Language：English   Publishing type：Research paper (scientific journal)  

Antipsychotic treatment is vital for patients with schizophrenia even in the perinatal period, but the impact at the molecular biological level on offspring is unclear. The aim of the present study was to investigate the effects of intraperitoneal haloperidol injection to pregnant mice on glutamate and GABA receptors in the brain of offspring mice. Eight-week-old pregnant mice were treated with either intraperitoneal haloperidol or normal saline injection, and their offspring were defined as F1 mice. In addition, eight-week-old male mice were used as acute mice that were intraperitoneally injected with haloperidol or normal saline for 20 days. mRNA expression levels were measured by RT-qPCR. Western blotting was performed of the frontal lobes of F1 mice. In the hippocampi of F1 mice, Grik3 (p = 0.023) and Gabra3 (p = 0.004) mRNA expression levels were significantly higher in the haloperidol group than in the control group, whereas Gria2 (p < 0.001) and Grin2a (p < 0.001) mRNA expression levels were significantly lower in the haloperidol group than in the control group. Gria2 (p = 0.015), and Grik3 (p = 0.037), and Grin2a (p = 0.012) mRNA expression levels were significantly lower in the haloperidol group than in the control group in the frontal lobes of F1 mice. In the hippocampi of acute mice, Grik3 (p = 0.049) and Gabra3 (p = 0.007) mRNA expression levels were significantly decreased in the haloperidol group. Fetal exposure to haloperidol can affect glutamate and GABA receptors through mRNA expression changes in the brain of offspring.

DOI： 10.1016/j.ibneur.2023.09.012

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

BACKGROUND: The number of patients with cognitive disorders is rapidly increasing in the world, becoming not only a medical problem, but also a social problem. There have been many reports that various factors are associated with cognitive dysfunction, but the factors have not yet been fully identified. This was a community-based complete enumeration study which aimed to identify risk and protective factors for dementia. METHODS: The first phase included all residents aged 65 years or older in a town in Japan. They completed many examinations, such as living conditions questionnaires, physical examination, Mini-Mental State Examination, and brain magnetic resonance imaging. The participants with suspected cognitive impairment underwent additional examinations for detailed evaluation in the second phase. Statistical analysis was performed to identify risk and protective factors for dementia after all participants were diagnosed. RESULTS: There were 927 participants in the baseline evaluation; 611 (65.9%) were healthy, 165 (17.8%) had mild cognitive impairment (MCI), and 151 (16.3%) had dementia. The age-standardised prevalence of dementia was 9.5%. Statistical analyses for amnestic MCI and Alzheimer's disease showed that risk factors for cognitive decline were diabetes mellitus, low activities of daily living, and living alone, and that protective factors were history of exercise and drinking habit. CONCLUSION: The present findings suggest that several lifestyle-related diseases and factors are associated with cognitive decline. These results support similar findings from previous studies and will be helpful for preventing dementia in the future.

DOI： 10.1111/psyg.13012

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Language：Japanese   Publisher：(公社)日本精神神経学会  

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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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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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Language：Japanese   Publisher：(公社)日本精神神経学会  

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.heliyon.2023.e13059

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AIMS: Body dissatisfaction (BD) is a serious problem related to the incidence of eating disorders. Social media (SM) use is known to be associated with BD. With a view to preventing the incidence of eating disorders, this study aimed to investigate the association between SM and BD, particularly, the role of SM in the encouragement of thinness and its relationship with adolescent girls' BD. METHODS: Junior high school girls aged 12-15 in Japan completed the Body Shape Questionnaire (BSQ), Eating Attitudes Test-26, Bulimic Investigatory Test Edinburgh, Depression Self-Rating Scale for Children, and SM usage. Participants were classified into two groups based on their BSQ cut-off score. RESULTS: Overall, 161 students were recruited (44 participants with BD; 117 without BD). The BD group used SM more than the non-BD group (χ2 (1) = 4.61, p = .032). The frequency of following SM accounts related to thinness was significantly higher in the BD group than in the non-BD group (χ2 (1) = 7.76, p = .005). The association between BD and following SM accounts focused on thinness was the most important (adjusted OR = 3.82; 95 % CI: 1.05-13.89). CONCLUSIONS: The risks of SM use increasing BD in adolescent girls should be considered to prevent mental disorders, including eating disorders.

DOI： 10.1016/j.eatbeh.2022.101685

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In recent years, concerns about internet addiction (IA) among children have been increasing. This study focused on the awareness of IA in elementary school teachers. A web-based anonymous survey was conducted in November 2021. The participants completed an original questionnaire about their awareness of IA. The participants were divided into three groups based on their positions in the classroom: class teachers, support teachers, and administrative teachers. Out of 283 participants, over 70% had not approached students with IA and had little practical knowledge about the disorder. Support and administrative teachers had more opportunities to interact with students with IA than class teachers (p < 0.001 in both cases). Support teachers had more opportunities to ask their colleagues about IA than class teachers (p < 0.01); similarly, administrative teachers also had more opportunities to discuss IA with colleagues than class teachers (p = 0.04). Preventive interventions are recommended for people who communicate with children with IA. Students with IA might cause anxiety among teachers; therefore, preventive education strategies should be implemented with the cooperation of psychiatrists, psychologists, and public health nurses.

DOI： 10.3389/fpsyt.2023.1187387

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DOI： 10.3390/brainsci13010027

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Publishing type：Research paper (scientific journal)   Publisher：Wiley  

DOI： 10.1002/pcn5.65

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Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/pcn5.65

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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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Publishing type：Research paper (scientific journal)   Publisher：Wiley  

DOI： 10.1002/pcn5.33

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Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/pcn5.33

Language：Japanese   Publisher：(株)星和書店  

感染症による精神疾患においては、感染症が直接引き起こす器質性精神障害と、既知の精神障害が感染症によって影響される場合とがある。前者の代表例として神経梅毒が挙げられる。一方、新型コロナウイルス感染症(COVID-19)では、双方が引き起こされる可能性がある。また、抗菌薬など身体治療による精神症状の発現や向精神薬との薬物相互作用にも気をつけなければならない。この稿では、これら感染症による精神障害の捉え方、そこで注意することに触れた後に、最後に、薬物以外で心に留めなければいけないことについても概説する。(著者抄録)

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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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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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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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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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Esports (electronic sports) programs are a variant of competitive gaming and have expanded worldwide in recent years. The prevalence of problematic gaming and gaming disorders (GD) is predicted to increase in adolescents. Children with autism spectrum disorder (ASD) have a high rate of digital gaming use, and their characteristics, such as social communication deficits and restricted interests, might contribute to problematic gaming. In this study, we aimed to examine whether participation in an Esports program would lead to problematic gaming or GD in children with ASD. The Internet Gaming Disorder Test (IGD-20) scores, Kid-KINDL scores, and gaming time at home were assessed in eight children with ASD before beginning the Esports program and at the three-month follow-up timepoint. The program was held once a week at the welfare service center, where the participants played a set game for 60 min. The results indicated there was no significant worsening in any of the scores after the program. Our program provided the participation time and frequency of Esports, type of game, and motivation of the participants are adequately considered. Even though this pilot study is limited by the small sample size, we concluded that the risk of these activities leading to problematic gaming might be low.

DOI： 10.3390/bs12060172

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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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Language：Japanese   Publisher：(公社)日本精神神経学会  

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Language：Japanese   Publisher：(公社)日本精神神経学会  

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Language：Japanese   Publisher：(公社)日本精神神経学会  

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Language：English   Publishing type：Research paper (scientific journal)  

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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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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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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BACKGROUND: Overadaptation, the behavior of individuals who follow the expectations of others as perfectly as possible, is often observed and related to maladjustment, school refusal, and physical symptoms; however, no method has been proposed yet to assess the overadaptive tendency. This study evaluated the efficacy of the draw-a-man test as a projective measure of overadaptation in community children. METHODS: Eighty children (36 boys, 44 girls) aged 6-8 years were assessed for their ability to draw a man using the Goodenough Draw-A-Man Test (DAM test). Class teachers were asked to assess whether the child was overadapting. The total and subscale DAM scores and pass rates were compared between children with a teacher-assessed tendency for overadaptation and control children, separately for girls and boys. RESULTS: The mean total DAM score was significantly higher for girls versus boys for both the overadapting children and controls. For boys, no significant differences on the total and subscale DAM scores were noted between the overadapting boys and controls. Conversely, for girls, total and three subscale DAM scores (Mouth/Nose/Ears, Hairs, Fingers) were significantly higher in the overadapting girls versus controls. Moreover, for girls, the DAM pass rates on five items (ratio of head; ears present; position and shape of nose; depiction of hair, not to see the scalp; details of fingers) were higher in the overadapting girls versus controls. CONCLUSIONS: The DAM test could extract the overadaptive tendencies of girls aged 6-8 years.

DOI： 10.1111/ped.14919

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Language：Japanese   Publisher：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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Language：Japanese   Publisher：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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Children with autism spectrum disorder (ASD) could experience more stress due to the changes consequent to school closures because of the coronavirus disease 2019 (COVID-19) pandemic. This study investigated differences in behavioral affect between children with ASD and typically developing children (TD). We conducted an online survey with mothers. The data of 84 children with ASD and 361 TD children aged 6 to 18 years were analyzed. Children with ASD were more frustrated due to the changes in their schedule and engaged more in restricted and repetitive behavior. Children with ASD had different types of behavioral affect compared to TD.

DOI： 10.1080/87565641.2021.1939350

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The importance of epigenetic control in the development of the central nervous system has recently been attracting attention. Methylation patterns of lysine 4 and lysine 36 in histone H3 (H3K4 and H3K36) in the central nervous system are highly conserved among species. Numerous complications of body malformations and neuropsychiatric disorders are due to abnormal histone H3 methylation modifiers. In this study, we analyzed a Japanese family with a dominant inheritance of symptoms including Marfan syndrome-like minor physical anomalies (MPAs), intellectual disability, and schizophrenia (SCZ). We performed positional cloning for this family using a single nucleotide polymorphism (SNP) array and whole-exome sequencing, which revealed a missense coding strand mutation (rs1555289644, NM_032590.4: c.2173G>A, p.A725T) in exon 15 on the plant homeodomain of the KDM2B gene as a possible cause of the disease in the family. The exome sequencing revealed that within the coding region, only a point mutation in KDM2B was present in the region with the highest logarithm of odds score of 2.41 resulting from whole genome linkage analysis. Haplotype analysis revealed co-segregation with four affected family members (IV-9, III-4, IV-5, and IV-8). Lymphoblastoid cell lines from the proband with this mutation showed approximately halved KDM2B expression in comparison with healthy controls. KDM2B acts as an H3K4 and H3K36 histone demethylase. Our findings suggest that haploinsufficiency of KDM2B in the process of development, like other H3K4 and H3K36 methylation modifiers, may have caused MPAs, intellectual disability, and SCZ in this Japanese family.

DOI： 10.1038/s10038-020-00889-4

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BACKGROUND: Sleep is essential for mental health at all ages, but few studies have investigated the importance of sleep for mental health in early childhood. Therefore, this study examined the association between mental health and sleep habits/problems in children aged 3-4 years. METHODS: Children aged 3 to 4 years who were living in the community (n = 415; 211/204 boys/girls) were recruited for this study. Their mental health was assessed using the Strengths and Difficulties Questionnaire (SDQ), and their sleep habits/problems were evaluated using the Child and Adolescent Sleep Checklist. RESULTS: Based on the total difficulties score of the SDQ, the children were divided into two groups: a poor mental health group (n = 76) and a control group (n = 339). In terms of sleep habits, which included total sleep time, bedtime, wake time, and nap conditions, there were no differences between the two groups. Regarding sleep-related problems, however, anxiety before going to sleep (p = 0.026), circadian rhythm abnormalities (p = 0.014), and sleepiness during classes outside of naptimes (p = 0.031) were significantly higher in the poor mental health group than in the control group. Multiple regression analysis showed that poor mental health status was significantly associated with sleepiness and snoring (p = 0.017 and p = 0.018, respectively). CONCLUSIONS: The mental health status of 3-4-year-old children was associated with sleep-related problems, namely sleepiness and snoring. Healthcare providers should pay attention to children's irregular sleep-wake patterns; moreover, interventions for appropriate sleep hygiene will reduce the psychological burden on both children and their families.

DOI： 10.1186/s13030-021-00213-2

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The purpose of this study was to elucidate the relationship between the severity of Internet addiction and various media-related applications. The participants were junior high school students between 12 and 15 years old. A total of 529 students (283 males, 246 females) were included. The participants answered Young's Internet Addiction Test (IAT) and a structural questionnaire about their access to electronic devices and applications. An Internet addiction prevalence of 4.3% (95% CI: 2.8-6.5%) was reported in this study, with an additional 26.3% (95% CI: 22.6-30.2%) of participants possibly addicted. The accessibility of gaming devices was significantly higher in male students than in female students. The use of applications for SNSs was significantly higher in female students than in male students. Twitter accessibility was a factor that contributed to Internet addiction in both genders. The prevalence of severe Internet addiction among school students in Japan was 4.3%, and Twitter was the most important factor associated with this addiction. Media literacy must be increased in adolescents and their friends, teachers, and families.

DOI： 10.3390/ijerph18094844

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Language：English   Publishing type：Research paper (scientific journal)  

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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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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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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Publishing type：Research paper (scientific journal)   Publisher：SAGE Publications  

Objective. The perception of emotion and behavior is different between adolescents and their parents. Parent-adolescent agreement on emotional and behavioral problems has not been well researched. The aim of this study was to explore and compare how well the information from themselves matches with the judgments by their parents in terms of emotional and behavioral problems. Methods. The cross-sectional study was conducted using the self-report and parent-report Strengths and Difficulties Questionnaire (SDQ). A total of 1254 Japanese school adolescents aged 12 to 18 and their parents were assessed almost the same time. The results were analyzed using the paired t-test and 2-way analysis of variance for the discrepancies of parent-adolescent agreements in each age and gender groups. Results. Adolescents obtained higher total difficulty and all subscales scores of SDQ than their parents. The effect of grade on the self/parent discrepancy scores were significantly observed on the conduct problems ( P &lt; .001), hyperactivity ( P = .009), and prosocial behavior ( P &lt; .001). The effect of gender was shown significantly on the emotional problems ( P &lt; .001), conduct problems ( P &lt; .001), and peer problems ( P = .002). Conclusion. Adolescents reported more problems than their parents did. For comprehensive evaluation of adolescents’ mental health, it is necessary to draw information from both the adolescents themselves and their parents, and pay attention to the gap between adolescents and their parents’ perception.

DOI： 10.1177/2333794x211001245

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Other Link： http://journals.sagepub.com/doi/full-xml/10.1177/2333794X211001245

Language：English   Publishing type：Research paper (scientific journal)  

School closure due to coronavirus disease 2019 (COVID-19) pushed children across ages and nationalities into a state of mental health crisis. In Japan, children between the ages of 6 and 18 were ordered to stay at home and observe social distancing for several months. This study is aimed at investigating the effects of quarantine due to COVID-19 on children belonging to different developmental stages in life. Data were collected from mothers of typically developing children aged between 6 and 18 years. The differences in psychological and behavioral changes following school closure during the COVID-19 pandemic were explored. A total of 535 children, including 145 students in lower grades of elementary school (6-9 years), 124 students in higher grades of elementary school (9-12 years), 132 students in junior high school (12-15 years), and 134 students in high school (15-18 years), were recruited. Children in lower grades of elementary school (lower grades group) gained significantly lower understanding about COVID-19 and the necessity of COVID-19 restrictions than children in the other groups. Moreover, they had more psychological problems: they easily cried and complained, were unable to keep calm, and were dependent on parents and family members. Changes in sleep patterns were more prevalent in junior and senior high school students. We concluded that mental health care should be provided based on the growth period of each child not only during school closure but also after school reopening.

DOI： 10.1155/2021/5567732

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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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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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Language：English   Publishing type：Research paper (scientific journal)  

Objective. The perception of emotion and behavior is different between adolescents and their parents. Parent-adolescent agreement on emotional and behavioral problems has not been well researched. The aim of this study was to explore and compare how well the information from themselves matches with the judgments by their parents in terms of emotional and behavioral problems. Methods. The cross-sectional study was conducted using the self-report and parent-report Strengths and Difficulties Questionnaire (SDQ). A total of 1254 Japanese school adolescents aged 12 to 18 and their parents were assessed almost the same time. The results were analyzed using the paired t-test and 2-way analysis of variance for the discrepancies of parent-adolescent agreements in each age and gender groups. Results. Adolescents obtained higher total difficulty and all subscales scores of SDQ than their parents. The effect of grade on the self/parent discrepancy scores were significantly observed on the conduct problems (P < .001), hyperactivity (P = .009), and prosocial behavior (P < .001). The effect of gender was shown significantly on the emotional problems (P < .001), conduct problems (P < .001), and peer problems (P = .002). Conclusion. Adolescents reported more problems than their parents did. For comprehensive evaluation of adolescents' mental health, it is necessary to draw information from both the adolescents themselves and their parents, and pay attention to the gap between adolescents and their parents' perception.

DOI： 10.1177/2333794X211001245

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Language：English   Publishing type：Research paper (scientific journal)  

Sleep disturbances are the comorbid conditions most frequently associated with autism spectrum disorder (ASD). Sleep problems might precede and worsen the behavioral outcomes of ASD. This study examined the association between sleep habits/problems and autistic traits in toddlers. Eighteen-month-old toddlers (N= 426; boys/girls, 204/222) were assessed for autistic traits using the Japanese version of the Modified Checklist for Autism in Toddlers and sleep habits/problems using the Child and Adolescent Sleep Checklist during health checkups. There were no significant differences in sleep habits, including total sleep time, wake time, bedtime, and naps, between autistic toddlers (n= 26) and non-autistic toddlers (n= 400). However, toddlers with autistic traits more commonly exhibited bedtime resistance, abnormality in circadian rhythm, and sleepiness outside of naptime than toddlers without autistic traits. Moreover, autistic traits were significantly associated with daytime sleepiness. Autistic traits are associated with sleep problems in toddlers. In particular, daytime sleepiness might be avisible symptom that enables the earlier detection of ASD in children.

DOI： 10.1080/87565641.2020.1865357

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Publishing type：Research paper (scientific journal)   Publisher：Frontiers Media SA  

Internet use in the youth has increased manifold during the coronavirus disease 2019 (COVID-19) pandemic. Individuals with autism spectrum disorder (ASD) generally have a higher risk of problematic internet use. The aim of this study is to investigate the differences in internet and related digital media use between children with ASD and their typically developing counterparts during the COVID-19 pandemic. In this online survey in Japan conducted from April 30 to May 8, 2020, we analyzed digital media time of 84 children with ASD and 361 age- and gender-matched controls before and after school closure. Digital media use duration was significantly longer in the ASD group than in the control group before the pandemic. The increase of media use time was more prominent in the control group than in the ASD group. We observed excessive Internet use among children with ASD and without ASD, especially during the COVID-19 pandemic. It is necessary to establish strategies to prevent excessive internet use in not only children and adolescents with ASD but also without ASD in the post-pandemic world.

DOI： 10.3389/fpubh.2020.609347

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Language：Japanese   Publisher：(株)ワールドプランニング  

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Language：English  

DOI： 10.1111/pcn.13090

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Language：Japanese   Publisher：(公社)日本精神神経学会  

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Language：Japanese   Publisher：(公社)日本精神神経学会  

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Language：Japanese   Publisher：(公社)日本精神神経学会  

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Language：English   Publishing type：Research paper (scientific journal)  

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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BACKGROUND: Internet addiction is a serious problem, and the incidence has increased significantly in recent years. In two cross-sectional studies over a 4-year period, we investigated Internet addiction in adolescents and evaluated the resulting changes in their lives. METHODS: Junior high-school students (aged 12 to 15 years) were assessed in 2014 (survey I) and in 2018 (survey II). They filled out Young's Internet Addiction Test (IAT), the Japanese version of the General Health Questionnaire, and a questionnaire on sleep habits and usage of electric devices. RESULTS: In total, 1,382 students were recruited for the two surveys. The mean IAT score was significantly higher in survey II (36.0 ± 15.2) than in survey I (32.4 ± 13.6) (P < 0.001). The increase in total IAT score indicates that the rate of Internet addiction was significantly higher in 2018 than in 2014. For each subscale of the General Health Questionnaire, social dysfunction scores were significantly lower in survey II than in survey I (P = 0.022). During the weekend, mean total sleep time was 504.8 ± 110.1 min, and the time awake was 08:02 h in survey II; the total sleep time and time awake were significantly longer and later, respectively, in survey II than in survey I (P < 0.001, P = 0.004, respectively). Smartphone use was also significantly higher in survey II than in survey I (P < 0.001). CONCLUSIONS: The prevalence of Internet addiction differed over the 4 years of this study.

DOI： 10.1111/ped.14250

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Language：English   Publisher：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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Language：Japanese   Publisher：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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Language：English   Publishing type：Research paper (scientific journal)  

Children are increasingly exposed to electronic media, which can potentially influence their sleep habits. However, few studies have investigated the effects of children's life patterns on sleep habits and electronic media usage. This study investigated the differences in sleep habits and electronic media usage between 18- and 42-month-old children attending nursery schools, kindergartens, or staying at home, and respectively enrolled 183 (boys, n = 93; girls, n = 90) and 215 (boys, n = 104; girls, n = 111) 18- and 42-month-old children who underwent health check-ups. We found that 18-month-old children attending nursery school had significantly earlier wake times on weekdays and shorter sleep durations on weekends than children who stayed at home despite no differences in electronic media usage. There were no differences in sleep duration among 42-month-old children attending nursery schools, kindergartens, or staying at home; however, kindergarteners demonstrated a higher use of portable and home video games. Different life patterns affect electronic media usage in preschool children, especially those attending kindergarten. Particular attention should be paid to the higher usage of electronic media devices by kindergarteners, although they had the same sleep duration, as did other preschool children.

DOI： 10.3390/ijerph17145189

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Language：Japanese   Publisher：(株)医学書院  

＜文献概要＞愛媛大学医学部附属病院は2015年4月に子どものこころセンターを開設した。本調査では,開設後2年間の初診患者の動向を明らかにすることを目的に,後方視的に調査を行った。初診患者は1〜15歳の292例(男性192例,女性100例)であった。約9割が紹介受診であり,最も多い紹介元は院外の小児科(49.7%)であった。ICD-10に基づいて行った診断では,F8が最も多く(43.6%),F4,F9と続いた。2017年3月現在の転帰は,治療継続中が150例(51.4%)で,その3/4が発達障害圏の患者であった。センター化したことで,初診患者数が増加し,低年齢化した。また,小児科からの紹介が増加し,発達障害圏を中心に患者が集約されていた。しかし,地域と当センターの連携の不十分さなどの課題も明らかとなり,今後のセンターのあり方について模索中である。

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Language：Japanese   Publisher：(株)医学書院  

＜文献概要＞愛媛大学医学部附属病院は2015年4月に子どものこころセンターを開設した。本調査では,開設後2年間の初診患者の動向を明らかにすることを目的に,後方視的に調査を行った。初診患者は1〜15歳の292例(男性192例,女性100例)であった。約9割が紹介受診であり,最も多い紹介元は院外の小児科(49.7%)であった。ICD-10に基づいて行った診断では,F8が最も多く(43.6%),F4,F9と続いた。2017年3月現在の転帰は,治療継続中が150例(51.4%)で,その3/4が発達障害圏の患者であった。センター化したことで,初診患者数が増加し,低年齢化した。また,小児科からの紹介が増加し,発達障害圏を中心に患者が集約されていた。しかし,地域と当センターの連携の不十分さなどの課題も明らかとなり,今後のセンターのあり方について模索中である。

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Language：English   Publishing type：Research paper (scientific journal)  

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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Language：English   Publishing type：Research paper (scientific journal)  

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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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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Language：English   Publisher：The Japanese Society of Clinical Neuropsychopharmacology  

<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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Language：English   Publishing type：Research paper (scientific journal)  

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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Language：English   Publishing type：Research paper (scientific journal)  

Background: Few studies have explored school refusal in children with autism spectrum disorder (ASD), despite being considered a serious problem. One of the leading causes of school refusal is bullying, which is defined by the feelings of students who are bullied or not, and psychological suffering caused by a psychological or physical attack. This study investigated the characteristics of school refusal in children with ASD. Methods: A total of 94 outpatients with school refusal and ASD and 143 outpatients with school refusal without ASD aged 6-18 years were included. Chi squared tests and Mann-Whitney tests were used to compare the characteristics of school refusal in children with and without ASD. Univariate and multivariate logistic regression analyses were performed to analyze the reasons for school refusal in children with ASD by sex. Results: School refusal significantly occurred earlier in children with ASD than in those without. In addition, "bullying" was significantly associated with school refusal in both boys and girls with ASD. Conclusions: These findings suggest that school refusal should be monitored early in children with ASD. The importance of recognizing bullying among children with ASD should be highlighted as an opportunity for early intervention.

DOI： 10.1186/s13034-020-00325-7

PubMed

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Language：English   Publisher：The Japanese Society of Clinical Neuropsychopharmacology  

<p><b>Purpose: </b>Although attention-deficit/hyperactivity disorder (ADHD) has historically been thought to be predominantly a childhood disorder, many cases of ADHD persist into adulthood. Therefore, it is necessary to assess the symptoms and efficacy of medication using objective assessment tools in adults with ADHD. The aim of this study was to assess usefulness of the Clinical Assessment for Attention Test (CAT) comprising Span, Cancellation and Detection Test, Symbol Digit Modalities Test, memory updating test, paced auditory serial addition test, position Stroop test, and continuous performance test (CPT) for adults with ADHD.</p><p><b>Methods: </b>ADHD outpatients without intellectual disorders (IQ ≥ 80) with age range of 20-39 years were recruited (15 males and 10 females; mean age 27.7 ± 5.5). The participants did not receive any psychopharmacological treatment and were assessed with CAT at baseline.</p><p><b>Results: </b>The patients showed significantly decreased attention scores in Cancellation and Detection Test (Visual Cancellation Task and Auditory Detection Task) and CPT, although this decrease was not correlated to age or intelligence quotient. The effect of psychopharmacological treatment was assessed in two participants using CAT.</p><p><b>Discussion: </b>Cancellation and Detection Test and CPT are useful tools to support the diagnosis of adults with ADHD as well as evaluation of the efficacy of psychopharmacological treatment.</p>

DOI： 10.5234/cnpt.11.35

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Language：English   Publishing type：Research paper (scientific journal)  

Internet use in the youth has increased manifold during the coronavirus disease 2019 (COVID-19) pandemic. Individuals with autism spectrum disorder (ASD) generally have a higher risk of problematic internet use. The aim of this study is to investigate the differences in internet and related digital media use between children with ASD and their typically developing counterparts during the COVID-19 pandemic. In this online survey in Japan conducted from April 30 to May 8, 2020, we analyzed digital media time of 84 children with ASD and 361 age- and gender-matched controls before and after school closure. Digital media use duration was significantly longer in the ASD group than in the control group before the pandemic. The increase of media use time was more prominent in the control group than in the ASD group. We observed excessive Internet use among children with ASD and without ASD, especially during the COVID-19 pandemic. It is necessary to establish strategies to prevent excessive internet use in not only children and adolescents with ASD but also without ASD in the post-pandemic world.

DOI： 10.3389/fpubh.2020.609347

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Language：English  

DOI： 10.1111/pcn.12935

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Language：English   Publishing type：Research paper (scientific journal)  

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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Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVE: This study examined the association between sleep habits and problems and Internet addiction in adolescents. METHODS: Junior high school students from a local town in Japan (n=853; male/female, 425/428) were the subjects of this study, and were assessed for severity of Internet addiction and sleep habits and problems using the self-reported version of the Young's Internet Addiction Test (IAT) and Child and Adolescent Sleep Checklist (CASC). RESULTS: The wake time on weekdays was not significantly different among the three groups; addicted, possibly-addicted, and non-addicted. In the addicted group, the total night sleep time was significantly shorter, and the bedtime was significantly delayed on both weekdays and weekends compared with those in the possibly-addicted and non-addicted groups. The wake time of the addicted group was significantly later than that of the other groups. The total scores of sleep problems measured by the CASC were significantly higher in the addicted and possibly-addicted groups than in the non-addicted group. CONCLUSION: Internet addiction is strongly associated with sleep habits and problems in adolescents. These findings suggest that internet addiction should be considered while examining adolescent lifestyle.

DOI： 10.30773/pi.2019.03.21.2

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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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Language：Japanese   Publisher：(公社)日本精神神経学会  

インターネットはいまや日常的に必要不可欠なツールとなっており,接続できるデバイスもパーソナルコンピューターのみならず,スマートフォンやタブレット,テレビや携帯型ゲームなどさまざまである.その一方で,インターネット使用の制御が困難となり,生活上の問題をきたすインターネット依存が社会的問題になっている.2018年6月に世界保健機関(WHO)から公表されたICD-11においては,ゲーム障害が収載された.国際的にもインターネット依存およびゲーム障害に関して報告が蓄積されつつある.本稿では,これまでの報告を踏まえ,精神医療におけるインターネット依存の現状について整理する.(著者抄録)

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J00755&link_issn=&doc_id=20190731180002&doc_link_id=vol%3D121%26year%3D2019%26mag%3D0%26number%3D7%26start%3D540&url=https%3A%2F%2Fjournal.jspn.or.jp%2FDisp%3Fstyle%3Dabst%26vol%3D121%26year%3D2019%26mag%3D0%26number%3D7%26start%3D540&type=%90%B8%90_%90_%8Co%8Aw%8EG%8E%8F&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00022_2.gif

DOI： 10.1097/jcp.0000000000000998

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Other Link： http://orcid.org/0000-0003-4409-3096

Language：English   Publishing type：Research paper (scientific journal)  

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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Other Link： http://orcid.org/0000-0003-4409-3096

Language：Japanese   Publisher：(公社)日本精神科病院協会  

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DOI： 10.1016/j.jpsychires.2018.10.011

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Other Link： http://orcid.org/0000-0003-4409-3096

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is characterized by inattention and hyperactivity/impulsivity, and is often treated pharmacologically. It is necessary to use both subjective and objective assessments to diagnose and determine the efficacy of pharmacological treatment in children with ADHD, but cognitive assessment tools for ADHD are scarce. We examined a computer-administered, brief, and repeatable cognitive assessment tool: CogHealth. The aims of this study were to use the CogHealth battery, an objective assessment tool, to compare cognitive function between children with ADHD or ADHD + autism spectrum disorder (ASD) and healthy children and to assess improvements in cognitive function following pharmacological treatment. METHODS: We measured the cognitive function of nine children with ADHD or ADHD + ASD using CogHealth and compared the results with those of 33 age-matched children from the community. Cognitive function comparisons were made before and after psychostimulant treatment with methylphenidate. RESULTS: We detected significant cognitive abnormalities in the children with ADHD, compared with the control subjects. The children with pre-treatment ADHD had significantly more errors on the detection task (DT), and more anticipatory errors in the one card learning task, compared with control children. The children with ADHD significantly improved their accuracy on the one back test (OBT), and had significantly fewer errors, anticipatory errors, and shorter reaction times after osmotic-release oral system methylphenidate treatment. CONCLUSION: The DT is a useful neurocognitive function assessment for children with ADHD, and the OBT can measure pharmacological treatment effectiveness in children with ADHD.

DOI： 10.1111/ped.13662

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Language：Japanese   Publisher：(株)アークメディア  

新版K式発達検査2001(KSPD)を用いた発達指数(DQ)がWISC-IVを用いたIQの代替となり得るかについて検討した。自閉スペクトラム症(ASD)の対象者は、2016年7月から2017年3月に愛媛大学医学部附属病院子どものこころセンターを受診した5から10歳の患者のうち、DSM-5の診断基準によりASDと診断され、WISC-IVにより測定されたFSIQが70以上の9名(男児8名、女児1名、平均月齢99.7ヵ月)とした(ASD群)。また、通常学級または一般の幼稚園に通う児童6名(男児3名、女児3名、平均月齢86.2ヵ月)を定型発達群とした。ASD群において、WISC-IVの言語理解とKSPD全領域DQおよび言語・社会DQとそれぞれ0.859、0.872の相関が確認されたが、定型発達児においては、同指標の相関係数は0.162であった。KSPDとWISC-IVから算出されるDQ・IQの関連性は認められるが、DQ・IQの代替や縦断的に評価には慎重を期す必要があることが示唆された。

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J01552&link_issn=&doc_id=20180913090012&doc_link_id=%2Fao1clphd%2F2018%2F004708%2F012%2F0929-0935%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fao1clphd%2F2018%2F004708%2F012%2F0929-0935%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：English  

The clinical features in cases that have mutations in the microtubule-associated protein tau gene but lack prominent behavioral changes remain unclear. Here, we describe detailed clinical and pathological features of a case carrying the P301L tau mutation that showed only apathy until the middle stage of the course. The mother of this case was suspected to have mild cognitive decline at age 46. However, before she was fully examined, she had a subarachnoid hemorrhage at age 49 and died at age 53. An autopsy was not done. The proband of this pedigree, a 60-year-old right-handed Japanese man at the time of death, began to make mistakes at work at the age of 51 years. Until age 54, he showed only mild apathy with bradykinesia. Insight was well spared. Parkinsonism and echolalia developed at age 55, and pyramidal signs and oral tendency at age 57. Personality change, disinhibition, stereotypy, or semantic memory impairment was not found throughout the course. The final neurological diagnosis was unspecified dementia. Pathological examination demonstrated numerous round four-repeat tau-positive three-repeat tau-negative or perinuclear ring-like neuronal cytoplasmic inclusions with many ballooned neurons in the frontal and temporal cortices and hippocampus. Genetic analysis using frozen brain tissue demonstrated a P301L tau mutation. Among 31 previously reported cases bearing the P301L tau mutation for which the data regarding initial symptoms are available, one clinical case showed only apathy with depression in the early stage. Given these findings, clinicians should be aware that a clinical course characterized only by apathy for several years, which can be misdiagnosed as a psychiatric disorder, is one of the clinical presentations associated with P301L tau mutation.

DOI： 10.1111/neup.12441

Web of Science

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Language：English   Publishing type：Research paper (scientific journal)  

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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Other Link： http://orcid.org/0000-0003-4409-3096

Language：Japanese   Publisher：(株)医学書院  

＜文献概要＞本研究は愛媛大学病院精神科外来において,成人期発達障害における発達障害の特徴を,診療パスの内容により検討することを目的とした。対象は2013〜16年に当院を初診し,発達障害の精査を希望した18歳以上の患者104名(男性57,女性47)である。診療パスは生育歴の聴取や主訴の問診票と,AQ-J,ASRS,CAARS,BDI-II,SFS,SRSなどの質問紙とWAIS-IIIで構成されている。対象者のうちASD29例,ADHD18例,精神疾患に該当しない18例の3群を比較した。結果,ASD群はADHD群と比較して有意に男性,精神症状の主訴が多く,SFSが低値,WAIS-IIIのVIQが高値であった。ADHD群は不注意の主訴,既婚者の割合,ASRSが有意に高かった。診療パスは精神症状や社会機能の把握に一定の有用性があった。本研究は予備的研究であり,診療パスにはさらなる検討が必要である。

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Language：Japanese   Publisher：(公社)日本精神神経学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley-Blackwell  

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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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Blackwell Publishing  

It is very rare that cases of Pick's disease, a representative three-repeat (3R) tauopathy, also have significant four-repeat (4R) tau accumulation. Here, we report a Pick's disease case that clinically showed behavioral variant frontotemporal dementia without motor disturbance during the course, and pathologically had 3R tau-positive Pick bodies as well as numerous 4R tau-positive neuronal cytoplasmic inclusions (NCIs). Abundant 3R tau-positive 4R tau-negative spherical or horseshoe-shaped Pick bodies were found in the frontotemporal cortex, limbic region, striatum and pontine nucleus. On the other hand, many 4R tau-positive, 3R tau-negative, Gallyas-negative dot-, rod- or intertwined skein-like NCIs were found mainly in the subthalamic nucleus, pontine nucleus, inferior olivary nucleus and cerebellar dentate nucleus. Tufted astrocytes, astrocytic plaques, argyrophilic grains or globular glial inclusions were absent. Double-labeling immunofluorescence demonstrated that 3R tau was hardly accumulated in 4R tau-positive inclusions. On tau immunoblotting, while 60 and 64 kDa bands were demonstrated in the frontal cortex, 60, 64 and 68 kDa bands, as well as the 33 kDa tau fragments that are reported to be characteristic of progressive supranuclear palsy brains, were found in the basal ganglia and cerebellum. No mutation was identified in the tau gene. The present case suggests that, although probably rare, some Pick's disease cases have non-negligible 4R tau pathology in the subcortical nuclei, and that such 4R tau pathology can affect the evaluation of the distribution of AT8-positive tau pathology in Pick's disease cases.

DOI： 10.1111/neup.12394

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：MARY ANN LIEBERT, INC  

Objectives: Suvorexant is the first dual orexin receptor antagonist for treating insomnia. This study aimed to evaluate the tolerability, efficacy, and safety of suvorexant on insomnia in adolescents. Methods: Thirty patients (8 male and 22 female; mean standard deviation age: 15.72.4 years; range: 10-20) with insomnia were administered suvorexant. Clinical background, persistence rate, the Clinical Global Impression (CGI), and the Athens Insomnia Scale (AIS) were compared between patients who continued and discontinued suvorexant treatment. Results: Seventeen patients (56.7%) successfully continued taking suvorexant. Among the 13 patients who did not continue treatment, 5 patients were lost to follow-up. Of the remaining eight who did not continue treatment, four decided to discontinue of their own accord, two decided to discontinue due to lack of effectiveness, and two decided to discontinue due to adverse reaction, namely abnormal dreams. Among patients who completed the study, CGI significantly decreased from 3.6 +/- 0.8 to 3.1 +/- 0.9 (p=0.014). The score of sleep quality in AIS was significantly higher among the patients who discontinued suvorexant than those who continued suvorexant (p=0.02). Conclusion: Our results indicate that suvorexant could be considered a treatment option for adolescents.

DOI： 10.1089/cap.2016.0206

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：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 &lt; 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 &lt; 0.001; CpG2, r = -0.510, p &lt; 0.001; CpG3, r = -0.504, p &lt; 0.001; CpG4, r = -0.356, p &lt; 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. (C) 2017 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jpsychires.2017.04.003

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Language：Japanese   Publisher：(公社)日本精神神経学会  

【目的】インターネットは急速に普及し,生活に必要不可欠なものとなりつつある一方,インターネット使用の制御が困難となるインターネット依存が社会的問題になっている.本研究では,中学生におけるインターネット依存の有病率を調査し,インターネット依存と精神的問題の関連および要因の特定を目的とした.【方法】12〜15歳の中学生874名を対象に,インターネット依存度テスト(IAT),日本語版精神健康調査質問紙短縮版30項目(GHQ)に加え,電子機器の使用状況に関する質問紙を行った.【結果】中学生853名(回収率97.6%,男子425名,女子428名)から回答を得た.IATの平均総得点は32.4±13.6(男子31.4±13.2,女子33.3±13.9)であった.IATの重症度分類では,addictedが2.0%(男子2.1%,女子1.9%),possibly-addictedが21.7%(男子19.8%,女子23.6%)であった.IATの得点に影響する因子は,学年(P=0.001)とGHQ総得点(P&lt;0.001)が有意であった.GHQの平均総得点は,addictedが12.9±7.4,possibly-addictedが8.8±6.0,non-addictedが4.3±4.6であり,依存傾向があるaddictedおよびpossibly-addictedはnon-addictedより有意に得点が高く,問題を抱えた生徒の割合が多かった.また,スマートフォンを自由に使用できることがインターネット依存と関連があった.【考察】インターネット依存の有病率は,possibly-addictedを含め中学生の23.7%にみられ,精神的問題との関連が考えられた.インターネットの適切な利用に関して,保護者,教育機関,医療機関がそれぞれ注意する必要がある.(著者抄録)

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：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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Language：English   Publishing type：Research paper (scientific journal)   Publisher：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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Language：Japanese   Publisher：(公社)日本精神神経学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：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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Language：Japanese   Publisher：(有)科学評論社  

症例は18歳女性で、17歳頃から幻聴が絶えず出現し、被害念慮が増悪したため、アリピプラゾールによる薬物療法を開始したが、症状に改善を認めず、入院となった。絵画欲求不満テストでは、場面状況理解は悪く、場面に関係なく自責的な反応を多く認め、柔軟な対応が困難であることが分かった。会話はオウム返しが多く、周囲の話題についていけないといった社会的コミュニケーションの障害を認め、飲み物の温度に関するこだわり、感覚刺激に対する過敏さといった限局的反復的な行動パターンを認め、DSM-5による自閉症スペクトラム症(ASD)の診断基準を満たした。現在までの行動観察と心理検査結果を総合し、ASDに精神病症状が併存する状態であると診断した。本人に対しては、苦手なところをどう補っていくのかを具体的に伝えるなどした。

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Language：Japanese   Publisher：(株)世論時報社  

バウム・テストは臨床場面において一般的に用いられる投影法だが、自閉スペクトラム症(Autism Spectrum Disorders:ASD)児にバウム・テストを用いた先行研究は多くない。本研究はASD児に併存する抑うつ状態を検出できる指標を明らかにすることを目的に、抑うつ状態ありと児童精神科医が判断したASD児を対象として、バウム・テストとバールソン児童用抑うつ性尺度(Birleson Depression Self-Rating Scale for Children:DSRS-C)を実施し、臨床症状を反映しえるか検討した。その結果、DSRS-Cの総点はASD児の抑うつ状態の有無によって有意差を認めず、バウム・テストの気分の落ち込みを示す指標は、抑うつ状態を伴うASD群で出現数が有意に多かった。バウム・テストの気分の落ち込みを示す指標の出現が、ASD児の抑うつ状態の検出に有用である可能性が示された。(著者抄録)

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：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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Language：Japanese   Publisher：(株)医学書院  

注意欠如・多動症(ADHD)は生涯にわたる障害であるが,成人期におけるADHDの診断は小児期より困難をきわめる。本研究では,標準注意検査法(CAT)を用いて,成人期ADHDの注意機能の特徴を明らかにすることを目的に調査を行った。当院外来を受診した18歳以上の知的障害を伴わないADHD患者を対象とし,認知機能検査としてWAIS-IIIを,注意機能検査としてCATを実施した。CAT各検査結果とWAIS-III全検査IQとの関連について検討し,標準化データと比較検討した。CATの各課題のうち,知的機能の影響を受けず注意障害を認めたものは,Visual Cancellation Task, Auditory Detection Task, PASATであった。成人期ADHDでは視覚的・聴覚的な選択性注意,ワーキングメモリーが特徴的に障害されることが示唆された。(著者抄録)

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J00749&link_issn=&doc_id=20170608060018&doc_link_id=10.11477%2Fmf.1405205390&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1405205390&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

Language：English   Publishing type：Research paper (scientific journal)   Publisher：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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Language：English   Publishing type：Research paper (scientific journal)   Publisher：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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Language：English   Publishing type：Research paper (scientific journal)   Publisher：IOS PRESS  

Microglial dysfunction and inflammation have recently been shown to be related to the development of Alzheimer's disease (AD). Inositol polyphosphate-5-phosphatase (INPP5D) functions broadly as a negative regulator of immune signaling, and its locus was associated with development of AD in a large-scale genome-wide association study. Thus, we examined INPP5D mRNA expression and methylation rates of the CpG sites in the upstream region of INPP5D exon 1 in peripheral leukocytes in 50 AD and age- and sex-matched control subjects. INPP5D mRNA expression in AD subjects was significantly higher than that in control subjects (1.16 +/- 0.39 versus 1.0 +/- 0.23, p = 0.049) and was correlated with the Mini-Mental State Examination score (p = 0.002, r = 0.426) and the total score of the Alzheimer's Disease Assessment Scale (p &lt; 0.001, r = -0.697). Methylation rates in the upstream region of INPP5D exon 1 were not significantly different between AD and control subjects (average rate: 3.5 +/- 3.0 versus 2.8 +/- 1.3, p = 0.551). Our results suggested that INPP5D mRNA expression was elevated in the early stage and decreased with cognitive decline in AD. INPP5D mRNA expression in leukocytes may be a useful biomarker for the early stage of AD.

DOI： 10.3233/JAD-161211

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Background: TOMM40 is located on chromosome 19, is in linkage disequilibrium with apolipoprotein E (APOE), and is 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 &lt; 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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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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Here we report de novo non-synonymous single-nucleotide variants (SNVs) by conducting whole exome sequencing of 18 trios consisting of Japanese patients with sporadic schizophrenia and their parents. Among nine SNVs, we explored the functional impact of the de novo mutation in TBL1XR1 [c.30 C > G (p.Phe10Leu)], a gene previously found to be associated with autism spectrum disorder and epilepsy. Protein structural analysis revealed that Phe10Leu mutation may decrease the structural stability of the TBL1XR1 protein. We demonstrate that Phe10Leu mutation alters the interaction of TBL1XR1 with N-CoR and β-catenin, which play critical roles in regulation of Wnt-mediated transcriptional activity. Consistently, TBL1XR1-mediated activation of Wnt signaling was up-regulated by Phe10Leu mutation. These results suggest that a de novo TBL1XR1 point mutation could alter Wnt/β-catenin signaling activity. Further studies are required to clarify the involvement of TBL1XR1 mutations in neuropsychiatric conditions.

DOI： 10.1038/s41598-017-02792-z

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DOI： 10.3389/fnins.2017.00275

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

BackgroundAutism spectrum disorders (ASD) are characterized by persistent deficits in social communication and social interaction across contexts, and are associated with restricted patterns of behavior. The developmental quotient (DQ) is based on the developmental age and chronological age of children. This study investigated the utility of the DQ to estimate cognitive ability in young children with ASD.
MethodsThe DQ and intelligence quotient (IQ) were assessed using the Kyoto Scale of Psychological Development 2001 (KSPD) and Wechsler Intelligence Scale for Children-III (WISC-III), respectively. The correlation between the DQ and IQ was then analyzed among children with ASD.
ResultsWe enrolled 18 children with ASD (16 boys, two girls; age, 63.6 9.4 months; age range, 45-83 months). Overall, Cognitive-Adaptive and Language-Social DQ scores were significantly correlated with IQ score in the full scale, verbal, and performance domains. Full-scale IQ and overall DQ had a linear correlation (y = -22.747 + 1.177x, R-2 = 0.677, R = 0.823).
ConclusionsThe DQ scores obtained using the KSPD were a reasonable estimate of cognitive ability in children with ASD. The KSPD may be a useful alternative to the WISC-III for young children with ASD and could facilitate earlier assessment.

DOI： 10.1111/ped.12969

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Language：Japanese   Publisher：(株)三原医学社  

2014年11月に、愛媛県伊予郡松前町内の公立中学校3校に在籍する生徒874名を対象に、地域の中学生においてインターネットの利用・依存が睡眠習慣に与える影響について調査し検討した。最終的な有効回答は853名(男子425名、女子428名、平均13.6±0.9歳)であった。IATスコアによる重症度分類では依存状態が2.0%、依存傾向が21.7%であった。重症が高い即ち依存傾向が強いほど、睡眠の問題が有意に多く、平日の睡眠時間・就寝時刻、休日の起床・就寝時刻に群間差を認め、インターネット依存と睡眠習慣・睡眠衛生への関与が示唆された。

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

AimInternet addiction disrupts the daily lives of adolescents. We investigated the prevalence of Internet addiction in junior high school students, elucidated the relation between Internet addiction and mental states, and determined the factors associated with Internet addiction in adolescents.
MethodsJunior high school students (aged 12-15 years) were assessed using Young's Internet Addiction Test (IAT), the Japanese version of the General Health Questionnaire (GHQ), and a questionnaire on access to electronic devices.
ResultsBased on total IAT scores, 2.0% (male, 2.1%; female, 1.9%) and 21.7% (male, 19.8%; female, 23.6%) of the total 853 participants (response rate, 97.6%) were classified as addicted and possibly addicted, respectively. Total GHQ scores were significantly higher in the addicted (12.9 7.4) and possibly addicted groups (8.8 +/- 6.0) than in the non-addicted group (4.3 +/- 4.6; P &lt; 0.001, both groups). A comparison of the percentage of students in the pathological range of GHQ scores revealed significantly higher scores in the possibly addicted group than in the non-addicted group. Further, accessibility to smartphones was significantly associated with Internet addiction.
ConclusionStudents in the addicted and possibly addicted groups were considered problematic' Internet users. Use of smartphones warrants special attention, being among the top factors contributing to Internet addiction.

DOI： 10.1111/pcn.12402

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Yoshino Y, Mori T, Yoshida T, Yamazaki K, Ozaki Y, Sao T, Funahashi Y, Iga JI, Ueno SI, Journal of Alzheimer&#039;s disease : JAD, 2016, 2016

DOI： 10.3233/JAD-160430

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DOI： 10.1080/15622975.2016.1197424

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Language：Japanese   Publisher：(一社)日本睡眠学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BIOMED CENTRAL LTD  

Backgrounds: Suicide is a leading cause of death in adolescence. Effective strategies are required to prevent suicide. We aimed to assess the prevalence of suicidal ideation in early teens and the relationship between family mental health and suicidal ideation of their child.
Methods: A population-based survey in a rural town included 185 junior high school students and their caregivers. Suicidal ideation and mental states were assessed with General Health Questionnaire (GHQ) and Profile of Mood States (POMS) form.
Results: Nineteen (10.3 %) students experienced suicidal ideation in the preceding weeks and had more mental health problems than students without suicidal ideation. Caregivers of students with suicidal ideation demonstrated significantly higher suicidal depression scores in GHQ. Multivariate logistic regression analysis revealed that suicidal depression of caregivers was the most important factor for suicidal ideation of students.
Conclusions: Suicidal ideation of children is associated with suicidal depression of their caregivers. For the prevention of suicide in adolescents, not only their own mental status but also that of caregivers should be taken into consideration.

DOI： 10.1186/s12888-016-0934-2

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DOI： 10.1159/000447324

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Language：Japanese   Publisher：(公社)日本精神神経学会  

神経発達障害,主に注意欠如・多動症(ADHD)や自閉スペクトラム症(ASD)に関連する睡眠障害には,生来性の睡眠の量や質の低下,睡眠覚醒リズムの構築異常,発達障害に並存する睡眠障害,発達障害の二次障害としての睡眠障害,二次障害の一症状としての睡眠障害,さらに発達障害の薬物治療に伴う睡眠障害があり多因子である.小児ADHDとの関連が深い睡眠障害としては,閉塞性睡眠時無呼吸症候群(OSAS)やレストレスレッグス症候群(RLS)が挙げられる.小児のOSASは低身長や認知機能・行動の問題,ADHD様症状や夜尿の遷延などの症状がみられる.アデノイド・扁桃腺肥大によるものが多く,外科的処置が第一選択となる場合が多い.ADHDとRLSでは共通して鉄欠乏やドパミン系の異常の関与が指摘され,合併頻度は予想以上に高い.RLSでは一般的に睡眠薬は無効であり,的確な診断が重要となる.小児ASDと関連の深い睡眠障害としては,不眠障害,睡眠時随伴症および概日リズム睡眠-覚醒障害などが挙げられる.発達障害児の不眠やリズム障害に対しては睡眠衛生指導や行動療法的介入が一般的であるが,薬物治療も必要となる場合がある.実臨床では眠気が目立ち,低覚醒状態ではないかと思われる発達障害児に遭遇する.発達障害児は過覚醒状態・低覚醒状態・混合状態であるとの説が存在し,今後発達障害と覚醒度との関連は注目すべきポイントである.ADHD治療薬である中枢神経刺激薬は不眠の原因ともなりうるが,逆にADHD症状の改善に伴い睡眠が改善するとの報告もある.一方,非中枢神経刺激薬は不眠を改善する場合があり,併存する睡眠の問題を考慮して診療する必要があるが,さらなる検討を要する.以上のように,睡眠障害が発達障害の症状を増幅している場合があり,睡眠障害の治療により発達障害の症状が軽減しうる可能性がある.睡眠障害をも念頭において,発達障害の日常診療を行う必要がある.(著者抄録)

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DOI： 10.1017/S1041610215001763

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

Anorexia nervosa (AN) is a complex psychiatric disorder, which is not yet fully understood. Several studies reported that AN was associated with disruption of cytokine network. Carcinoembryonic antigen (CEA) is a glycoprotein related to its network, used as a tumor marker of adenocarcinoma, and suggested to stimulate monocytes and macrophages to release proinflammatory cytokines. Here, we report a 41-year-old male suffering from AN who was suspected of having a malignant tumor due to markedly elevated serum CEA levels. However, on further examinations, he was discovered to have no malignant tumors, and, interestingly, his CEA levels actually decreased as his clinical state of AN improved. Furthermore, it was found that his CEA levels were elevated proportionally to his clinical state of AN and that his body mass index was significantly correlated with serum CEA levels. Therefore, it is suggested that inflammatory responses may be associated with the clinical state of AN. (c) 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:428-431).

DOI： 10.1002/eat.22474

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DOI： 10.1007/s00702-016-1560-3

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Other Link： http://orcid.org/0000-0003-4409-3096

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Clozapine-induced agranulocytosis (CIA)/clozapine-induced granulocytopenia (CIG) (CIAG) is a life-threatening event for schizophrenic subjects treated with clozapine. METHODS: To examine the genetic factor for CIAG, a genome-wide pharmacogenomic analysis was conducted using 50 subjects with CIAG and 2905 control subjects. RESULTS: We identified a significant association in the human leukocyte antigen (HLA) region (rs1800625, p = 3.46 × 10(-9), odds ratio [OR] = 3.8); therefore, subsequent HLA typing was performed. We detected a significant association of HLA-B*59:01 with CIAG (p = 3.81 × 10(-8), OR = 10.7) and confirmed this association by comparing with an independent clozapine-tolerant control group (n = 380, p = 2.97 × 10(-5), OR = 6.3). As we observed that the OR of CIA (OR: 9.3~15.8) was approximately double that in CIG (OR: 4.4~7.4), we hypothesized that the CIG subjects were a mixed population of those who potentially would develop CIA and those who would not develop CIA (non-CIA). This hypothesis allowed the proportion of the CIG who were non-CIA to be calculated, enabling us to estimate the positive predictive value of the nonrisk allele on non-CIA in CIG subjects. Assuming this model, we estimated that 1) ~50% of CIG subjects would be non-CIA; and 2) ~60% of the CIG subjects without the risk allele would be non-CIA and therefore not expected to develop CIA. CONCLUSIONS: Our results suggest that HLA-B*59:01 is a risk factor for CIAG in the Japanese population. Furthermore, if our model is true, the results suggest that rechallenging certain CIG subjects with clozapine may not be always contraindicated.

DOI： 10.1016/j.biopsych.2015.12.006

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Language：Japanese   Publishing type：Research paper (scientific journal)  

Neurodevelopmental disorders, including attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), are commonly associated with sleep disturbances. The etiology of sleep disorders is multifactorial, such as congenital vulnerability of the quality and quantity of sleep, congenital abnormality of the sleep-wake pattern, comorbid sleep problems with developmental disorders, and sleep disturbances associated with pharmacological treat- ment. Obstructive sleep apnea disorder (OSAS) and restless legs syndrome (RLS) are closely associated with ADHD. OSAS in children not only presents with symptoms of sleep distur- bances, but also with associated symptoms such as growth failure, neurocognitive and behav- ioral symptoms, ADHD-like symptoms, and enuresis. The first-line treatment is adenotonsillec- tomy. ADHD and RLS show high rates of comorbidity with common etiologies like iron defi- ciency and the alternation of dopamine transporter expression. Hypnotics are not effective for RLS, and a precise diagnosis is vital to treat RLS associated with ADHD. ASD is also associated with a high frequency of sleep disorders, especially insomnia, para- somnia, and sleep-wake disorders. The first strategy against sleep disturbances is behavioral intervention ; however, pharmacological treatment is sometimes needed. In clinical practice, excessive daytime sleepiness was reported in children with ADHD or ASD, which might lead to a deficit in alertness. Alertness deficits associated with neurodevel- opmental disorders remain uncertain, and so they should be assessed. The effect of stimulants on sleep in patients with ADHD differed among individuals, which might be the cause of insomnia and also treatment for ADHD and sleep hygiene. Non-stimu- lants are often effective for insomnia. Neurodevelopmental and sleep disorders are complex and bidirectional. Sleep disturbances should be taken into consideration in daily clinical practice.

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DOI： 10.9758/cpn.2015.13.3.324

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

Objective: This aim of this study was to examine the mechanisms underlying the neuropsychiatric symptoms in dementia with Lewy bodies by investigating regional cerebral blood flow.
Methods: Participants were 27 patients who fulfilled the diagnostic criteria for probable dementia with Lewy bodies. All subjects underwent single-photon emission computed tomography scans using technetium-99m hexamethylpropyleneamine oxime. Neuropsychiatric symptoms were evaluated by neuropsychiatric inventory. Multiple regression analyses using neuropsychiatric inventory and voxel-based analyses of covariance of the regional cerebral blood flow images between subjects with or without each neuropsychiatric symptom were performed. Additionally, similar voxel-based analyses of covariance between subjects with each neuropsychiatric symptom and normal subjects were performed.
Results: There were no significant correlations in any psychiatric symptoms in multiple regression analyses. All subjects had hallucination but none had euphoria. We analyzed eight neuropsychiatric symptom scores with the exception of hallucination and euphoria using voxel-based analyses of covariance. Significant differences of regional cerebral blood flow were shown in groups with agitation, disinhibition, and irritability. Subjects with agitation showed hypoperfusion in the parietal lobule, the precuneus, and the angular gyrus, and hyperperfusion in the fusiform gyrus, the lingual gyrus, and the thalamus. Subjects with disinhibition showed hypoperfusion in the left frontal gyrus. Subjects with irritability showed hyperperfusion in the right frontal gyrus. There were no significant differences in regional cerebral blood flow between subjects with any neuropsychiatric symptoms and normal subjects.
Conclusion: This study reveals that dysfunction of specific brain regions is associated with various neuropsychiatric symptoms in dementia with Lewy bodies. Copyright (C) 2015 John Wiley & Sons, Ltd.

DOI： 10.1002/gps.4263

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Common adverse effects of atypical antipsychotic treatments for schizophrenia are weight gain and lipid metabolism abnormality. We aimed to identify the signs of metabolic problems with continuous atypical antipsychotic treatment for schizophrenia over a 2-year period. METHODS: The participants were 68 schizophrenic patients (29 males, 39 females; ages 53.4 ± 13.5 years old). Changes in carbohydrate metabolism and changes in physical characteristics were studied over a 2-year period. In addition, functional single nucleotide polymorphisms in the transcriptional regulatory region of the resistin gene were examined. RESULTS: We found no changes in the mental state of the participants over a 2-year period. Patients did show a significant decrease in total cholesterol and hemoglobin A1c levels, although physical changes such as body mass index and abdominal girth, were not observed. The amount of resistin may not be associated with mental states and physical parameters. CONCLUSIONS: We could not find physical factors related to metabolic changes of antipsychotics in this 2-year study. However, several psychological factors, such as health-related thoughts and behaviors, should be studied in the future.

DOI： 10.1177/2045125315596697

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Language：Japanese   Publisher：(株)三原医学社  

2014年度に愛媛県久万高原町の全中学生を対象に、夏季休暇時期に生活習慣についてのワークブックを作成し、その取り組みおよび介入効果について検討した。夏季休暇開始1週間前に学校担任からワークブックを配布してもらい、配布日の夜から記入を開始し、夏季休暇終了後1週間目までの記入を依頼した。全中学生204名のうち、171名(中学1年生49名、中学2年生60名、中学3年生62名)からワークブックを回収することができた。ワークブックへの記入を実施した後のアンケート(有効回答137名)では、「頑張って取り組めた」15.3%、「まずまず取り組めた」42.3%、「あまり取り組めなかった」19.0%、との回答であった。睡眠改善の課題についての自覚的達成感について尋ねたところ、「達成できた」「やや達成できた」と、規則正しい生活の確立で72%、光環境の調整で52%、メディア環境の調整で53%が回答した。中学生自身が記入するワークブックは、睡眠改善などに有効なことが示唆された。

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER IRELAND LTD  

Nitric oxide (NO) may be a neurotransmitter related to major depressive disorder (MDD) because the selective neuronal NO synthase (NOS) inhibitor, 7-nitroindazole, induces dose-dependent antidepressant-like effects. However, its role in MDD is not yet known. The purpose of our study was to determine if antidepressants improve depression via the NO pathway using an acute depressive rat model induced by L-arginine (AR). Three types of antidepressants were examined, fluoxetine (FLX, 10 mg/kg), milnacipran (MIL, 30 mg/kg), and mirtazapine (MIR, 10 mg/kg), in a depressive model that used AR (750 mg/kg) pretreatment. mRNA expression levels of three NOS subtypes were analyzed by real-time PCR, as well as serum NO levels. Significant increases in iNOS mRNA expression levels were found in brain regions after AR treatment, although the eNOS gene tended to decrease with AR injection. After antidepressant treatment, there were no mRNA expression changes in either nNOS or iNOS. However, eNOS mRNA expression significantly increased with FLX (cerebellum, P = 0.011; hippocampus, P = 0.011; midbrain, P = 0.011; pons, P = 0.013; striatum, P = 0.011; and thalamus, P &lt; 0.001). There was a statistically significant increase in serum NO levels with MIL treatment (P = 0.011). We conclude that changes in eNOS mRNA levels in the brain with FLX treatment, and amount of serum NO with MIL treatment may be related to antidepressant effects of both agents, but further experiments are needed to confirm involvement of the NO system in MDD. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.neulet.2015.05.043

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER WIEN  

Abnormal hexanucleotide repeat expansion of C9ORF72 is known to cause neurodegenerative disorders such as frontotemporal dementia. Additionally, patients with psychotic symptoms are more likely to have abnormal hexanucleotide repeat expansion than are patients without them. We investigated the hexanucleotide repeat sizes of C9ORF72 in 466 Japanese schizophrenia patients. We found no abnormal hexanucleotide repeat expansion. In conclusion, C9ORF72 may not be responsible for schizophrenia susceptibility in the Japanese population.

DOI： 10.1007/s00702-014-1295-y

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Language：Japanese   Publisher：(公社)日本精神神経学会  

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Language：Japanese   Publisher：愛媛医学会  

【目的】昨今、発達障害者に対する就労支援の関心も高まりつつある。発達障害者の現場での就労状況について実態を把握することを目的に、事業所スタッフを対象とした実態調査を行った。【対象と方法】2013年8〜12月の期間、愛媛県内の専属産業医を選任している事業所8ヶ所に勤務する産業医及び人事労務管理担当者を対象に対面での聞き取り調査を行った。【結果】対象事業所は5ヶ所で、発達障害者の雇用をしている事業所は1ヶ所、過去に雇用経験がある事業所は2ヶ所であった。これら3ヶ所の事業所で雇用されている、もしくはされていた発達障害者は、メンタルヘルス不調で休職後に広汎性発達障害と診断された。【考察】メンタルヘルス不調をおこした発達障害者に対し、不調の根底にあるであろう障害特性への対応を早期に行うことが望ましい。当事者と会社が障害特性を把握し、その特性を考慮した環境調整が必要であることを両者が理解する必要がある。発達障害者の雇用増加に備え、適切な対応が期待される。(著者抄録)

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Language：Japanese   Publisher：愛媛医学会  

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DOI： 10.1371/journal.pone.0136835

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Other Link： http://orcid.org/0000-0003-4409-3096

Language：Japanese   Publisher：(株)アークメディア  

2010年4月1日から2012年3月31日迄にA児童発達支援センターに通所した児童のうち、毎日(週5)通所しており、難聴児・肢体不自由児を除く91名(男児75名、女児16名)を対象に、児童の養育者および児童指導員双方からみた児童の精神健康状態の認識の違いを明らかにするために、強さと困難さ質問票(Strengths and Difficulties Questionnaire:SDQ)を用いた調査を行った。地域の児童と比較して児童発達支援センターに通所する児童は男女ともSDQにおける殆どの下位尺度(情緒面、多動・不注意、仲間関係、向社会性)で困難さが存在し、支援の必要性が高いと考えられた。男児のSDQ「総スコア」および下位尺度の「多動・不注意」において、児童指導員は養育者よりも支援の必要性を有意に高いと認識していることが分かった。女児に関しては養育者と児童指導員の比較で有意差を認めなかった。SDQは児童の困難さを数値化し表すことができ、養育者と教師が共通理解を得るために役立つことが示唆された。

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2014&ichushi_jid=J01552&link_issn=&doc_id=20141209140015&doc_link_id=%2Fao1clphd%2F2014%2F004312%2F016%2F1811-1819%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fao1clphd%2F2014%2F004312%2F016%2F1811-1819%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：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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Language：English   Publishing type：Research paper (scientific journal)   Publisher：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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Language：English   Publishing type：Research paper (scientific journal)   Publisher：KOREAN COLL NEUROPSYCHOPHARMACOLOGY  

Clozapine is well known for successful use in schizophrenic patients treatment resistant to other antipsychotics. However, even with clozapine, 25% of schizophrenic patients are not in remission. Recently, as adjunctive treatment with clozapine, electroconvulsive therapy has been reported to be an effective and safe adjunctive treatment. We report a Japanese schizophrenic woman who was not in remission with clozapine alone but with both clozapine and electroconvulsive therapy.

DOI： 10.9758/cpn.2014.12.2.160

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

Alanine:glyoxylate aminotransferase 2 (AGXT2) is the only enzyme that degrades D-3-aminoisobutyrate (D-AIB), which is an intermediate product of thymine, and 30-40% of Japanese lack AGXT2 activity genetically and excrete high amounts of D-AIB in their urine. Recently, AGXT2 is reported to metabolize asymmetric dimethyl arginine (ADMA), a competitive inhibitor of nitric oxide (NO) synthase. Since AGXT2 is expressed in the central nervous system, the loss of AGXT2 activity will be related to the vulnerability for neuropsychiatric disorders related to the NO system. In this study, we recruited 85 Japanese subjects to discover loss variants of the AGXT2 gene with the amount of D-AIB excretion in their urine. From the statistical relevance between them, we found three missense polymorphisms (rs37370, rs37369, and rs180749) independently related to AGXT2 activity (P &lt; 0.0001). Then, we performed a case-control association analysis of its missense polymorphisms with 1136 schizophrenia and 1908 control subjects because the NO system may be involved in the vulnerability of schizophrenia processes. We could not find any associations of three functional SNPs with schizophrenia pathogenesis in the analyses of either genotypic or allelic models. We concluded that the AGXT2 gene is not associated with schizophrenia in Japanese subjects. (C) 2014 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.pnpbp.2014.04.002

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Language：Japanese   Publisher：(株)医学書院  

自殺に関する意識の高い愛媛県久万高原町において,若年者の自殺予防対策の一環として,中学生のメンタルヘルスの実態を明らかにすることを目的に,日本語版Profile of Mood States-Brief Formと日本版精神健康調査質問票を用いて調査を行った。町内全生徒220名から回答を得た。全体の傾向として,中学2,3年で精神的不調の訴えが多かったが,女子で特にその傾向が強かった。抑うつ感情は中学2,3年の女子が男子に比し有意に高く,自殺しようと考えたことがあると回答した生徒は男子9名,女子12名で計21名(9.5%)であった。自殺予防の観点から,特に中学2,3年女子に一定の配慮が必要であると思われた。今後,縦断的な自殺対策活動と支援体制の確立が必要である。(著者抄録)

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2014&ichushi_jid=J00749&link_issn=&doc_id=20140808060003&doc_link_id=10.11477%2Fmf.1405102754&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1405102754&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

Aim: Children with autism spectrum disorders (ASD) often present with emotional and behavioral problems, which could change the clinical course, especially during childhood, and affect future quality of life. The aim of this study was to clarify the age- and sex-related differences of these problems in ASD.
Methods: The study subjects were 173 patients with ASD (age: 4-16 years) and 173 age-and sex-matched community children (control group). The parent version of the Strengths and Difficulties Questionnaire was used for comparison of the emotional and behavioral problems between the two groups.
Results: The Strengths and Difficulties Questionnaire scores were significantly higher in children with ASD than controls at all ages. The score of total difficulties was significantly higher in girls with ASD than in boys, while the score in male controls was significantly higher than in female controls. Age-related differences in emotional and behavioral problems were observed both in children with ASD and controls, but the characteristics were different: in children with ASD, emotional symptoms and peer problems in both sexes and conduct problems in girls increased significantly with age, while none of the problems in the controls changed with age except for a decrease in the score of hyperactivity/inattention developmentally in both sexes. Prosocial behaviors of children with ASD and controls showed small changes with age.
Conclusion: Emotional and behavioral problems are common in children with ASD and showed age-and sex-related differences. Our study emphasizes the importance of recognizing those differences among children with ASD for early intervention.

DOI： 10.1111/pcn.12164

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Language：Japanese   Publisher：(株)星和書店  

成人期の注意欠如・多動性障害(Attention-Deficit/Hyperactivity Disorder:ADHD)の治療においては、効果判定は主観的な臨床評価によっており、客観的な評価方法は確立されていない。今回我々は、atomoxetineを用いた成人期ADHD患者の診断・治療効果判定に、客観的臨床評価手法として標準注意検査法(Clinical Assessment for Attention:CAT)を使用し、臨床経過をよく反映した1例を経験したので報告する。症例は40歳女性、中学時代から学校への忘れ物が多く、集中力がないことを自覚し始めた。21歳時にうつ病と診断されていたが、40歳時に発達障害を疑われ当院に紹介された。改めて病歴聴取を行い、学童期以降のADHD症状を確認し、CATの結果も参考にしながら、ADHDとの診断に至った。Atomoxetineを40mg/日から内服開始し、80mg/日に増量したところ、日常生活およびCATでの評価における不注意症状の改善を認めた。成人期ADHDでは、不注意が生活の障害となることが多いが、CATは、ADHDの不注意症状を反映する可能性があると思われた。(著者抄録)

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Language：Japanese   Publisher：(株)世論時報社  

【目的】本研究は愛媛大学医学部附属病院精神科の児童青年期精神科部門における外来診療の10年間の変遷を明らかにすることを目的に調査を行った。【方法】2002年と2012年の1年間の18歳以下の初診患者を対象に、性別、初診時年齢、受診経路、主訴・主症状、診断、転帰について診療録に基づいて後方視的に比較検討を行った。【結果】2002年と比較し2012年では18歳以下の初診患者の増加、患者の低年齢化、紹介率の増加、発達障害と診断される患者の増加を認めた。主訴として最も多かった不登校に関して、契機と発達障害の有無について追加調査したところ、発達障害を伴う不登校は伴わない不登校と比べ男性に多く、低年齢の傾向があった。【考察】精神科医療を必要とする児童青年期患者の増加に伴い、より専門的な診療体制を整えることが必要である。また、発達障害に関する精査や発達障害を伴う不登校の増加から、医療・教育・福祉、さらには就労も視野に入れた連携と強化が必要と考えられた。(著者抄録)

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER IRELAND LTD  

Delayed carbon monoxide (CO) encephalopathy may occur following recovery from acute CO poisoning. However, the mechanism of delayed neuronal injury remains unknown. The nicotinic acetylcholine receptors (nAChRs) have been suggested to play a role in cognitive status in neurodegenerative diseases, including Alzheimer's disease. Therefore, in the current study, we investigated the effect of delayed neuronal CO poisoning on gene expression of nAChRs in the hippocampus of Wistar rats. Behavioral effects (measured by the passive-avoidance test) and histological analyses (hematoxylin-eosin-stained hippocampal cell counts and cell death observations) were also investigated, 21 days after CO exposure for I h (1000 ppm for 40 min + 3000 ppm for 20 min). Our findings show cognitive impairment and hippocampal cell death, suggesting our rat model is suitable for studying delayed CO encephalopathy. Expression of nAChR (Chrna3, Chrna4, Chnra7, and Chrnb2) mRNA was assessed using quantitative real-time polymerase chain reaction. Hippocampal Chrna3 expression was significantly decreased, and cerebellar Chrna7 expression significantly increased, in the delayed CO encephalopathy rat model. Thus, the nicotinic cholinergic system may be affected in delayed CO encephalopathy. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.neu1et.2014.03.054

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Language：English   Publisher：KOREAN COLL NEUROPSYCHOPHARMACOLOGY  

Acute pancreatitis with antipsychotic treatment is rare but sometimes causes a fatal adverse effect. Most cases of acute pancreatitis due to atypical antipsychotic agents are reported to occur within six months of starting antipsychotic administration. Acute pancreatitis caused by risperidone is rare. The patient had a high fever, stomachache and vomiting. The results of the abdominal computed tomograhpy scan were negative. The results of the abdominal ultrasonography were positive for gallstones in gallbladder and distention of the common bile duct. She had been fasting and received antibiotic intravenous injections. Amylase and lipase titers were high. After risperidone discontinuation, both the levels of the amylase and the lipase were gradually decreased. Three months later, the patient still maintains a good clinical balance. Although atypical antipsychotic-induced pancreatitis has been reported in conjunction with hyperglycemia, the pathophysiologic mechanism of these adverse events remains unclear. This case got pancreatitis 6 month after risperidone treatment. Using the antipsychotic agents, it is necessary to monitor pancreas function.

DOI： 10.9758/cpn.2014.12.1.67

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BMJ PUBLISHING GROUP  

Objective Neuropsychiatric symptoms affect many patients with Alzheimer's disease (AD). (C-11)Pittsburgh Compound-B (PIB) positron emission tomography (PET) has enabled the in vivo visualisation of brain amyloid- (A) deposition. This study exploratively investigated the correlation between brain A deposition measured by (C-11)PIB PET and neuropsychiatric symptoms in AD.
Methods Participants were 28 patients (15 women, 13 men) with PIB-positive AD. Clinical assessments included Mini-Mental State Examination, Clinical Dementia Rating scale, neuropsychiatry inventory (NPI) and frontal assessment battery. All patients underwent three-dimensional T1-weighted MRI and (C-11)PIB PET. The distribution volume ratio (DVR), an index of (C-11)PIB retention and, thus, A deposition, was estimated voxel by voxel from (C-11)PIB PET data with partial volume correction. Voxel-based correlation analysis was performed to assess the relationships between DVR and each NPI subscale. Additionally, voxel-based analysis of covariance (ANCOVA) of the DVR images was performed between Patients with AD with and without each neuropsychiatric symptom. Voxel-based morphometry analysis of MRI was also performed.
Results Apathy subscale was correlated with (C-11)PIB retention in the bilateral frontal and right anterior cingulate. (C-11)PIB retention was greater in the bilateral frontal cortex of patients with AD with apathy than those of without apathy. Overlapping areas between the two analyses were the bilateral orbitofrontal gyrus and left superior frontal gyrus. Other NPI subscales were not correlated with (C-11)PIB retention. Voxel-based morphometry analysis of MRI showed no significant cluster of correlation between grey matter volume and NPI subscales.
Conclusions This study revealed that prefrontal A deposition correlates with apathy.

DOI： 10.1136/jnnp-2013-306110

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BIOMED CENTRAL LTD  

Background: D-3-aminoisobutyrate, an intermediary product of thymine, is converted to 2-methyl-3-oxopropanoate using pyruvate as an amino acceptor by D-3-aminoisobutyrate-pyruvate aminotransferase (D-AIB AT; EC 2.6.1.40). A large amount of D-AIB AT is distributed in the kidney and liver; however, small amounts are found in the brain. Recently, D-AIB AT was reported to metabolize asymmetric dimethylarginine (ADMA) in vivo and was suggested to be an important enzyme for nitric oxide metabolism because ADMA is a competitive inhibitor for nitric oxide synthase. In this study, we examined the distribution of D-AIB AT in the rat brain further to understand its role. We measured D-AIB AT mRNA and protein expression using quantitative RT-PCR and Western blotting, and monitored its distribution using immunohistochemical staining.
Results: D-AIB AT was distributed throughout the brain, with high expression in the cortex and hippocampus. Immunohistochemical staining revealed that D-AIB AT was highly expressed in the retrosplenial cortex and in hippocampal neurons.
Conclusion: Our results suggest that D-AIB AT is distributed in the examined-just the regions and may play an important role there.

DOI： 10.1186/1471-2202-15-53

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Language：Japanese   Publisher：(一社)日本高次脳機能障害学会  

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Obstructive sleep apnea syndrome (OSAS) in children does not only present with symptoms of sleep disturbances but also with associated symptoms such as growth failure, enuresis, academic learning difficulties, and behavioral problems, including attention deficit/hyperactivity disorder- (ADHD-) like symptoms. We evaluated neurocognitive functions before and after adenotonsillectomy in a patient with OSAS. An 11-year-old boy suspected of having ADHD with nocturnal enuresis was referred for evaluation. He was found to have adenotonsillar hypertrophy. Presence of snoring was evident only after detailed medical interview. Polysomnography confirmed the diagnosis of OSAS, which was subsequently treated by adenotonsillectomy. The apnea/hypopnea index decreased from 21.9 at baseline to 1.8 after surgery, and the frequency of enuresis fell from almost nightly to 2-3 times per month. Neurocognitive and behavioral assessment after the treatment of OSAS showed significant improvement in cognitive functions, especially attention capacity and considerable amelioration of behavioral problems including ADHD-like symptoms. As the most common cause of pediatric OSAS is adenotonsillar hypertrophy, medical interview and oropharyngeal examination should always be performed in children suspected of having ADHD. The necessity of sleep evaluation for children with ADHD-like symptoms was also emphasized.

DOI： 10.1155/2014/520215

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Language：Japanese   Publisher：The Institute of Electronics, Information and Communication Engineers  

Nanocircuits consisting of materials such as carbon nanotubes have been extensively investigated as promising architechures, since they are relatively easily manufactured. Owing to their small scale, however, nanocircuits are likely to contain many defects, and defect tolerance is an essential issue in their design. We introduce two fundamental problems in the defect-tolerant design of nanocircuits and survey the graph theory associated with the problems.

DOI： 10.1587/essfr.8.30

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DOI： 10.14947/psychono.33.9

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Language：English   Publishing type：Research paper (scientific journal)  

Children with autism spectrum disorders (ASD), including autistic disorder, frequently suffer from comorbid sleep problems. An altered melatonin rhythm is considered to underlie the impairment in sleep onset and maintenance in ASD. We report three cases with autistic disorder in whom nocturnal symptoms improved with ramelteon, a selective melatonin receptor agonist. Insomnia and behavior, assessed using the Clinical Global Impression-Improvement Scale, improved in two cases with 2 mg ramelteon and in the third case with 8 mg ramelteon. Our findings demonstrate that ramelteon is effective not only for insomnia, but for behavioral problems as well, in patients with autistic disorder.

DOI： 10.1155/2014/561071

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：TERMEDIA PUBLISHING HOUSE LTD  

Introduction: Myasthenia gravis (MG) is an antibody-mediated, T-cell-dependent autoimmune disease. The symptoms are caused by high-affinity IgG against the muscle acetylcholine receptor (AChR) at the neuromuscular junction. The production of these antibodies in B-cells depends on AChR-specific CD4(+) T-cells and the thymus gland seems to play a significant role in the pathogenesis of MG. Altered thymic T-cell export seems to be associated with a pathological mechanism in myasthenia gravis. Tacrolimus (FK506) has recently been used to treat MG.
Material and methods: We examined the effects of tacrolimus on thymic T-cell export in patients with MG. Sixteen patients with nonthymomatous and/or thymectomized MG were treated with oral administrations of tacrolimus. To assess the effect of tacrolimus on the thymic output, we assayed the levels of T-cell receptor excision circle (TREC), a molecular marker of thymus emigrants.
Results: T-cell receptor excision circle was not significantly different from those in age-matched controls before tacrolimus therapy, but they were partially decreased 4 months after tacrolimus therapy. T-cell receptor excision circle levels were significantly decreased in the thymomatous group (p &lt; 0.05), but not in the nonthymomatous group. Tacrolimus treatment significantly attenuated TREC levels in cultured CD4(-)CD8(+) cells (p &lt; 0.05), but total cell counts were not significantly changed.
Conclusions: These results indicate that TREC levels may become a marker of the curative effect of tacrolimus therapy for thymomatous MG, and that tacrolimus suppresses not only activating T-lymphocytes, but also naive T-cells.

DOI： 10.5114/aoms.2013.39797

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Language：English   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Objective: Recently, atypical antipsychotic agents have primarily been used in pharmacological treatment of schizophrenia because of the fewer associated adverse effects. Blonanserin is a novel atypical antipsychotic recently introduced to treat patients with schizophrenia in Japan and South Korea. In this study, we examined the efficacy of switching antipsychotic medications to blonanserin monotherapy in patients with chronic schizophrenia with associated hyperprolactinemia.
Methods: Ten schizophrenic patients (5 males and 5 females) with hyperprolactinemia were recruited. Clinical data before (baseline) and 12 weeks after (end point) switching to blonanserin monotherapy were assessed using the Brief Psychiatric Rating Scale score, Drug-Induced Extrapyramidal Symptoms Scale, and serum prolactin levels.
Results: The mean (SD) blonanserin dosage was 14.8 (3.8) mg/d. After switching to blonanserin, there were significant improvements in the Brief Psychiatric Rating Scale in the patients from both sexes. Moreover, serum prolactin levels in the female patients significantly decreased to within reference range. There were no additional adverse effects observed with the blonanserin treatment.
Conclusions: Switching to blonanserin can reverse medication-induced prolactin elevations found in female patients-and blonanserin is a suitable antipsychotic for schizophrenic patients.

DOI： 10.1097/WNF.0000000000000006

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Language：Japanese   Publisher：(公社)日本精神神経学会  

症例は60歳男性で、本人は特に困ることはないと述べており、家族は認知症の精査と体が動くようにして欲しいと望んでいた。50歳頃から近時記憶障害が出現し、近医受診されるが異常は指摘されなかった。56歳頃から失見当識が出現し、59歳時には幻視や着衣失行、散歩中警察に保護された。つじつまの合わない言動や易怒性から精神科病院に入院し、診断および治療目的で転院となった。遺伝子検査においてアミロイド前駆体タンパク遺伝子変異(APPV7171)を認め、若年発症のAlzheimer病と診断した。診断後、抗精神病薬を減量中止し、過鎮静や錐体外路兆候が消失した。donepezilを10mgまで増量し、意欲、活動性が改善した。家族歴が明らかでなく、多彩な精神神経症状を認める若年発症の認知症の診断には、遺伝子検査を行うことで、有益な結果がもたらされる可能性が示唆された。

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2013&ichushi_jid=J00755&link_issn=&doc_id=20131101090002&doc_link_id=40019838319&url=http%3A%2F%2Fci.nii.ac.jp%2Fnaid%2F40019838319&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_1.gif

Language：Japanese   Publisher：(一社)日本言語聴覚士協会  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2013&ichushi_jid=J04306&link_issn=&doc_id=20131007180179&doc_link_id=10.11477%2Fmf.6001100379&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.6001100379&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

Language：Japanese   Publisher：(株)ワールドプランニング  

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Language：Japanese   Publisher：(公社)日本精神神経学会  

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Language：Japanese   Publisher：(公社)日本精神神経学会  

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Language：Japanese   Publisher：(株)ワールドプランニング  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：CELL PRESS  

Oligomeric forms of amyloid-beta peptide (A beta) are thought to play a pivotal role in the pathogenesis of Alzheimer's disease (AD), but the mechanism involved is still unclear. Here, we generated induced pluripotent stem cells (iPSCs) from familial and sporadic AD patients and differentiated them into neural cells. A beta oligomers accumulated in iPSC-derived neurons and astrocytes in cells from patients with a familial amyloid precursor protein (APP)-E693 Delta mutation and sporadic AD, leading to endoplasmic reticulum (ER) and oxidative stress. The accumulated A beta oligomers were not proteolytically resistant, and docosahexaenoic acid (DHA) treatment alleviated the stress responses in the AD neural cells. Differential manifestation of ER stress and DHA responsiveness may help explain variable clinical results obtained with the use of DHA treatment and suggests that DHA may in fact be effective for a subset of patients. It also illustrates how patient-specific iPSCs can be useful for analyzing AD pathogenesis and evaluating drugs.

DOI： 10.1016/j.stem.2013.01.009

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Language：English   Publisher：The Japanese Society of Clinical Neuropsychopharmacology  

We present the case of an epileptic patient who experienced risperidone-induced hyperprolactinemia with chronic renal failure under hemodialysis. Her prolactin level was 1058 ng/ml, which was unexpectedly high. Because prolactin is mainly excreted in the urine, clinicians should pay more attention to chronic renal failure as one of the risk factors of hyperprolactinemia when prescribing risperidone.

DOI： 10.5234/cnpt.4.20

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Language：English   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Nocturnal eating/drinking syndrome is characterized by awakening in the middle of the night, getting out of bed, and consuming large quantities of food quickly and uncontrollably. We report a middle-aged male patient with schizophrenia who had nocturnal eating/drinking syndrome with restless legs syndrome whose condition improved with the administration of the herbal medicine Yi-Gan San (Yokukan-San in Japanese).

DOI： 10.1097/WNF.0b013e3182746a5b

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Publishing type：Research paper (scientific journal)  

Homoplasmic m.1624C>T mutation of the mitochondrial tRNAVal gene was previously demonstrated to cause fatal neonatal Leigh syndrome. Here, we report the clinical phenotypes of a Japanese male and his mother with heteroplasmic m.1624C>T mutation. The 36-year-old male presented with repeated episodes of consciousness disturbance since the age of 25, cognitive decline, and personality change. Cerebrospinal fluid levels of lactate and pyruvate were elevated. His mother showed similar symptoms and course. The mutation m.1624C>T was identified heteroplasmically in the proband's muscle and leukocytes and in the mother's leukocytes. The heteroplasmy load decreased with age. © 2012 Elsevier B.V. and Mitochondria Research Society.

DOI： 10.1016/j.mito.2012.10.002

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

Aims The purpose of the present study was to investigate the correlation between cognitive function and clinical variables in people with schizophrenia. Methods The subjects were 61 stabilized outpatients with schizophrenia (DSM-IV). Their mean age was 40.1 (SD?=?12.2) years. All subjects gave written informed consent to participate in the research. Cognitive function was evaluated using the Brief Assessment of Cognition in Schizophrenia. Clinical symptoms were assessed using the Positive and Negative Syndrome Scale, the Calgary Depression Scale for Schizophrenia, and the Drug-Induced Extrapyramidal Symptoms Scale. Results The Positive and Negative Syndrome Scale Negative syndrome score was significantly correlated with verbal memory score (r?=?-0.37, P?&lt;?0.01), working memory score (r?=?0.38, P?&lt;?0.01), attention and speed of information processing score (r?=?-0.51, P?&lt;?0.01), verbal fluency score (r?=?-0.39, P?&lt;?0.01), and composite score (r?=?-0.54, P?&lt;?0.01). In addition, the Drug-Induced Extrapyramidal Symptoms Scale score was significantly correlated with attention and speed of information processing (r?=?-0.45, P?&lt;?0.01), and composite score (r?=?-0.41, P?&lt;?0. 01). Dose of antipsychotics and anti-Parkinson drugs was not significantly correlated with the Brief Assessment of Cognition in Schizophrenia scores. Conclusions These results indicate that cognitive dysfunction of people with schizophrenia might be associated with negative and drug-induced extrapyramidal symptoms, suggesting that their minimization would be important for improving cognitive dysfunction.

DOI： 10.1111/j.1440-1819.2012.02390.x

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Language：Japanese   Publisher：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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Language：Japanese   Publisher：メディカルフロントインターナショナル(有)  

愛媛県東温市の幼稚園5園、小学校7校、中学校2校、高等学校1校に通う児の保護者に質問紙調査を行った。3676名から有効回答が得られた。授業中に眠くなることが週2回以上ある児の割合は、幼稚園児で1%、小学生8%、中学生21%、高校生32%であり、学齢が高いほど高率であった。授業中に居眠りしてしまうことが週2回以上ある割合は、幼稚園児1%、小学生1%、中学生6%、高校生14%であった。睡眠時間は幼稚園児が平均9時間57分、小学生が8時間28分、中学生7時間5分、高校生6時間24分であった。睡眠時間が平均より1時間以上短い群と1時間以上長い群および平均±1時間群の3群に分け、「授業中の眠気・居眠り」を群間比較したところ、小・中・高校生では睡眠時間が短いほど「授業中の眠気」が強い傾向にあったが、幼稚園児ではこの傾向は認められなかった。「授業中の居眠り」は、小・中学生では睡眠時間が短い群で有意に高頻度であったが、幼稚園児と高校生では有意な群間差は認められなかった。

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Language：Japanese   Publisher：(有)科学評論社  

愛媛県内には児童・青年期精神科専門の病棟や情緒障害児短期治療施設は存在せず、児童青年期精神医療に関する相談機関の配備にも遅れが目立つ。このような状況下で精神科医が広汎性発達障害(PDD)の診療や支援を行うにあたり、苦慮していることは想像に難くない。そこで今回、今後の支援体制を構築していく上で、まず医療機関におけるPDDの診療状況を把握することが必要と考え、県内の医療機関に従事する精神科医153名にアンケートを行った。82名から回答が得られ、次のようなことが明らかになった。1)2010年1年間に一人の医師が診療した児童青年期PDD患者数は、「10人以上」と答えた医師が7.5%、「1〜9人」が21.2%、「診療しなかった」が71.3%であった。2)2010年1年間に一人の医師が診療した成人期PDD患者数は、「10人以上」が17.5%、「1〜9人」が56.3%、「診療しなかった」が26.3%であった。3)児童青年期PDDの診療で苦慮すること(複数回答)は、「社会資源の不足」51.9%、「確定診断の困難さ」48.1%、「他機関との連携」44.4%、「親の理解」37%、「社会認識」37%などであった。4)成人期PDDの診療で苦慮することは、「確定診断の困難さ」58.7%、「発達歴の聴取」56.5%、「社会資源の不足」50%、「併存症状の存在」47.8%、「社会認識」41.3%などであった。

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Language：Japanese   Publisher：(株)医学書院  

症例1:63歳女、症例2:65歳男。2症例は、表出は少ないものの、幻覚や妄想など陽性症状の存在が疑われ、感情の平板化、活動性減退、情動的ひきこもりなどの陰性症状も強かった。コミュニケーション障害があり、感情の不安定および問題行動などから病棟での他患者との共同生活が難しく、結果として長期隔離を余儀なくされた。抗精神病薬の投与が行われたが、結果に乏しかった。Quetiapineへの置換により理学療法や作業療法などが受けられるまで陰性症状が改善した。

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2012&ichushi_jid=J00749&link_issn=&doc_id=20120814150010&doc_link_id=10.11477%2Fmf.1405102249&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1405102249&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

Genome-wide association and follow-up studies have reported an association between schizophrenia and rs12807809 of the NRGN gene on chromosome 11q24.2. We investigated the association of five linkage disequilibrium-tagging SNPs and haplotypes that cover the NRGN gene with schizophrenia in a Japanese sample of 2,019 schizophrenia patients and 2,574 controls to determine whether rs12807809 is the most strongly associated variant for schizophrenia in the vicinity of the NRGN gene. We found that the rs12807809rs12278912 haplotype of the NRGN gene was associated with schizophrenia (global P?=?0.0042). The frequencies of the TG and TA haplotypes of rs12807809rs12278912 in patients were higher (OR?=?1.14, P?=?0.0019) and lower (OR?=?0.85, P?=?0.0053), respectively, than in the controls. We did not detect any evidence of association of schizophrenia with any SNPs; however, two nominal associations of rs12278912 (OR?=?1.10, P?=?0.057) and rs2075713 (OR?=?1.10, P?=?0.057) were observed. Furthermore, we detected an association between the rs12807809rs12278912 haplotype and NRGN expression in immortalized lymphoblasts derived from 45 HapMap JPT subjects (z?=?2.69, P?=?0.007) and confirmed the association in immortalized lymphoblasts derived from 42 patients with schizophrenia and 44 healthy controls (z?=?3.09, P?=?0.002). The expression of the high-risk TG haplotype was significantly lower than the protective TA haplotype. The expression was lower in patients with schizophrenia than in controls; however, this difference was not statistically significant. This study provides further evidence of the association of the NRGN gene with schizophrenia, and our results suggest that there is a link between the TG haplotype of rs12807809rs12278912, decreased expression of NRGN and risk of developing schizophrenia. (C) 2012 Wiley Periodicals, Inc.

DOI： 10.1002/ajmg.b.32043

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Language：English   Publisher：WILEY-BLACKWELL  

Diagnosis and treatment strategies for dementia are based on the sensitive and specific detection of the incipient neuropathological characteristics, combined with emerging treatments that counteract molecular processes in its pathogenesis. Positron emission tomography (PET) is used for diverse clinical and basic studies on dementia with a wide range of radiotracers. Approaches to visualize amyloid deposition in human brains non-invasively with PET depend on imaging agents reacting with amyloid fibrils. The most widely used tracer is [11C]-6-OH-BTA-1, also known as Pittsburgh Compound-B, which has a high affinity to amyloid beta peptide (A beta) aggregates. Some 18F-labeled amyloid ligands with a longer radioactive half-life have also been developed for broader clinical applications. In addition, there have been demonstrated advantages of tracers with high specific radioactivity in the sensitive detection of amyloid, which have indicated the significance of A beta-N3-pyroglutamate as a new diagnostic and therapeutic target. Furthermore, beneficial outcomes of A beta and tau immunization in humans and mouse models have highlighted crucial roles of immunocompetent glia in the protection of neurons against amyloid toxicities. The utility of PET with a radioligand for translocator protein as a biomarker for tau-triggered toxicity, and as a complement to amyloid and tau imaging for diagnostic assessment of tauopathies with and without A beta pathologies, has also been demonstrated. Meanwhile, brain cholinergic function can be estimated by measuring acetylcholinesterase activity in the brain with PET and radiolabeled acetylcholine analogues. It has been reported that patients with early Parkinson's disease exhibit a reduction in acetylcholinesterase activity in the cerebral cortex, and this decline is more profound in patients with Parkinson's disease with dementia and dementia with Lewy bodies than in patients with Parkinson's disease without dementia. The Alzheimer's Disease Neuroimaging Initiative was a multicentre research project conducted over 6 years that studied changes in cognition, brain structure, and biomarkers in healthy elderly controls and subjects with mild cognitive impairment and Alzheimer's disease. An international workgroup of the National Institute on Aging-Alzheimer's Association has suggested that Alzheimer's disease would be optimally treated before significant cognitive impairment, defined as a presymptomatic or preclinical stage. Therefore, PET will be of technical importance for both clinical and basic research aimed at prodromal pathologies of Alzheimer's disease.

DOI： 10.1111/j.1479-8301.2012.00409.x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BIOMED CENTRAL LTD  

Background: Alzheimer's disease (AD) is the most common form of dementia. Mutations in genes such as those encoding amyloid precursor protein (APP), presenilin 1 and presenilin 2, are responsible for early-onset familial AD.
Case presentation: In this study, we report a 275341 G &gt; C (Val717Leu) mutation in the APP gene in a Japanese family with early onset AD by genetic screening. This mutation has previously been detected in European families. In the Japanese family we screened, the age at onset of AD was 47.1 +/- 3.1 years old (n = 9; range, 42-52). The symptoms in the affected members included psychiatric vulnerability and focal signs such as pyramidal signs, epileptic seizures, and myoclonic discharges. An MR imaging study showed relatively mild atrophic changes in the bilateral hippocampus and cerebral cortices in all affected members compared with their clinical presentations.
Conclusion: We conclude that the clinical features of Alzheimer's disease can be different even when caused by the same mutation in the APP gene. Further clinical and genetic studies are required to clarify the relationship between phenotypes and genotypes.

DOI： 10.1186/1471-2377-12-38

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Language：Japanese   Publisher：(株)世論時報社  

2010年に本邦で上市されたramelteonは、メラトニン受容体MT1、MT2に選択的なアゴニストであり、入眠作用や生体リズム位相変位作用を有する。現在の睡眠薬の主流はベンゾジアゼピン系睡眠薬や非ベンゾジアゼピン系睡眠薬であるが、精神疾患が基盤にある睡眠障害に対しては、抗うつ剤や抗精神病薬も治療に使用されている。このような精神疾患を伴う不眠に対し、ramelteonを使用し、30症例(男性19例、女性11例)の治療を行った。平均年齢は56.2±19.0歳(16〜89歳)であり、症例の内訳は統合失調症14例、認知症圏6例、気分障害圏4例、神経症性障害圏3例、発達障害圏3例であった。Ramelteon継続症例は22例(73.3%)であり、切り替え前後で有意に併用睡眠薬が減少した。精神疾患を伴う不眠に対するramelteonの使用は、既存の睡眠薬を減薬することができ、忍容性が高いことが示唆された。今後、精神疾患を伴う不眠へのramelteonの有効性に関して、臨床知見の蓄積が必要である。(著者抄録)

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Language：Japanese   Publisher：(公社)日本精神神経学会  

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Language：Japanese   Publisher：(公社)日本精神神経学会  

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Language：Japanese   Publisher：(一社)日本医療薬学会  

外来精神科チーム医療における患者情報の共有ツール「私のお薬連絡帳」について検討した。お薬連絡帳により収集した患者情報を基に、薬剤師が処方変更提案を行った患者は50例中29例で、総件数は47件であった。内容は、ふらつき10件、服用忘れが多いタイミングの処方9件、起床困難7件、便秘7件、薬剤性錐体外路症状6件、性機能障害5件、中途覚醒3件であった。薬剤師からの処方変更提案に対する医師の受諾率は74.5%(35件)であった。処方変更後の患者の症状は、ふらつき8件、服用忘れが多いタイミングの処方7件、起床困難5件、便秘7件、薬剤性錐体外路症状2件、性機能障害4件、中途覚醒2件で改善を認めた。お薬連絡帳を介して患者情報の提供を受けた8例の医師にアンケートを行い、すべての医師がお薬連絡帳は有用であったと答えた。また、お薬連絡帳を使用して問題発生なしとすべての医師が答えた。

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2011&ichushi_jid=J03520&link_issn=&doc_id=20111214470002&doc_link_id=%2Fdb5pharm%2F2011%2F003712%2F002%2F0675-0680%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdb5pharm%2F2011%2F003712%2F002%2F0675-0680%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：日本神経心理学会  

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Language：Japanese   Publisher：日本神経心理学会  

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Language：English   Publishing type：Research paper (scientific journal)  

We present a schizophrenic patient who experienced neuroleptic malignant syndrome with risperidone treatment due to variants of the CYP2D6 gene with reduced function. Clinicians need to be aware of this potential complication. © 2011 Elsevier Inc.

DOI： 10.1016/j.genhosppsych.2011.03.003

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Benign adult familial myoclonic epilepsy (BAFME), alternatively named familial adult myoclonic epilepsy 1/familial cortical myoclonic tremor with epilepsy 1 (FAME1/FCMTE1), is a hereditary epileptic syndrome characterized by autosomal dominant inheritance, adult-onset tremulous hand movement, myoclonus, infrequent epileptic seizure and non-progressive course without cerebellar ataxia and dementia. We previously reported evidence for linkage of BAFME to the region between D8S1784 and D8S1694 on chromosome 8q. Subsequently, other research groups reported mapping of the same clinical syndrome to different chromosomal loci, 2p and 5p, in Italian (FAME2/FCMTE2) and French (FAME3/FCMTE3) families, respectively. In this study, we performed a genome-wide linkage analysis using 10K single-nucleotide polymorphism arrays and additional microsatellite markers to reconfirm the BAFME-linked region. The BAFME-linked region was mapped to 7.16 Mb spanned by rs1898287 and rs2891799 on chromosomes 8q23.3-8q24.13 with a maximum two-point logarithm of odds score of 6.0 for the marker rs1021897. Sequence analysis and copy-number variant analysis of all 38 genes localized in the candidate region were performed, but no pathogenic mutation was identified. We conclude that the etiology of BAFME remains to be solved, and further genetic studies, which may require analysis in non-coding regions of a gene, introns or intergenic spacer regions, are necessary to reveal its unknown mutations. © 2011 The Japan Society of Human Genetics All rights reserved.

DOI： 10.1038/jhg.2011.93

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Language：Japanese   Publisher：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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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ACTA MEDICA BELGICA  

We performed an observational clinical study, the effects of tacrolimus (FK506) on the thymic output in patients with refractory inflammatory myopathies. Sixteen patients with polymyositis (PM) and 15 with dermatomyositis (DM) were treated orally with tacrolimus. Serum CK levels significantly decreased 2 to 4 months after tacrolimus therapy (p &lt; 0.01), and MRC (Medical Research Council) scores were significantly improved 2 months after tacrolimus therapy (p &lt; 0.01). T-cell receptor excision circle (TREC) content, a proxy for thymic export was not significantly different from that in age-matched controls, except for an increase in the TREC content within CD8+ single positive cells in patients with DM. TREC contents within double-positive cells and CD4(+) single-positive cells were significantly decreased 4 M after tacrolimus therapy (p &lt; 0.05) in PM/DM patients. Tacrolimus treatment significantly attenuated TREC content within cultured CD4(+)CD8(-) cells from PM/DM patients (p &lt; 0.05), but total cell counts were not significantly changed. These results indicate that tacrolimus therapy suppresses not only activated T-lymphocytes, but also some naive T-cell subsets in both PM and DM.

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Language：Japanese   Publisher：日本神経心理学会  

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Language：Japanese   Publisher：日本神経心理学会  

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Chorea-acanthocytosis (ChAc) is a rare autosomal recessive neurodegenerative disorder caused by loss of function mutations in the vacuolar protein sorting 13 homolog A (VPS13A) gene that encodes chorein. It is characterized by adult-onset chorea, peripheral acanthocytes, and neuropsychiatric symptoms. In the present study, we performed a comprehensive mutation screen, including sequencing and copy number variation (CNV) analysis, of the VPS13A gene in ChAc patients. All 73 exons and flanking regions of VPS13A were sequenced in 35 patients diagnosed with ChAc. To detect CNVs, we also performed real-time quantitative PCR and long-range PCR analyses for the VPS13A gene on patients in whom only a single heterozygous mutation was detected. We identified 36 pathogenic mutations, 20 of which were previously unreported, including two novel CNVs. In addition, we investigated the expression of chorein in 16 patients by Western blotting of erythrocyte ghosts. This demonstrated the complete absence of chorein in patients with pathogenic mutations. This comprehensive screen provides an accurate and useful method for the molecular diagnosis of ChAc. © 2011 Wiley-Liss, Inc.

DOI： 10.1002/ajmg.b.31206

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE BV  

Alterations in centrosomal function have been suggested in the pathology of schizophrenia. The molecule pericentriolar material 1 (PCM1) is involved in maintaining centrosome integrity and in the regulation of the microtubule cytoskeleton. PCM1 forms a complex at the centrosome with the disrupted-in-schizophrenia 1 (DISCI) protein, which is a major susceptibility factor for schizophrenia. The association between genetic variants in the PCM1 gene and schizophrenia has been reported by several case-control studies, linkage studies and a meta-analysis. The aims of this study are to replicate the association between four single-nucleotide polymorphisms (SNPs) in the PCM1 gene and schizophrenia in a Japanese population (1496 cases and 1845 controls) and to perform a meta-analysis of the combined sample groups (3289 cases and 3567 controls). We failed to find a significant association between SNPs or haplotypes of the PCM1 gene and schizophrenia in the Japanese population (P&gt;0.28). The meta-analysis did not reveal an association between the four examined SNPs and schizophrenia. Our data did not support genetic variants in the PCM1 gene as a susceptibility locus for schizophrenia. (C) 2011 Elsevier BM. All rights reserved.

DOI： 10.1016/j.schres.2011.03.024

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：CAMBRIDGE UNIV PRESS  

Background: Memory impairment has been proposed as the most common early sign of Alzheimer&apos;s disease (AD). The aims of this work were to evaluate the risk of progression from mild memory impairment / no dementia (MMI/ND) to clinically diagnosable AD in a community-based prospective cohort and to establish the risk factors for progression from MMI/ND to AD in the elderly.
Methods: Elderly subjects aged over 65 years were selected from the participants in the first Nakayama study. MMI/ND was defined as memory deficit on objective memory assessment, without dementia, impairment of general cognitive function, or disability in activities of daily living. A total of 104 MMI/ND subjects selected from 1242 community-dwellers were followed longitudinally for five years.
Results: During the five-year follow-up, 11 (10.6%) subjects were diagnosed with AD, five (4.8%) with vascular dementia (VaD), and six (5.8%) with dementia of other etiology. Logistic regression analysis revealed that diabetes mellitus (DM) and a family history of dementia (within third-degree relatives) were positively associated with progression to AD, while no factor was significantly associated with progression to VaD or all types of dementia.
Conclusions: DM and a family history of dementia were significant risk factors for progression from MMI/ND to clinically diagnosable AD in the elderly in a Japanese community.

DOI： 10.1017/S104161021000222X

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Language：Japanese   Publisher：(株)メディカルレビュー社  

甲状腺機能異常によって精神障害が起こることは稀ではなく、臨床上必ず検討しておくべき症状性精神障害の代表である。一般に甲状腺機能異常によって起こる精神障害は、意識障害や気分障害様の臨床症状を呈すが、橋本脳症は、甲状腺に対する自己免疫障害から起こる珍しい脳症であり、甲状腺機能異常は軽度であるにもかかわらず、痙攣、意識障害、精神病症状、認知機能障害などの精神症状および不随意運動や小脳失調などの神経症状をきたす。臨床的には、甲状腺に対する比較的高い自己免疫抗体価は示すものの、診断を確定するための典型的な所見を呈しないため、診断に難渋する事例が多く、注意が必要である。しかし、一方で、副腎皮質ステロイドや免疫抑制薬への反応は良好であるため、適切な診断と治療により、その予後を劇的に改善できることもわかっている。本稿では、橋本脳症の特徴について、精神症状に焦点を当て、自験例を交え概説したい。(著者抄録)

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Language：Japanese   Publisher：(株)世論時報社  

鏡現象とは、自己鏡像を自分ではなく、他者として誤認し、交流をもつ現象である。この現象は、アルツハイマー病(AD)に多いとされ、認知機能障害の進行に伴って出現し、さらに進行すると消失する。今回、間歇型一酸化炭素中毒後遺症にて高気圧酸素療法治療中に鏡現象が出現した初めての症例を報告する。本症例の鏡現象は、「自己鏡像に話しかける」ことが中心で、認知機能障害は重度であるなど、内容はADの報告例と一致していたが、本症例では、いったん出現した鏡現象が、認知機能の回復過程で消失し、出現パターンはADと異なっていた。本症例では、脳血流シンチグラフィーにおいて、両側前頭葉から側頭頭頂葉における血流低下を認めたが、鏡現象を大脳巣症状として捉えることは困難であった。今後は、鏡現象における神経基盤の解明のため、詳細な臨床観察や神経画像など包括的な研究が必要と思われる。(著者抄録)

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Language：Japanese   Publisher：(公社)日本精神神経学会  

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It has been suggested that mitochondrial dysfunction is important in the pathogenesis of psychiatric disorders such as depression, schizophrenia and dementia. We report herein three adult patients exhibiting such psychiatric symptoms as the core manifestation, accompanied by various degrees of myopathic symptoms. Pathological findings in biopsied skeletal muscle were compatible with mitochondrial myopathy in all cases. Maternal inheritance was not apparent in all three cases; however, two patients were born to consanguineous parents. Mutation analysis on the mitochondrial DNA (mtDNA) and seven nuclear genes, in which pathogenic mutations are known to cause mtDNA deletions, was performed. MtDNA deletion mutations were identified in skeletal muscles of all patients. Neither pathogenic mutations nor copy number variation was identified among the nuclear genes. Although further studies are needed, the molecular pathways inducing mitochondrial abnormalities may be implicated in a variety of psychiatric conditions. © 2010 Elsevier Ireland Ltd and the Japan Neuroscience Society.

DOI： 10.1016/j.neures.2010.12.013

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

Background:
Semantic dementia (SD) has been recognized as a representative of dementia with presenile onset; however, recent epidemiological studies have shown that SD also occurs in the elderly. There have been few studies about the differences of clinical profiles between early-onset SD (EO-SD) and late-onset SD (LO-SD). Age-associated changes in the brain might cause some additional cognitive and behavioural profiles of LO-SD in contrast to the typical EO-SD cases. The aim of the present study was to clarify the characteristics of neuropsychological, and behavioural and psychological symptoms of dementia (BPSD) profiles of LO-SD patients observed in screening tests in comparison with EO-SD patients and late-onset Alzheimer&apos;s disease (LO-AD) patients as controls.
Methods:
Study participants were LO-SD (n = 10), EO-SD (n = 15) and LO-AD (n = 47). We examined the Mini-Mental State Examination (MMSE), the Raven&apos;s Coloured Progressive Matrices (RCPM), the Short-Memory Questionnaire (SMQ), the Neuropsychiatric Inventory (NPI) and the Stereotypy Rating Inventory (SRI).
Results:
Both SD groups scored significantly lower than the LO-AD patients in &apos;naming&apos; of the MMSE. In the &apos;construction&apos; score of the MMSE and the RCPM score, however, the LO-SD patients as well as the LO-AD patients were significantly lower than the EO-SD patients. In the SMQ score, &apos;euphoria&apos; and &apos;disinhibition&apos; scores of the NPI, the SRI total and subscale scores, both SD groups were significantly higher, whereas in the &apos;delusion&apos; score of the NPI, both SD groups were significantly lower than the LO-AD patients.
Conclusions:
Visuospatial and constructive skills of LO-SD patients might be mildly deteriorated compared with EO-SD patients, whereas other cognitive and behavioural profiles of LO-SD are similar to EO-SD. Age-associated changes in the brain should be considered when we diagnose SD in elderly patients.

DOI： 10.1111/j.1479-8301.2010.00351.x

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Neuroacanthocytosis syndromes are mainly comprised of two diseases: chorea-acanthocytosis (ChAc) and McLeod syndrome (MLS). There is a high incidence of psychiatric disorders such as mood disorder and schizophrenia among neuroacanthocytosis patients. We hypothesized that neuroacanthocytosis-related-genes might be associated with susceptibility to these psychiatric disorders. We performed a comprehensive mutation screen of VPS13A and XK, the gene responsible for ChAc and MLS, respectively, in 85 mood disorder subjects and XK in 86 schizophrenia subjects and compared the variants to 100 or more control alleles. We also performed copy number variation (CNV) analysis in 72 mood disorder subjects and 86 schizophrenia subjects. We identified three non-synonymous, two synonymous and six intron variants in mood disorder subjects and a novel GAT triplet repeat polymorphism in VPS13A. By CNV analysis, we identified a heterozygous exon 60-61 deletion in VPS13A in one mood disorder subject. We identified one non-synonymous and one intron variant in mood disorder and schizophrenia subjects, respectively, in XK. The presence of a pathogenic mutation or a potentially functional variant in mood disorder or schizophrenia subjects suggests that neuroacanthocytosis-related-genes might be involved in the pathogenesis of these psychiatric disorders. © 2010 Elsevier Ireland Ltd and the Japan Neuroscience Society.

DOI： 10.1016/j.neures.2010.12.001

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

The atypical antidepressant, mirtazapine enhances noradrenergic transmission, but its effects on serotonergic transmission remain to be clarified. The present study determined the effects of acute and chronic administration of mirtazapine on serotonergic transmissions in raphe nuclei and their innervation regions, frontal and entorhinal cortex, using multiple-probes microdialysis with real-time PCR and western blotting. Acute administration of mirtazapine did not affect extracellular serotonin level in raphe nuclei or cortex; however, chronic administration increased extracellular serotonin level in raphe nuclei without affecting that in cortex. Blockade of 5-HT1A receptor, but not that of the 5-HT2A/2C receptor, enhanced the effects of acute administration of mirtazapine on extracellular serotonin level in raphe nuclei. Chronic mirtazapine administration reduced the inhibitory function associated with somatodendritic 5-HT1A receptor in raphe nuclei, but enhanced postsynaptic 5-HT1A receptor in serotonergic innervated cortical regions. Chronic administration reduced the expression of mRNA and protein of serotonin transporter and 5-HT1A receptor in raphe nuclei, but not in the cortices. These results suggested that acute administration of mirtazapine probably activated serotonergic transmission, but its stimulatory action was abolished by activated inhibitory 5-HT1A receptor. Chronic administration of mirtazapine resulted in increased extracellular serotonin level via reduction of serotonin transporter with reduction of somatodendritic 5-HT1A autoreceptor function in raphe nuclei. These pharmacological actions of mirtazapine include its serotonergic profiles as noradrenergic and specific serotonergic antidepressant (NaSSA). (C) 2011 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.neuropharm.2010.12.025

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：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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Language：English   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

The main purpose of the present study was to examine the relationship between quality of life (QOL) and cognitive dysfunction in schizophrenia. Subjects were 61 stabilized outpatients. Quality of life and cognitive function were assessed using the Quality of Life Scale (QLS) and the Brief Assessment of Cognition in Schizophrenia (BACS), respectively. Clinical symptoms were evaluated with the Positive and Negative Syndrome Scale (PANSS) and the Calgary Depression Scale for Schizophrenia (CDSS). The BACS composite score and the BACS Verbal memory score were positively correlated with the QLS total score and two subscales. The BACS Attention and speed of information processing score had positive correlation with the QLS total and all the subscales scores. The PANSS Positive and Negative syndrome scores also had significant correlations with the QLS total score and all of the subscales. In addition, the CDSS score was negatively correlated with the QLS total score and some of the subscales. Stepwise regression analysis showed that the BACS Attention and speed of information processing score was an independent predictor of the QLS total score but it was less associated with the QLS than the PANSS Negative syndrome score and the CDSS score. The results suggest that negative and depressive symptoms are important factors on patients' QOL and also support the view that cognitive performance provides a determinant of QOL in patients with schizophrenia. (C) 2010 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.pnpbp.2010.08.018

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Language：Japanese   Publisher：(有)科学評論社  

過去に統合失調症と診断され、精神運動興奮状態のため入院に至ったが、入院中の詳細な生育歴の聴取や入院中の行動観察、および薬物反応よりアスペルガー障害と診断を改め、支援および治療を再検討することにより軽快した2症例(25歳男性、24歳女性)について報告した。本2例は家庭内不適応で入院に至ったが、入院治療中の目的を明確にし、退院後の方向性を入院中に決めておくことや退院後の生活の基盤となる家族への疾患教育が必須であると示唆された。

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：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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Language：Japanese   Publisher：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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Language：Japanese   Publisher：(公社)日本精神神経学会  

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Language：Japanese   Publisher：日本神経心理学会  

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Language：Japanese   Publisher：(株)ワールドプランニング  

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Language：Japanese   Publisher：(株)星和書店  

トゥレット障害の主な薬物療法は、haloperidolやpimozide、risperidoneなどの抗精神病薬が使用されるが、近年、トゥレット障害に対するaripiprazoleの使用についての報告が散見される。AripiprazoleはドーパミンD2受容体部分アゴニストであり、多くの抗精神病薬がドーパミンD2受容体アンタゴニストであることから、特殊な薬理学特性を持つ抗精神病薬と言える。Aripiprazoleは、また、強力な抗精神病作用を有し、錐体外路症状、代謝異常や過鎮静をきたしにくい安全性の高い抗精神病薬のため、統合失調症の第一選択薬として国内で認識され、広く使われている。今回、我々は、トゥレット障害と診断し、多彩なチック症状に対してaripiprazoleの使用により改善に至った2症例を経験したので報告する。1例目は14歳男性、risperidoneによる治療を開始したが、過鎮静と効果不十分のためaripiprazoleに置換して6mg/日から開始、24mg/日まで増量し、奏効した。2例目は12歳男性、広汎性発達障害が併存していた。Aripiprazole 3mg/日から開始し、12mg/日まで増量したところ、チック症状は改善した。2症例とも副作用は眠気のみであった。以上から、aripiprazoleは、継続投与が可能で忍容性が高く、効果が期待でき、トゥレット障害に用いることのできる薬物治療の選択肢の1つであると判断した。(著者抄録)

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Language：Japanese   Publisher：(株)星和書店  

児童青年期双極性障害における睡眠障害は、躁病エピソード・うつ病エピソードいずれにも関連する臨床症状として重要な所見である。睡眠の質・量の低下や睡眠覚醒リズムの問題は、日中の活動性・認知面・学習面への影響が大きく、特に児童期において発達に及ぼす影響を考慮すると、早期発見・早期介入が必要である。児童青年期における睡眠障害の薬物療法については、十分なコンセンサスが得られておらず、心理学的介入や認知行動療法が主として用いられる。認知行動療法的アプローチをする上で、夜間の睡眠状態に加えて日中の活動性も把握できる睡眠日誌は有用である。(著者抄録)

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Language：Japanese   Publisher：(公社)日本精神神経学会  

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Language：Japanese   Publisher：(株)医学書院  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2010&ichushi_jid=J00749&link_issn=&doc_id=20100527180009&doc_link_id=10.11477%2Fmf.1405101629&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1405101629&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

Language：English   Publishing type：Research paper (scientific journal)   Publisher：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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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE BV  

The chitinase 3-like 1 (CHI3L1) gene acts as a cellular survival factor in response to several environmental and psychosocial stresses. The expression level of CHI3L1 was increased in the hippocampus and prefrontal cortex regions of patients with schizophrenia. Genetic variants of the CHI3L1 gene have been significantly associated with schizophrenia in two distinct ethnic groups, the Chinese and Irish populations. The aims of this study are to confirm the association between the CHI3L1 gene and schizophrenia in a Japanese population using the largest sample size to date (1463 cases and 1795 controls) and perform a meta-analysis of the combined samples (3005 cases, 3825 controls and 601 trios). We found significant associations between single nucleotide polymorphism (SNP) 4/rs4950928 (p = 0.009), which is located in the promoter region of the CHI3L1 gene, and haplotypes including this SNP and schizophrenia (the most significant global p&lt;0.001). As the meta-analysis of the combined samples showed significant heterogeneity among studies of SNP3/rs10399805 (p = 0.026) and SNP4 (p&lt;0.001), we performed meta-analyses separately in the Japanese (2033 cases and 2365 controls) and Chinese populations (412 cases, 464 controls and 601 trios), the major groups analyzed in association studies of the CHI3L1 gene. The meta-analysis in Japanese populations showed stronger evidence for the association of schizophrenia with SNP4 (p = 0.003), while the meta-analysis in Chinese populations showed an association with a different variant (SNP3) (p = 0.003). We conclude that the genetic variants in the CHI3L1 gene have ethnic heterogeneity and confer a susceptibility to schizophrenia in Asian populations. (C) 2009 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.schres.2009.12.002

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：KARGER  

Background/Aims: The aim of this study is to examine the clinical symptoms in a number of semantic dementia (SD) patients and to reveal the longitudinal progression and clinical course of these distinctive symptoms of SD. Methods: 19 consecutive SD patients were examined. Symptoms were classified into 23 distinct categories: behavioral symptoms, language and cognitive symptoms and symptoms concerning the impairment of activities of daily living (ADL). We divided patients into two subgroups, left-and right-dominant SD, and compared the onset of each symptom. Results: Language impairments occurred as the initial symptom in 16 cases. At the first examination, all cases showed both anomia and impairment of word comprehension. By around 3 years after onset, almost all language impairments were observed. Approximately 3-5 years after onset, prosopagnosia and behavioral symptoms appeared. Around the period when the loss of the language faculty and apathy became remarkable, impairment of ADL appeared. Patients spent all day in bed at this stage. Moreover, prosopagnosia appeared significantly earlier in right-dominant SD. Conclusion: Our findings clarify the progression of distinctive symptoms of SD patients. It is necessary to create a treatment strategy for SD patients with such a disease-specific course of SD. Copyright (C) 2010 S. Karger AG, Basel

DOI： 10.1159/000269972

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Language：Japanese   Publisher：日本神経心理学会  

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Language：Japanese   Publisher：日本神経心理学会  

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Language：Japanese   Publisher：(株)ライフ・サイエンス  

子どもの睡眠の問題を調査・スクリーニングする手法としては、問診票を用いた調査が最も簡便であるが、特に子どもの調査においては、年齢とともに睡眠の量的・質的変化がみられることに加え、睡眠環境の影響も受けることから、問診項目や設問の内容に工夫が必要である。われわれは幼児〜高校生までの幅広い年齢層に対応し、医療・教育・公衆衛生の分野で睡眠の問題をスクリーニングすることを目的として、「児童青年期睡眠チェックリスト(CASC)」を作成し、これを用いた睡眠調査・問診システムを構築した。CASCの特徴は、同一の設問セットで横断的なスクリーニングと、経時的追跡を行えることに加え、年齢に応じて保護者記入版、本人記入版を併用することで、より幅広く正確な情報を得ることができる点である。今後、各年代の標準化を行い、疫学調査や小児睡眠臨床において活用することで、小児の睡眠問題のマネジメントに貢献する有力なツールとなることが期待される。(著者抄録)

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2009&ichushi_jid=J04991&link_issn=&doc_id=20090812050014&doc_link_id=%2Fai5slepd%2F2009%2F000303%2F015%2F0404-0408%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fai5slepd%2F2009%2F000303%2F015%2F0404-0408%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

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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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Language：English   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

DOI： 10.1097/YPG.0b013e32832a5030

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Language：Japanese   Publisher：(公社)日本精神神経学会  

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Language：Japanese   Publisher：(公社)日本精神神経学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：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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Language：Japanese   Publisher：(公社)日本精神神経学会  

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Language：Japanese   Publisher：(公社)日本精神神経学会  

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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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Language：English   Publishing type：Research paper (scientific journal)   Publisher：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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Language：English   Publishing type：Research paper (scientific journal)   Publisher：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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© 2008 Springer-Verlag Berlin Heidelberg. All rights are reserved. We have recently generated a model mouse of chorea-acanthocytosis (ChAc), which carries a targeted deletion mutation in the mouse VPS13A gene corresponding to a human disease mutation. Although these model mice exhibited a normal life span, they begin to display a disease phenotype with red cell acanthocytosis and behavioral abnormalities in old age. Neuropathological examination reveals prominent apoptotic neuronal cells and astrogliosis in the striatum. These are thought to be very similar to the features of the disease course and neuropathology seen in ChAc patients. Thus, this model mouse may be useful for pathogenic studies related to ChAc. Here, we review the ChAc-model mouse and recent findings on the upregulation of gephyrin and its related proteins in ChAcmodel mouse striatum.

DOI： 10.1007/978-3-540-71693-8_12

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DOI： 10.1002/mds.21556

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Language：Japanese   Publisher：一般社団法人 日本心身医学会  

DOI： 10.15064/jjpm.47.12_1053_2

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Publisher：9  

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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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Language：English   Publisher：ELSEVIER SCIENCE INC  

DOI： 10.1016/j.genhosppsych.2005.09.003

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Language：Japanese   Publisher：(公財)先進医薬研究振興財団  

有棘赤血球舞踏病(ChAc)発症者およびその家族について有棘赤血球舞踏病原因遺伝子CHAC(VPS13A)の変異を検索し,精神神経障害の多因子性を検討した.ChAc発症者40例を含む30家系68例を対象とした.未報告の疾患変異9種を同定した.発症者40例中,疾患変異をホモ接合性もしくは複合ヘテロ接合性に有すものは16例で,一つの疾患変異をヘテロ接合性に有すのみのものが8例あった.残りの16例の発症者は疾患変異を認めなかった.疾患変異を1箇所ヘテロ接合性に有すのみでありながらChAcの臨床症状を呈す症例が存在することから,ChAcの遺伝形式が浸透率の低い優性遺伝である可能性および発症に関与するその他の修飾因子の存在が推測された

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Language：English   Publishing type：Research paper (international conference proceedings)  

To investigate the brain activation in the prefrontal cortex (PFC) during mental works, we examined blood oxygenation changes of healthy subjects by using multi channel near infrared spectropcopy (NIRS). It was directly confirmed that the PFC was activated during mental tasks in vivo and it was suggested that distribution of the activation in the PFC is different among healthy individuals.

DOI： 10.2152/jmi.52.302

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Language：English   Publishing type：Research paper (international conference proceedings)  

Precise assessment of stress is an imminent issue to deal with stress-related social, medical and psychological problems. Psychological stress is known to stimulate the neuroendocrine, sympathetic nervous, and immune systems. By analyzing mRNA expression levels in leukocytes, which express receptors for hormones, neurotransmitters, growth factors, cytokines, and other stress related signals, levels of stress may be adequately measured. In a series of studies, our group has developed a cDNA microarray specifically designed to measure the mRNA levels of stress-related genes in peripheral blood leukocytes. This microarray enabled us to sensitively detect the response to psychological stress. In addition, our preliminary study suggests that the array could differentiate patients with depression from sex- and age-matched control subjects.

DOI： 10.2152/jmi.52.266

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Language：English   Publisher：ELSEVIER SCIENCE INC  

DOI： 10.1016/j.genhosppsych.2005.02.003

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Publishing type：Part of collection (book)  

© 2004 Springer. All Rights Reserved. Chorea-acanthocytosis (ChAc) is a hereditary neurodegenerative disease showing Huntington disease-like neuropsychiatric symptoms and peripheral blood red cell acanthocytosis. Recently, we have identified the gene, CHAC, encoding a newly discovered protein, chorein, in which a deletion mutation was found in three Japanese ChAc families. Although four patients possessed the same mutation homozygously, their clinical characteristics varied, which means that multifactorial effects on the pathogenesis are present. Even some of the heterozygous carriers in the families showed a slight degree of acanthocytosis and psychiatric features including emotional lability or cognitive disturbance. We found heterozygous carriers of the deletion-mutation allele in the group of patients with mood disorder. The CHAC gene product, chorein, may function as an important protein in the brain not only for motor but also for mental function.

DOI： 10.1007/1-4020-2898-9_5

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Language：Japanese   Publisher：(公財)先進医薬研究振興財団  

今回,日本人家系で見つかった有棘赤血球舞踏病(CHAC)の病因となる愛媛欠失変異を持ったモデルマウスを作成し,その表現型の解析を行った.モデルマウスでは,老齢化後に運動機能障害と末梢血有棘赤血球症を認め,浸透圧試験で赤血球の脆弱性が実証された.行動解析でCHACモデルマウスでは自発運動量が減少し,ソーシャルインタラクションは有意に減少した.病理学的所見では線条体でアポトーシスとグリオーシスが存在し,抗GAD抗体陽性神経細胞と線維,抗TH抗体陽性神経線維が減少した.黒質ではpars reticulataにグリオーシスが見られ,抗GAD抗体陽性神経細胞と線維,抗TH抗体陽性神経線維の抗サブスタンスP抗体陽性線維の減少をもたらした.これらの所見はヒトでの所見と合致し,作成したマウスはCHACの疾患モデルとして妥当であると考えられた

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Language：Japanese   Publishing type：Research paper (scientific journal)  

We report a 71-year-old woman showing rapidly progressive non-fluent aphasia and dementia accompanied by motor neuron disease (MND). There was no family history of dementia or motor neuron disease. There was 10 months history of dysarthria and dysphagia. On examination, she showed profound difficulty in articulation. Her comprehension was impaired in that she was unable to obey three-stage command. Her written language was also impaired with phonological spelling errors, syntactic errors, and perseveration. Neuroradiological investigations showed atrophic changes and hypoperfusion of left temporal and bilateral parietal region revealed by MRI and SPECT, respectively. Her subsequent decline was rapid. It might be likely that aphasia is much more common in dementia with bulbar MND than is currently recognized because bulbar palsy might mask the language disorder.

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Language：Japanese   Publisher：(株)医学書院  

71歳女.構音障害,嚥下障害等,球麻痺症状で発症し,失語が前景に立った痴呆症状が出現し,急速に進行して失外套症候群に至った.痴呆や運動ニューロン疾患の家族歴はなかった.運動ニューロン疾患を伴う痴呆症や前頭側頭型痴呆とは異なり,人格変化等の前頭葉症状は目立たないこと,非流暢性失語が前景に出た痴呆症状がみられたこと,形態画像で左側頭葉と両側頭頂葉の障害がみられたことから,非典型的であった

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2002&ichushi_jid=J01231&link_issn=&doc_id=20020918160011&doc_link_id=10.11477%2Fmf.1406901991&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1406901991&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

Publishing type：Research paper (scientific journal)  

Enhancer/silencer activity of each allelic variant of the human serotonin transporter linked polymorphic region (5-HTTLPR) including newly found ones was measured in several cell lines including raphe-nucleus-derived RN46A. 5-HTTLR variants ligated in pGL-3 promoter vector increased luciferase activity in COS-7 cells and PC12 cells, where no significant differences among the variants were observed. In RN46 cell lines, however, 5-HTTLPRs decreased luciferase activity to 80-30%, acting as silencers not as enhancers. Some allelic variants (15, 19, 20 and 22) showed even significantly stronger silencer activities than others in RN46A. We also examined relationship between allelic frequencies, the enhancer/silencer activities and incidents of mood disorder. The categorized genotypic or allelic frequencies was not significantly different between the mood disorder and the control. No significant difference was detected either when analyzed by silencer activities of each allelic variant. © 2002 Elsevier Science Ireland Ltd. All rights reserved.

DOI： 10.1016/S0304-3940(02)00348-8

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Language：English   Publishing type：Research paper (scientific journal)  

Abstract: Viral T antigens are transcription factors that have been suspected of inhibiting expression of the myelin basic protein (MBP) mRNA at the translational level in vitro and in vivo. The effect of simian virus 40 (SV40) large T antigen (T‐ag) was examined on the translation of the 14‐kDa MBP mRNA in reticulocyte lysates and on MBP expression after transfection into cells that express SV40 T‐ag. SV40 T‐ag did not inhibit translation of 14‐kDa MBP cRNAs in cell‐free translations even at 30 µM (∼600 µg/ml) T‐ag. Permanent transfection of COS‐1 cells (which endogenously express SV40 T‐ag) with the 14‐kDa MBP cDNA resulted in the expression of the 14‐kDa MBP as determined by western blot analysis. Permanent transfection of N20.1 cells, an oligodendrocyte line immortalized with a temperature‐sensitive SV40 T‐ag, with the 14‐kDa MBP cDNA construct also resulted in the expression of the 14‐kDa MBP under conditions in which the cells expressed functional SV40 T‐ag. These results indicate that SV40 T‐ag does not prevent expression of the MBP gene at the translational level and that in those immortalized oligodendrocyte lines that express MBP mRNA, but not MBP protein, some factor other than the SV40 large T‐ag is responsible for the posttranscriptional regulation. Copyright © 1995, Wiley Blackwell. All rights reserved

DOI： 10.1046/j.1471-4159.1995.64020928.x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT-RAVEN PUBL  

A sensitive and specific method for determining three forms of methylarginine, i.e., N(G)-monomethylarginine, N(G),N(G)-dimethylarginine, and N(G),N'G-dimethylarginine, in mammalian tissues was developed. After partial purification by ion-exchange chromatography, the methylarginines were derivatized to phenylthiocarbamyl compounds and quantitatively determined using HPLC with a reverse-phase C18 column. In rat organs, the highest concentrations of methylarginines were observed in the spleen. In rat brain, cerebellum and olfactory bulb contained large amounts of N(G)-monomethylarginine and N(G),N(G)-dimethylarginine. A detailed study of the distribution of methylarginines in the bovine brain was also made, and the concentration of N(G),N'G-dimethylarginine was almost the same in all regions. The cerebellar gray matter, hippocampus, and hypothalamus contained large amounts of methlarginines. The distribution of methylarginines seems to parallel the distribution of nitric oxide synthase, which is known to be inhibited by N(G)-monomethylarginine. This may indicate that methylarginines play some role in controlling nitric oxide synthase activity.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT-RAVEN PUBL  

Methylarginines in free form were identified in bovine brain. Three compounds were isolated from the basic aliphatic amino acid fraction of bovine brain with several ion-exchange chromatographies. They showed the same R(f) values in paper and thin-layer chromatographies as those of authentic N(G)-monomethylarginine, N(G),N(G)-dimethylarginine, and N(G),N'(G)-dimethylarginine. The migration distance of the isolated compounds in high-voltage paper electrophoresis and the retention times in ion-exchange HPLC were also identical to those of the above authentic methylarginines. We concluded that these three compounds are the methyl derivatives of arginine described above. The amount of these three compounds isolated from 1,090 g of bovine brain was 0.3-mu-mol of N(G)-monomethylarginine, 0.1-mu-mol of N(G),N(G)-dimethylarginine, and 0.5-mu-mol of N(G),N'(G)-dimethylarginine. The occurrence of these free methylarginines may have an important role in regulating the signal transduction through the nitric oxide system.

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Language：Japanese   Publisher：The Japan Endocrine Society  

To clarify the role of the sympatho-adrenomedullary and renin-angiotensin-aldosterone systems, and catecholamine receptors, in the pathogenesis of orthostatic hypotension in diabetes mellitus (DM), urinary excretion of catecholamines, and plasma levels of norepinephrine (PNE), epinephrine (PE), renin activity (PRA), aldosterone (PAC), cyclic AMP (PcAMP) and cyclic GMP (PcGMP) were measured in 16 normal subjects (N) and 50 diabetic patients with or without orthostatic hypotension (DMOH (+), DMOH (-)). Changes in PNE, PE, PRA, PAC, PcAMP and PcGMP by standing, glucagon (G) adminsitration and cold pressor test were examined. Furthermore, the effect of metoclopramide on catecholamine levels and blood pressure was investigated before and after cold pressor test. The results were following;<BR>(1) Urinary free norepinephrine excretion was significantly lower in DMOH (+), while urinary total norepinephrine excretion was normal in the two DM groups. Urinary free and total epinephrine excretions were lower in DMOH (+) than in N and DMOH (-).<BR>(2) PNE and PE were elevated after standing in all groups tested, and more pronounced in some cases of DMOH (+). Although PRA and PAC were elevated normally after standing in all groups, a dissociation between the two parameters was seen in some cases of DM. PcAMP after standing was correlated with PE (r=0.829). Basal PcGMP was high in manycases of DMOH (+). However, no difference in the elevation of PcGMP after standing was noted between N and the two DM groups.<BR>(3) Systolic blood pressure (SBP) rose markedly in only DMOH (+) from 146 ± 27mmHg to 178 ± 34mmHg 5 minutes after G administration. The increment of PNE and PE 5 minutes after G administration were similar in all groups. In only DMOH (+), the increase in PcAMP 15 minutes after G test was proportional (r=0.498) to that of epinephrine.<BR>(4) Responses of SBP, PNE, PE and PAC to cold pressor test apparently improved after administration of metoclopramide (MC) in some patients with DM.<BR>These results suggest that not only organic disturbance of sympathetic nerves but also functional inhibition of norepinephrine release mediated by dopamine receptor, may play an important role in the pathogenesis of orthostatic hypotension in diabetes mellitus. It is considered that catecholamine secretion from the adrenal medulla in DMOH (+) is increased by hypotension induced by standing. Furthermore, the vascular response to catecholamines may be accelerated through the increment of the extrajunctional receptor in DMOH (+).<BR>In conclusion, for the purpose of finding any abnormality in blood pressure regulation in the early stages of diabetes mellitus, it is necessary to clarify the sympathetic and dopamine activities by orthostatic, glucagon loading and cold pressor tests. Therefore, it is suggested that sympathetic stimulants are useful for patients with sympathetic dysfunction; and antidopaminergic drugs for those diabetic patients with the hyperdopaminergic state.

DOI： 10.1507/endocrine1927.64.12_1293

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Other Link： http://search.jamas.or.jp/link/ui/1990046456

Language：Japanese  

CiNii Books

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Language：Japanese   Publisher：メディカルレビュー社  

CiNii Books

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J-GLOBAL

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Language：Japanese   Publisher：先端医学社  

CiNii Books

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Language：Japanese   Publisher：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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Language：Japanese   Publisher：(一社)日本認知症学会  

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Language：Japanese   Publisher：(一社)日本関節病学会  

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Language：Japanese   Publisher：医歯薬出版(株)  

健康寿命を伸ばすためには身体的活動を保つことが重要であり、そのためには身体的な視点に加え精神・心理的な視点を持たなければならない。高齢者では、加齢により、生物・心理・社会的にすべての能力が低下することから、自己肯定感を損ねがちで、それがさらに閉じこもりを引き起こすという悪循環を導く可能性もある。高齢者に起こる身体的活動が低下する精神疾患の代表であるうつ病は、うつ症状に加え、不定愁訴が多いこと、認知症と間違えられる認知機能低下がみられること、加えて自殺率が高いことから、早期に診断し適切な治療的介入を行わなければいけない病気である。高齢者のうつ病の治療においても、若年者と同様に安静・休養は大事であるが、早期に改善させることにより身体不活動をできるだけ予防すべきで、高齢とはいえ抗うつ薬は副作用に留意しつつも十分量・十分期間使わなければならない。施行できる機関は限られるが、電気痙攣療法も有効な治療法のひとつである。そして、精神療法においては、常に礼節を持って接し、若年者以上に自己肯定感を高めるようにしなければならない。(著者抄録)

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J00060&link_issn=&doc_id=20190722030012&doc_link_id=%2Faa7ayuma%2F2019%2F027003%2F013%2F0273-0278%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Faa7ayuma%2F2019%2F027003%2F013%2F0273-0278%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：(株)ワールドプランニング  

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Language：Japanese   Publisher：(株)ワールドプランニング  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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J-GLOBAL

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Language：Japanese   Publisher：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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Language：Japanese   Publisher：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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Language：Japanese   Publisher：(株)中外医学社  

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Language：Japanese   Publisher：(株)中外医学社  

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Language：Japanese   Publisher：(公社)日本精神神経学会  

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Language：Japanese   Publisher：(公社)日本精神神経学会  

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Language：Japanese   Publisher：(公社)日本精神神経学会  

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Language：Japanese   Publisher：(公社)日本精神神経学会  

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Language：Japanese   Publisher：(公社)日本精神神経学会  

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Language：Japanese   Publisher：(公社)日本精神神経学会  

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Language：Japanese   Publisher：愛媛医学会  

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Language：Japanese   Publisher：(一社)日本認知症学会  

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Language：Japanese   Publisher：(一社)日本認知症学会  

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Language：Japanese   Publisher：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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Language：Japanese   Publisher：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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Language：Japanese   Publisher：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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Language：Japanese   Publisher：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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Language：Japanese   Publisher：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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Language：Japanese   Publisher：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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Language：Japanese   Publisher：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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Language：Japanese   Publisher：(公社)日本精神神経学会  

J-GLOBAL

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Language：Japanese   Publisher：(公社)日本精神神経学会  

J-GLOBAL

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Language：Japanese   Publisher：(公社)日本精神神経学会  

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Language：Japanese   Publisher：(公社)日本精神神経学会  

J-GLOBAL

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Language：Japanese   Publisher：(株)星和書店  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J03168&link_issn=&doc_id=20170424290013&doc_link_id=issn%3D1343-3474%26volume%3D20%26issue%3D5%26spage%3D585&url=http%3A%2F%2Fwww.pieronline.jp%2Fopenurl%3Fissn%3D1343-3474%26volume%3D20%26issue%3D5%26spage%3D585&type=PierOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00005_2.gif

Language：Japanese   Publisher：多文化間精神医学会  

J-GLOBAL

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Language：Japanese   Publisher：(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)

J-GLOBAL

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Language：Japanese   Publisher：(一社)日本認知・行動療法学会  

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Language：Japanese  

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Other Link： http://search.jamas.or.jp/link/ui/2016374386

Language：Japanese   Publisher：(一社)日本神経精神薬理学会  

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Language：Japanese  

CiNii Books

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Other Link： http://search.jamas.or.jp/link/ui/2016356351

Language：Japanese   Publisher：(公社)日本精神神経学会  

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Language：Japanese  

CiNii Books

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Other Link： http://search.jamas.or.jp/link/ui/2016057131

Language：Japanese   Publisher：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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Language：Japanese   Publisher：(一社)日本神経治療学会  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：CAMBRIDGE UNIV PRESS