptoms and either showed extrapyramidal symptoms (EPS) or took antiparkinson drugs for the EPS. QTP was added on and gradually increased while the previous drugs were tapered and discontinued whenever possible. Clinical symptoms, objective and subjective QOL, and EPS were measured before and 6 months after QTP addition, using Brief Psychiatric Rating Scale (BPRS), Quality of Life Scale (QLS), Schizophrenia Quality of Life Scale (SQLS) and Drug-Induced Extrapyramidal Symptom Scale (DIEPSS), respectively. Twenty-one patients completed the trial and received the assessment. It was found that replacement with QTP-improved clinical symptoms, objective and subjective QOL and EPS. This improvement was equally observed in not only patients who switched to QTP monotherapy (n = 11) but also patients who took QTP together with reduced small doses (4.4 +/- 4.3 mg/day) of previous drugs (n = 11). The results suggest that replacement with QTP improves symptoms as well as objective and subjective QOL in a subgroup of schizophrenia. Copyright (c) 2006 John Wiley & Sons, Ltd.

DOI： 10.1002/hup.801

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その他リンク： http://orcid.org/0000-0003-4409-3096

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PSYCHOLOGICAL REPORTS  

This study investigated the relationship between subjective and objective quality of life and assessed predictors in people with schizophrenia. The study population consisted of 99 stabilized outpatients with schizophrenia (DSM-IV) who had been regularly receiving outpatient treatment at the Department of Psychiatry, The Tokushima University Hospital. Subjective and objective quality of life were estimated using the Schizophrenia Quality of Life Scale and the Quality of Life Scale, respectively. Psychiatric symptoms were also measured with the Brief Psychiatric Rating Scale and the Calgary Depression Scale for Schizophrenia. Scores on the Schizophrenia Quality of Life Scale Motivation and Energy scales significantly correlated with the Quality of Life Scale total scores -.40 (p &lt;.001), and with the scores on Interpersonal Relations subscale -.42 (p &lt;.001), Instrumental Role subscale -.28 (p=.005), Intrapsychic Foundations subscale -39 (p &lt;.001), and Common Objects and Activities subscale -.25 (P=.014). The Schizophrenia Quality of Life Scale Psychosocial scale significantly correlated with only the Quality of Life Scale total score -.20 (p=.05), and there was no significant correlation between the scores on the Schizophrenia Quality of Life Scale Symptoms and Side-effects scales and the Quality of Life Scale. Stepwise regression analyses showed that the Calgary Depression Scale for Schizophrenia score was the most important predictor of each scale of the Schizophrenia Quality of Life Scale, and the Brief Psychiatric Rating Scale Negative Symptoms score was the most important predictor of the Quality of Life Scale total score and each subscale. These results suggest that subjective and objective quality of life have different predictors and should be considered as separate and complementary outcome variables.

DOI： 10.2466/PR0.99.2.477-487

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その他リンク： http://orcid.org/0000-0003-4409-3096

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER IRELAND LTD  

Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor that promotes several functions of neurons and modulates neurotransmissions. It has been reported that there are alterations of BDNF levels in schizophrenic brains and that BDNF gene expressional changes would be responsible for the etiology of schizophrenia. Recent studies have shown that a variation of BDNF gene (Va166Met polymorphism) affects the function of neurons, and is associated with several neurological and psychiatrical disorders. We investigated the relationship between BDNF Va166Met polymorphism and the onset age as well as levels of clinical symptoms in 159 of chronic schizophrenia in-patients diagnosed by DSM-IV. The mean onset ages were 27.5 +/- 9.5 for BDNF Val/Val, 25.5 +/- 7.4 for BDNF Val/Met and 22.9 +/- 6.0 for BDNF Met/Met and this polymorphism was significantly associated with age at onset (P=0.023). The mean Brief Psychiatric Rating Scale scores (BPRS) were significantly different among those three groups (P=0.003). No significant differences were demonstrated comparing the BDNF genotype distributions of positive and negative family history (P=0.21). Our investigation indicates that the BDNF gene Va166Met polymorphism is related to the onset age of schizophrenia and the levels of clinical symptoms that remain after long-term antipsychotic treatment. (c) 2006 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.neulet.2006.02.054

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その他リンク： http://orcid.org/0000-0003-4409-3096

掲載種別：研究論文（学術雑誌）  

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記述言語：英語   出版者・発行元：ELSEVIER SCIENCE INC  

DOI： 10.1016/j.genhosppsych.2005.05.008

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その他リンク： http://orcid.org/0000-0003-4409-3096

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：OXFORD UNIV PRESS  

Several cases of alcohol-induced bladder dysfunction have been reported previously, but the mechanism of its development is varied and unclear. We report a case of symptomatic abdominal distension due to urinary retention after alcohol withdrawal. The timing of the onset suggests that it was induced by alcohol withdrawal.

DOI： 10.1093/alcalc/agh118

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その他リンク： http://orcid.org/0000-0003-4409-3096

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：OXFORD UNIV PRESS  

We present a case of Korsakoff's syndrome that was successfully treated with high doses of donepezil, an inhibitor of acetylcholine esterase, known to retard the progress of symptoms in Alzheimer's disease. The patient was a 46-year-old married Japanese woman who began to drink alcohol after she married. After several years of drinking she developed typical symptoms of the Korsakoff syndrome. Donepezil was started after treatment with thiamine or thiamine plus fluvoxamine had failed. Her amnestic symptoms as well as her quality of Life improved markedly during donepezil treatment. Inhibition of acetylcholine esterase may be an effective treatment for Korsakoff's syndrome.

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その他リンク： http://orcid.org/0000-0003-4409-3096

J-GLOBAL

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記述言語：日本語   出版者・発行元：(有)科学評論社  

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記述言語：日本語   出版者・発行元：大道学館出版部  

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記述言語：日本語   出版者・発行元：日本うつ病学会・日本認知療法・認知行動療法学会  

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記述言語：日本語   出版者・発行元：日本うつ病学会・日本認知療法・認知行動療法学会  

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記述言語：日本語   出版者・発行元：(株)星和書店  

大うつ病性障害(うつ病)は治療の終結が可能な疾患であるが再発が多い疾患でもある。うつ病治療は抑うつエピソードから寛解に至る急性期治療、寛解から半年ほど治療を継続して回復に至る持続療法、回復してからも再発予防のために治療を継続する維持療法、治療を終了する終了期の段階を経る。それぞれの段階で患者の回復とQOL改善を図るための工夫があり、世界各国のガイドラインもその重要性を指摘している。つまりうつ病においては維持治療の続け方とやめ方の両面が重要である。維持療法の有無や期間について絶対の正解はないが、再発リスクと維持療法のメリット・デメリットについて患者や家族と十分に相談して納得して治療を受けてもらうこと(Shared Decision Making)が重要と考えられる。(著者抄録)

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記述言語：日本語   出版者・発行元：日本うつ病学会・日本認知療法・認知行動療法学会  

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記述言語：日本語   出版者・発行元：日本うつ病学会・日本認知療法・認知行動療法学会  

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記述言語：日本語   出版者・発行元：(株)星和書店  

大うつ病性障害(うつ病)は治療の終結が可能な疾患であるが再発が多い疾患でもある。うつ病治療は抑うつエピソードから寛解に至る急性期治療、寛解から半年ほど治療を継続して回復に至る持続療法、回復してからも再発予防のために治療を継続する維持療法、治療を終了する終了期の段階を経る。それぞれの段階で患者の回復とQOL改善を図るための工夫があり、世界各国のガイドラインもその重要性を指摘している。つまりうつ病においては維持治療の続け方とやめ方の両面が重要である。維持療法の有無や期間について絶対の正解はないが、再発リスクと維持療法のメリット・デメリットについて患者や家族と十分に相談して納得して治療を受けてもらうこと(Shared Decision Making)が重要と考えられる。(著者抄録)

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記述言語：日本語   出版者・発行元：日本うつ病学会・日本認知療法・認知行動療法学会  

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記述言語：日本語   出版者・発行元：(株)星和書店  

躁病/軽躁病エピソードの正確な診断にはまず診断基準を正確に把握する必要がある。診断特異度を高める目的でDSM-IVからDSM-5への更新においていくつかの変更があった。気分の異常だけでなく活動や活力の異常を伴うことや「ほぼ毎日、1日の大半において持続する」ことが追加された点は併存疾患や鑑別疾患を考えるうえで重要である。「混合性の特徴を伴う」という特定用語の使用により、双極性障害やうつ病に伴う軽度の躁症状が診断しやすくなった。過去の躁病/軽躁病エピソードの聴取、通院中の患者の躁病状の早期発見、重症の躁病エピソードの診断、抗うつ薬による躁転でも正確な診断が求められる。衝動性や易怒性、精神運動興奮などが共通点として挙げられる統合失調症/統合失調感情障害、不安症、心的外傷後ストレス障害、物質関連障害、境界性パーソナリティ障害、注意欠如・多動症を鑑別疾患として考察した。(著者抄録)

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記述言語：日本語   出版者・発行元：(株)メディカルレビュー社  

近赤外線スペクトロスコピーはすでに臨床応用が進んでおり、うつ病の診断バイオマーカーとして一歩リードしている。血液を用いた診断バイオマーカーは複数のマーカーを組み合わせて、感度と特異度を上げる方策が試みられている。近年は、血液のDNAメチル化率やmiRNA量などエピジェネティックスにかかわるバイオマーカーに注目が集まっている。(著者抄録)

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記述言語：日本語   出版者・発行元：(株)先端医学社  

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記述言語：日本語   出版者・発行元：(公社)日本精神神経学会  

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記述言語：日本語   出版者・発行元：(株)医学書院  

＜文献概要＞ガイドラインのポイント ・「疾病負荷とケアの原則」,「精神療法」,「薬物療法」,「神経刺激療法」,「補完代替医療」,「特別な患者(児童思春期,女性,高齢者)の治療」の6つのパートからなる。・多くのガイドラインが基準としているAppraisal of Guidelines for Research & Evaluation II(AGREEII)やGrading of Recommendations, Assessment, Development and Evaluations(GRADE)systemに従うのみならず,エキスパートオピニオンを組み入れた独自の評価で推奨を決定している。・エビデンスレベルは1から4に分類される。治療選択の順位はエキスパートオピニオンも臨床的有用性を認めるという前提において,第一選択治療はエビデンスレベルが1または2以上,第二選択治療はレベル3以上,第三選択治療はレベル4以上のエビデンスが存在するというルールがある。・想定している利用者は一般の精神科医や精神医療の専門家である。

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記述言語：日本語   出版者・発行元：(株)先端医学社  

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記述言語：日本語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：日本スポーツ精神医学会  

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記述言語：日本語   出版者・発行元：(株)ワールドプランニング  

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記述言語：日本語   出版者・発行元：(株)ワールドプランニング  

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記述言語：日本語   出版者・発行元：(公社)日本精神神経学会  

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記述言語：日本語   出版者・発行元：(公社)日本精神神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本老年医学会  

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記述言語：日本語   出版者・発行元：(株)ワールドプランニング  

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J-GLOBAL

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記述言語：日本語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：(一社)日本内科学会  

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記述言語：日本語   出版者・発行元：(公社)日本精神神経学会  

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記述言語：日本語   出版者・発行元：(株)中外医学社  

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記述言語：日本語   出版者・発行元：(公社)日本精神神経学会  

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記述言語：日本語   出版者・発行元：(株)中外医学社  

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記述言語：日本語   出版者・発行元：(株)星和書店  

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記述言語：日本語   出版者・発行元：(公社)日本精神神経学会  

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記述言語：日本語   出版者・発行元：(公社)日本精神神経学会  

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記述言語：日本語   出版者・発行元：(公社)日本精神神経学会  

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記述言語：日本語   出版者・発行元：(株)医学書院  

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記述言語：日本語   出版者・発行元：(株)星和書店  

本稿では統合失調症薬物治療ガイドラインの第2章「再発・再燃時」について症例を通して実践的使用法を紹介した。再燃再発時の対応は最も頻回に遭遇する重要な局面であり、急性期症状を改善して維持期に移行する、あるいは治療抵抗性統合失調症と診断してclozapineを導入するといった次のステップに滞りなく進めるには、以下の事項の確認が必須である。CQ2-1ではアドヒアランスを確認しながら抗精神病薬を単剤で十分量、十分期間観察するための工夫が示されている。CQ2-2では各抗精神病薬の投与量と注意すべき副作用、CQ2-3とCQ2-4では抗精神病薬の併用やそれ以外の向精神薬の併用の是非についてエビデンスを提示している。実践的使用法として医師だけでなく看護師や薬剤師による疑義照会や服薬指導、クリニカルパスの作成、患者・家族と主治医が治療の根拠となる情報を共有し、話し合って方針を決める(Shared Decision Making)際の一助として利用してもらえれば、ガイドラインに基づく治療が広く普及していく可能性がある。(著者抄録)

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記述言語：日本語   出版者・発行元：愛媛医学会  

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記述言語：日本語   出版者・発行元：(株)メディカルレビュー社  

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記述言語：日本語   出版者・発行元：(一社)日本サイコオンコロジー学会・日本臨床死生学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本認知症学会  

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記述言語：日本語   出版者・発行元：(一社)日本認知症学会  

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記述言語：日本語   出版者・発行元：(有)科学評論社  

徳島大学病院での、がん患者を対象とした緩和ケアチーム(PCT)心理士による心理相談と精神科医による診療の活動内容を整理し、がん患者の心理面への支援における心理士と精神科医の分担と連携のあり方についての一例として提示した。PCT心理士が介入した患者は、294名(男性106名、女性188名)で、がん患者が254名、非がん患者が40名であった。精神科医診察があった患者は90名であった。このうち、がん患者は70名、非がん患者が20名であった。心理士介入の前に精神科医診察があった患者は54名、心理士介入の後に精神科医診察があった患者は36名であった。がん患者254名における心理士への依頼理由は、心理的問題によるものが142名と過半数を占めた。精神科に紹介となったがん患者は、男性患者の方が多く、せん妄の有病率の高さを反映していると考えられた。精神科に紹介となった患者のうち、がん患者の割合は3割であった。

J-GLOBAL

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記述言語：日本語   出版者・発行元：日本生物学的精神医学会・日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：日本生物学的精神医学会・日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：日本生物学的精神医学会・日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：日本生物学的精神医学会・日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：日本生物学的精神医学会・日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：日本生物学的精神医学会・日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：日本生物学的精神医学会・日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：日本うつ病学会・日本認知療法・認知行動療法学会  

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記述言語：日本語   出版者・発行元：(公社)日本精神神経学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(公社)日本精神神経学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(公社)日本精神神経学会  

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記述言語：日本語   出版者・発行元：(公社)日本精神神経学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(株)星和書店  

APA、WFSBP、NICE、CANMAT、日本うつ病学会のうつ病治療ガイドラインの維持療法について比較した。維持期の薬物療法については急性期に効果のあった薬剤をそのままの量で4〜9ヵ月継続することを全てのガイドラインが推奨している。認知療法や認知行動療法が再燃再発の予防に有効である。再燃再発のリスクとして頻回のエピソードや残遺症状が共通して挙げられている。再燃再発のリスクが高い患者では2年以上の維持療法を行うことも各ガイドラインが推奨している。終了期には中断症候群に注意して慎重に抗うつ薬を漸減中止する。日本うつ病学会のガイドラインは日本の現状に即した臨床的な記載が多く、うつ病治療に関わる多くの医師にとって役立つ内容と思われた。多くの精神科医がこのガイドラインを利用することでうつ病の適正な治療が均てん化されることを期待したい。(著者抄録)

CiNii Books

J-GLOBAL

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記述言語：日本語   出版者・発行元：多文化間精神医学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(株)星和書店  

認知症には様々な精神症状がみられ、患者のADLの低下や介護者の負担の増大を引き起こす。中でも抑うつ状態は多くの疾患で高率にみられる。認知症に併存する抑うつ状態は治療が困難なことが多く、確立された治療法はない。近年、抗認知症薬として、コリンエステラーゼ阻害薬(donepezil、galantamine、rivastigmine)とNMDA受容体拮抗薬(memantine)の合計4剤が使用できるようになり、認知機能障害に対する効果のみならず、抑うつ状態を含めた精神症状にも効果があると報告されている。本稿では認知症に併存する抑うつ状態への抗認知症薬の効果を中心に報告する。(著者抄録)

CiNii Books

J-GLOBAL

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記述言語：日本語  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(株)医学書院  

＜ポイント＞内科受診の患者が向精神薬を服用している場合は,患者の気持ちに配慮しながら理由を尋ねる.各疾患のガイドラインを参考に,向精神薬の投与量や種類が適切かどうか判断する.複数の抗精神病薬や抗うつ薬が処方されている場合や,ベンゾジアゼピン系薬物が長期間処方されている場合は不適切な処方である可能性が高い.不適切な処方である可能性があれば,そのことを患者・家族および処方医に伝えて適正化を促す.(著者抄録)

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記述言語：日本語   出版者・発行元：(一社)日本認知・行動療法学会  

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記述言語：日本語  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(株)メディカルレビュー社  

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記述言語：英語   出版者・発行元：(一社)日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経精神薬理学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：OXFORD UNIV PRESS  

Web of Science

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記述言語：日本語   出版者・発行元：(公社)日本精神神経学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：OXFORD UNIV PRESS  

Web of Science

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記述言語：日本語   出版者・発行元：(公社)日本精神神経学会  

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記述言語：日本語   出版者・発行元：日本生物学的精神医学会  

うつ病は社会生活に甚大な障害を及ぼす common disease であるが，臨床症状にもとづく診断の一致率は必ずしも高くない。早期発見と治療導入を促進する診断マーカーの確立は，急務の課題である。これまでに研究レベルで血液を用いたうつ病の生物学的指標の探索は数多く行われてきたが，客観的なうつ病の血液診断マーカーはいまだ確立されていない。我々は，DNA メチル化修飾ならびに遺伝子発現に注目したうつ病の診断マーカーの探索を行い，いずれにおいても，うつ病患者群と健常対照者群の弁別において良好な結果を得たため，本稿で紹介する。

DOI： 10.11249/jsbpjjpp.27.1_49

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J-GLOBAL

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記述言語：日本語   出版者・発行元：(公財)先進医薬研究振興財団  

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記述言語：日本語   出版者・発行元：日本生物学的精神医学会  

うつ病は社会生活に甚大な障害を及ぼすcommon diseaseであるが、臨床症状にもとづく診断の一致率は必ずしも高くない。早期発見と治療導入を促進する診断マーカーの確立は、急務の課題である。これまでに研究レベルで血液を用いたうつ病の生物学的指標の探索は数多く行われてきたが、客観的なうつ病の血液診断マーカーはいまだ確立されていない。我々は、DNAメチル化修飾ならびに遺伝子発現に注目したうつ病の診断マーカーの探索を行い、いずれにおいても、うつ病患者群と健常対照者群の弁別において良好な結果を得たため、本稿で紹介する。(著者抄録)

DOI： 10.11249/jsbpjjpp.27.1_49

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その他リンク： http://search.jamas.or.jp/link/ui/2016228482

記述言語：日本語   出版者・発行元：(一社)日本心身医学会  

DOI： 10.15064/jjpm.55.10_1164_2

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記述言語：日本語   出版者・発行元：日本生物学的精神医学会・日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：日本生物学的精神医学会・日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：日本生物学的精神医学会・日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：日本うつ病学会・日本認知療法学会  

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記述言語：日本語   出版者・発行元：(株)先端医学社  

CiNii Books

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その他リンク： http://search.jamas.or.jp/link/ui/2015291398

記述言語：日本語   出版者・発行元：(公社)日本精神神経学会  

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記述言語：日本語   出版者・発行元：(有)科学評論社  

CiNii Books

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その他リンク： http://search.jamas.or.jp/link/ui/2015072484

記述言語：日本語   出版者・発行元：(株)星和書店  

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記述言語：日本語   出版者・発行元：徳島医学会  

J-GLOBAL

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記述言語：日本語  

東京農工大学及び徳島大学精神医学の共同により、大規模臨床データによる精神神経系疾患の診断系の開発を行なうためAWS(Amazon Web Services)のクラウド環境にHadoop、MapReduce、NoSQL、Rなどを組み合わせたビッグデータ解析環境を構築し、大規模データ解析を開始した。今回、PCRアレイ、マイクロアレイなどの多次元データを対象にモンテカルロシミュレーションを用いた最適化によるデータ解析を実施し、多変量の遺伝子及び遺伝子修飾マーカーの組合せによる精神神経系疾患診断系の最適化を試み、そのパフォーマンスを検証したので報告する。

CiNii Books

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記述言語：日本語   出版者・発行元：(公財)先進医薬研究振興財団  

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J-GLOBAL

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記述言語：日本語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：日本医師会  

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記述言語：日本語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：(株)医学書院  

抄録今回我々は,異なる機序の抗うつ薬3剤で抗利尿ホルモン不適合分泌症候群syndrome of inappropriate antidiuretic hormone(SIADH)が生じた1例を経験したので報告する。症例は78歳,女性。反復性うつ病性障害,現在中等症エピソードの診断でX年6月に入院となった。入院中,Na濃度がmirtazapine 7.5mg/日内服下で128mEq/l,escitalopram 15mg/日内服下で128mEq/l,duloxetine 40mg/日内服下で119mEq/lと低Na血症を来しSIADHと診断された。抗うつ薬投与を中止するとNa 135mEq/l前後で経過した。異なる機序の抗うつ薬3剤でSIADHを来した症例は,海外も含めてこれまでに報告がない。高齢者に抗うつ薬を投与する際には作用機序に関わらず低Na血症に注意しながら投与する必要があると考えられた。(著者抄録)

DOI： 10.11477/mf.1405102531

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その他リンク： http://search.jamas.or.jp/link/ui/2013323481

記述言語：日本語   出版者・発行元：(株)星和書店  

本稿では双極性うつ病に対する日本うつ病学会の治療ガイドラインとCanadian Network for Mood and Anxiety Treatments(CANMAT)のガイドライン2013年版を比較しながら、それぞれのガイドラインの特徴と課題について考察した。双極I型とII型の違い、抗うつ薬使用の是非、不安障害や物質使用障害の合併の問題、副作用リスクのエビデンス、新しく期待される治療法などは、新しいエビデンスが集積し、各ガイドラインで議論が深まることが期待される。(著者抄録)

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記述言語：日本語   出版者・発行元：(公社)日本精神神経学会  

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記述言語：日本語   出版者・発行元：(株)星和書店  

精神疾患の転帰評価に役立つ生物学的指標は、方法論の進歩や測定技術の革新に伴って様々な指標が取り上げられている。これらの試みは病態解明の研究と表裏一体に進んでいる。比較的病態が明らかになっているアルツハイマー型認知症は、統合失調症やうつ病と比較するとこの分野の研究が先行している。FDG-PETやMRIを用いた転帰評価はアルツハイマー型認知症では有用である可能性が示されているが、統合失調症やうつ病ではさらなる検討が必要である。PETやMRIなどの画像研究は詳細なデータが得られる反面、撮像の負担が重く、生物学的指標として汎用するのは困難である。血液を使った指標は特にうつ病で盛んに行われているが、一つの指標で診断や転帰評価に十分な感度と特異度を示すものは見つかっていない。近い将来に最も有望なのは、先端的な測定技術を用いて複数の因子を測定し、それらを組み合わせて感度と特異度を上げる方策であると思われる。(著者抄録)

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記述言語：日本語   出版者・発行元：(公財)先進医薬研究振興財団  

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記述言語：日本語   出版者・発行元：(有)科学評論社  

CiNii Books

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その他リンク： http://search.jamas.or.jp/link/ui/2013121392

記述言語：日本語   出版者・発行元：(株)星和書店  

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記述言語：日本語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：(株)星和書店  

GSK-3やIMPaseの阻害作用など、近年明らかになったlithiumの作用機序についてまとめた。最終的にlithiumは成長因子の増加、autophagyの活性化、神経新生の増加、興奮毒性やアポトーシスの減少など、神経保護的な働きを強化する。それぞれの機序はお互いに関連しており、どの機序が最も効果に関連しているかを特定するのは難しい状況であるが、lithiumの作用機序を突き詰めることは双極性障害の生物学に新たな発見をもたらす可能性がある。Lithiumの作用機序に関する臨床研究は始まったばかりであるが、pharmacogenomicsやneuroimagingの研究法は近年著しく進歩しており、さらなる研究成果が期待される。Lithiumの神経保護作用は、双極性障害以外にも脳損傷や脳虚血、アルツハイマー型認知症、ハンチントン舞踏病、筋萎縮性側索硬化症など様々な精神神経疾患に有効であることが議論されており、今後の臨床研究も期待される。(著者抄録)

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記述言語：日本語   出版者・発行元：徳島医学会  

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記述言語：日本語   出版者・発行元：(公社)日本精神神経学会  

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記述言語：日本語   出版者・発行元：(公社)日本精神神経学会  

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記述言語：日本語   出版者・発行元：(有)科学評論社  

青年期の脳腫瘍患者について、家族の予期悲嘆から死別後のグリーフワークまで、子どもを亡くす家族に対する心理的支援を行った事例について考察した。相談者は40代の母であった。週1〜2回程度、状況に応じて面接する形となった。支持的精神療法を基本にした面接が介護者の精神的苦痛緩和や意思決定支援に貢献したと考えられ、家族のみを対象とした心理的支援が家族のQOLを改善し、間接的に患者支援となることが示された。対象喪失をテーマに予期悲嘆への対応からグリーフケアまで継続的に心理面接を行ったことで、母親の悲嘆反応が正常範囲で行われた。心理的支援を受けながら医療スタッフと情報を共有して意思決定をするといった、積極的に病気と向かい合った家族は、医療チーム全体に大きな信頼を抱くようになった。本事例では、初期に著しい予期悲嘆の反応が見られたが、医療者の対応や心理的支援により正常範囲内の悲嘆反応で経過した。

CiNii Books

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その他リンク： http://search.jamas.or.jp/link/ui/2012249228

記述言語：日本語   出版者・発行元：(公財)先進医薬研究振興財団  

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記述言語：日本語   出版者・発行元：日本定位・機能神経外科学会  

フィリピンのマニラおよびパナイ島にてX連鎖ジストニア-パーキンソニズム(XDP)患者の臨床症状に関する調査を行った。XDP患者29例を臨床医(KR)が診察し、ビデオテープに収録した。このうち、家族歴が陰性の1例、および十分な診察状況が収録されなかった3例を除外し、残り25例を解析の対象とした。発症早期と考えられるA群、発症中期と考えられるB群、発症後期と考えられるC群の3グループに分類した。ジストニアの運動スコアはA群でB、C群に比し有意に強かった。A群では他群に比し、頸部・体幹・四肢のジストニアが有意に重度であった。また、UPDRS part IIIはC群でA、B群に比し、B群でA群に比し強かった。ADLスコアはA群でB群に比し悪かった。ADLスコアはA群ではジストニアと、B群ではジストニアおよびパーキンソニズムと、C群ではパーキンソニズムと関連した。

J-GLOBAL

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記述言語：英語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：英語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：英語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：(株)星和書店  

統合失調症の4つの主要ガイドラインAmerican Psychiatric Association(APA、2004)、National Institute for Clinical Excellence(NICE、2009)、World Federation of Societies of Biological Psychiatry(WFSBP、2005、2006)、Expert Consensus Guideline(ECG、2003)について、急性期、回復期(安定期)、治療抵抗性(clozapineの適応)、電気けいれん療法(ECT)の扱いに焦点を絞って概説した。作成意図や作成過程および想定利用者の違いが、それぞれのガイドラインの特徴に反映されている。臨床的な決定を補佐するための1つの手引きを意図していることをわきまえて利用すると、有用な治療学の参考書となる。(著者抄録)

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記述言語：日本語   出版者・発行元：(公社)日本精神神経学会  

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記述言語：日本語   出版者・発行元：(公社)日本精神神経学会  

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記述言語：日本語   出版者・発行元：(有)科学評論社  

CiNii Books

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その他リンク： http://search.jamas.or.jp/link/ui/2011279303

記述言語：日本語   出版者・発行元：(公財)先進医薬研究振興財団  

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記述言語：日本語  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(株)アークメディア  

妊娠20週前後の妊婦113名を対象に、個人の背景や性格傾向、被養育体験・ストレス時の対処行動について調査し、周産期の抑うつの影響を与える心理特性について検討した。その結果、出産後3〜4ヵ月の間に全体の23.0%が抑うつ傾向を呈し、その半数以上は妊娠期も抑うつ傾向にあったことが示された。今回の研究では、この時期に測定しても個人内では差は少ないと思われる性格・被養育体験・ストレス対処行動と、周産期の抑うつとの関連をみた結果、産後に初めて抑うつ傾向を認めた群よりも、妊娠期から認めた群と周産期非抑うつ群との間に、多くの項目でスコアの隔たりのある傾向が認められた。

CiNii Books

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その他リンク： http://search.jamas.or.jp/link/ui/2011058939

記述言語：英語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：徳島医学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：CAMBRIDGE UNIV PRESS  

Web of Science

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：CAMBRIDGE UNIV PRESS  

Web of Science

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：CAMBRIDGE UNIV PRESS