記述言語：日本語   出版者・発行元：Translational Psychiatry  

Tardive dyskinesia (TD) is a severe condition characterized by repetitive involuntary movement of orofacial regions and extremities. Patients treated with antipsychotics typically present with TD symptomatology. Here, we conducted the largest GWAS of TD to date, by meta-analyzing samples of East-Asian, European, and African American ancestry, followed by analyses of biological pathways and polygenic risk with related phenotypes. We identified a novel locus and three suggestive loci, implicating immune-related pathways. Through integrating trans-ethnic fine mapping, we identified putative credible causal variants for three of the loci. Post-hoc analysis revealed that SNPs harbored in TNFRSF1B and CALCOCO1 independently conferred three-fold increase in TD risk, beyond clinical risk factors like Age of onset and Duration of illness to schizophrenia. Further work is necessary to replicate loci that are reported in the study and evaluate the polygenic architecture underlying TD.

DOI： 10.1038/s41398-021-01471-y

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記述言語：日本語  

DOI： 10.1016/j.isci.2021.102145

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記述言語：日本語   出版者・発行元：International Medical Journal  

Objective: The aim of this study was to investigate whether a teacher's language choice in task-based English communicative classes could affect students' enjoyment, anxiety, and English proficiency improvement. Design: Two groups: English-only (EE group) and with some legitimate Japanese support (EJ group) were created and their enjoyment, anxiety and English proficiency improvement were compared. Methods: The questionnaire ninety-two students took twice (at the entry and at the end) was used to measure the levels of students enjoyment and anxiety. The change between the term tests' scores was used to measure the levels of students' English proficiency improvement. Results: The levels of enjoyment significantly increased in the EE group, and each student's score from the midterm to the final exam significantly increased in the EJ group. Conclusion: Japanese support instruction might contribute to English proficiency improvement of basic to low intermedi-ate-level students.

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CiNii Research

記述言語：日本語   出版者・発行元：Proceedings of SPIE - The International Society for Optical Engineering  

CTA (Cherenkov Telescope Array) is a project for the next generation of the ground-based gamma-ray observatory. CTA will cover a wide energy range, 20 GeV and 300 TeV, by 3 types of the telescopes whose diameters are different. The Large-Sized Telescopes (LSTs) of the CTA are designed to cover the lowest energy range. We are working on mirrors for 4 LSTs which will be built at La Palma, Spain. The parabolic primary mirror of CTA-LST is 23 m diameter and its focal length is 28 m. The primary mirror consists of 198 segmented mirrors. Total effective reflective area is about 370 m2. Each mirror has a hexagonal shape of 1.51 m side-by-side size. It has a sandwich structure which consists of aluminum honeycomb (60 mm thickness) and two glass surfaces (2.7 mm) and the total weight is about 47 kg. We used a sputtering deposition technique to coat in the surface with 5 layer. The coated layers protect the surface for long operation such as 10 years at outside with a reflectance degradation of less than 1 % a year. The reflectance of the mirror reaches about 92 % at 400 nm and its resolution is 0.5 mrad in diameter that contains the 80 % light reflected by the mirror. The production technique based on cold slumping gave us the stable its production. We report on the design of the segment mirror and the production of about 950 hexagonal 2 m2 mirrors to achieve the parabolic shape of the optical system for 4 LSTs.

DOI： 10.1117/12.2562111

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記述言語：日本語   出版者・発行元：International Medical Journal  

Objective: Among researchers, there is some controversy about the most effective way of learning English from the viewpoint of the affective domain. The purpose of the present study was to investigate the potential relationship between students frequent use of English outside class and the degree of foreign language classroom anxiety (FLCA). Methods: A questionnaire including 45 five-point Likert scale items on the relationship between Japanese use and FLCA in task-based English classes was administered to 257 Japanese students attending a language-oriented university. Results: Increased use of English outside class was significantly related to lower FLCA, higher risk-taking, less preference to use Japanese, and higher enthusiasm. Additionally, lower FLCA was related to longer hours of English study (grammar, reading, listening and/or writing) at home and study abroad experience. Conclusions: The present results suggest that frequent use of English out of class with high enthusiasm may be useful for Japanese college students to have lower FLCA.

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記述言語：日本語   出版者・発行元：PLoS ONE  

Background Despite its recommendation by the current guidelines, the role of long-term oral beta-blocker therapy has never been evaluated by randomized trials in uncomplicated ST-segment elevation myocardial infarction (STEMI) patients without heart failure, left ventricular dysfunction or ventricular arrhythmia who underwent primary percutaneous coronary intervention (PCI). Methods and results In a multi-center, open-label, randomized controlled trial, STEMI patients with successful primary PCI within 24 hours from the onset and with left ventricular ejection fraction (LVEF) 40% were randomly assigned in a 1-to-1 fashion either to the carvedilol group or to the no beta-blocker group within 7 days after primary PCI. The primary endpoint is a composite of all-cause death, myocardial infarction, hospitalization for heart failure, and hospitalization for acute coronary syndrome. Between August 2010 and May 2014, 801 patients were randomly assigned to the carvedilol group (N = 399) or the no beta-blocker group (N = 402) at 67 centers in Japan. The carvedilol dose was up-titrated from 3.4±2.1 mg at baseline to 6.3 ±4.3 mg at 1-year. During median follow-up of 3.9 years with 96.4% follow-up, the cumulative 3-year incidences of both the primary endpoint and any coronary revascularization were not significantly different between the carvedilol and no beta-blocker groups (6.8% and 7.9%, P = 0.20, and 20.3% and 17.7%, P = 0.65, respectively). There also was no significant difference in LVEF at 1-year between the 2 groups (60.9±8.4% and 59.6±8.8%, P = 0.06) Conclusion Long-term carvedilol therapy added on the contemporary evidence-based medications did not seem beneficial in selected STEMI patients treated with primary PCI. Trial registration CAPITAL-RCT (Carvedilol Post-Intervention Long-Term Administration in Large-scale Randomized Controlled Trial) ClinicalTrials.gov.number, NCT 01155635.

DOI： 10.1371/journal.pone.0199347

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記述言語：日本語   出版者・発行元：Journal of the American Heart Association  

Background--Prediction of thrombotic and bleeding risk is important to optimize antithrombotic therapy after percutaneous coronary intervention. Methods and Results--We developed the prediction rules for thrombotic and bleeding events separately in Japanese patients. Derivation and validation cohorts consisted of 4778 patients from CREDO-Kyoto (Coronary Revascularization Demonstrating Outcome Study in Kyoto) registry cohort 2 and 4669 patients from RESET (Randomized Evaluation of Sirolimus-Eluting Versus Everolimus-Eluting Stent Trial) and NEXT (Nobori Biolimus-Eluting Versus Xience/Promus Everolimus-Eluting Stent Trial). Primary thrombotic and bleeding events were a composite of myocardial infarction, definite or probable stent thrombosis or ischemic stroke, and GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries) moderate or severe bleeding. The prediction rule for thrombosis assigned 2 points for severe chronic kidney disease, atrial fibrillation, peripheral vascular disease, and anemia and 1 point for age ≥75 years, heart failure, diabetes mellitus, and chronic total occlusion. The prediction rule for bleeding assigned 2 points for thrombocytopenia, severe chronic kidney disease, peripheral vascular disease, and heart failure and 1 point for prior myocardial infarction, malignancy, and atrial fibrillation. In derivation and validation cohorts, area under the curve was 0.68 and 0.64, respectively, for thrombosis and 0.66 and 0.66, respectively, for bleeding. In the validation cohort, a high thrombosis risk score (≥4, n=682) was associated with higher 3-year incidence of thrombotic events than a score that was intermediate (2-3, n=1178) or low (0-1, n=2809) (7.6%, 3.7%, versus 2.4%, respectively; P < 0.0001). A high bleeding risk score (≥3, n=666) was associated with higher incidence of bleeding than scores that were intermediate (1-2, n=1802) or low (0, n=2201) (8.8%, 4.1%, versus 2.3%, respectively; P < 0.0001). Among 682 patients at high thrombotic risk, only 39 (5.7%) had low bleeding risk, whereas 401 (58.8%) had high bleeding risk with very high incidence of bleeding (11.6%). Conclusions--CREDO-Kyoto thrombotic and bleeding risk scores demonstrated modest accuracy in stratifying thrombotic and bleeding risks; however, a large proportion of patients at high thrombotic risk also had high bleeding risk.

DOI： 10.1161/JAHA.118.008708

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記述言語：日本語   出版者・発行元：Brain and Nerve  

Akathisia consists of subjective inner restlessness, such as awareness of the inability to remain seated, restless legs, fidgetiness, and the desire to move constantly, and of objective increased motor phenomena, such as body rocking, shifting from foot to foot, stamping in place, crossing and uncrossing legs, pacing around. Although the broad definition of akathisia includes the inner and motor restlessness observed in patients with idiopathic Parkinson's disease, post-encephalitic parkinsonism, and restless legs syndrome, here we exclusively focus on the narrow definition of antipsychotic-induced akathisia. The most reliable treatment for acute akathisia is the reduction or the withdrawal of antipsychotic medication. However, this is often not possible because it may worsen the patients' mental condition. Various pharmacological agents have been used for the treatment of this condition. These include anticholinergic agents (e.g., biperiden and trihexyphenidyl), benzodiazepines, beta-adrenoceptor blockers (e.g., propranolol), and serotonin 2A receptor antagonists (e.g., mianserin, cyproheptadine, and mirtazapine).

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記述言語：日本語   出版者・発行元：JACC: Cardiovascular Interventions  

Objectives The purpose of this study was to evaluate long-term clinical impact of routine follow-up coronary angiography (FUCAG) after percutaneous coronary intervention (PCI) in daily clinical practice in Japan. Background The long-term clinical impact of routine FUCAG after PCI in real-world clinical practice has not been evaluated adequately. Methods In this prospective, multicenter, open-label, randomized trial, patients who underwent successful PCI were randomly assigned to routine angiographic follow-up (AF) group, in which patients were to receive FUCAG at 8 to 12 months after PCI, or clinical follow-up alone (CF) group. The primary endpoint was defined as a composite of death, myocardial infarction, stroke, emergency hospitalization for acute coronary syndrome, or hospitalization for heart failure over a minimum of 1.5 years follow-up. Results Between May 2010 and July 2014, 700 patients were enrolled in the trial among 22 participating centers and were randomly assigned to the AF group (n = 349) or the CF group (n = 351). During a median of 4.6 years of follow-up (interquartile range [IQR]: 3.1 to 5.2 years), the cumulative 5-year incidence of the primary endpoint was 22.4% in the AF group and 24.7% in the CF group (hazard ratio: 0.94; 95% confidence interval: 0.67 to 1.31; p = 0.70). Any coronary revascularization within the first year was more frequently performed in AF group than in CF group (12.8% vs. 3.8%; log-rank p < 0.001), although the difference between the 2 groups attenuated over time with a similar cumulative 5-year incidence (19.6% vs. 18.1%; log-rank p = 0.92). Conclusions No clinical benefits were observed for routine FUCAG after PCI and early coronary revascularization rates were increased within routine FUCAG strategy in the current trial. (Randomized Evaluation of Routine Follow-up Coronary Angiography After Percutaneous Coronary Intervention Trial [ReACT]; NCT01123291)

DOI： 10.1016/j.jcin.2016.10.018

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記述言語：日本語   出版者・発行元：Gastric Cancer  

Background: Although postoperative adjuvant chemotherapy with S-1, an oral fluoropyrimidine, has become a standard of care for gastric cancer in Japan, nonresponders may suffer from the cost and adverse reactions without clinical benefit. This multicenter exploratory phase II trial was conducted to see whether a chemosensitivity test, the collagen gel droplet embedded culture drug sensitivity test (CD-DST), can adequately select patients for chemotherapy. Methods: The CD-DST using four different concentrations of 5-fluorouracil was conducted with resected specimens from preregistered patients who underwent gastrectomy with D2 or more extensive lymphadenectomy. Patients who were histopathologically confirmed to have stage II or greater disease without distant metastasis were eligible for final enrollment. All patients underwent protocol-specified adjuvant chemotherapy with S-1. Three-year relapse-free survival was compared between patients determined as sensitive by the CD-DST (responders) and those deemed insensitive (nonresponders). Appropriate cutoff values for in vitro growth inhibition were defined when the hazard ratio for relapse in responders and the log-rank P values were at their minimum. Results: Of the 311 patients enrolled, 14 were ineligible and 27 failed to start the protocol treatment. The CD-DST failed in 64 other patients, and survival analyses were conducted with the remaining 206 patients (39 stage II disease, 155 stage III disease, and 12 stage IV disease). The outcome of patients who were determined to be responders was significantly superior to that of nonresponders regardless of the 5-fluorouracil concentrations, although no differences in clinicopathologic characteristics were observed between the two groups, except for age. Conclusions: The CD-DST identified those who benefit from adjuvant chemotherapy. It deserves further evaluation in the setting of a prospective randomized trial. ClinicalTrials.gov identifier: NCT00287755

DOI： 10.1007/s10120-015-0506-z

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：European Archives of Psychiatry and Clinical Neuroscience  

Persistent depression has been suggested to be associated with autistic traits in people of working age. This study aimed to clarify which autistic characteristics at the initial visit were associated with persistent depression at the 12 week follow-up in a primary care setting. Newly depressed outpatients aged 24–59 years with no history of autism were asked to complete the 50-item autism spectrum quotient (AQ) and the Beck depression inventory (BDI) at baseline and 12 week follow-up (N = 123, males: 48%, age: 37.7 ± 9.15 years). Nearly 40% of participants had an AQ score ≥ 26. Significant differences were observed between the group with remitted depression (N = 43) and those with persistent depression (N = 80) in educational years and AQ “attention switching” and “attention to detail” subscale scores. In addition, a statistically significant decrease in the total AQ and the “communication” and “imagination” scores were observed in the remitted group, while no such change was observed in the group with persistent depression. It remains unclear whether the self-perceived severity of communication and imagination traits in persistent depression was due to the state of persistent depression or a kind of premorbid autistic trait. The results suggest that high levels of autistic traits are frequently present in adults with depression. High “attention switching” and “attention to detail” scores in AQ screening at the first visit might predict the persistence of depressive symptoms after 12 weeks in adults with depression, while total AQ scores, especially for “communication” and “imagination” items, might be state-dependent.

DOI： 10.1007/s00406-021-01292-6

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Brain and Behavior  

Background: Violence in patients with delirium may occur suddenly and unpredictably in a fluctuating state of consciousness. Although various factors are involved, appropriate assessment and early response to factors related to violence in delirium are expected to prevent dangerous and distressing acts of violence against patients, their families and medical staff, and minimize the use of physical restraint and excessive drug sedation. Methods: Subjects were 601 delirium cases referred to the department of psychiatry over the course of 5 years at a general hospital. The demographic, clinical, and pharmacological variables of patients with violence (n = 189) were compared with those of patients without violence (n = 412). Logistic regression analysis was applied to determine whether any specific individual factors were associated with violence. Results: Current smoker status (p <.0005), older age (p <.0005), male gender (p =.004), and use of intensive care units (p =.043) were identified as factors associated with violence in patients with delirium. Conclusions: Screening tools for violence in patients with delirium and adequate management may assist in better outcomes for patients and medical staff. Further research should evaluate the usefulness of nicotine replacement treatment for the prevention of violence during nicotine withdrawal, including whether it is safe for elderly inpatients with a high incidence of delirium in clinical practice.

DOI： 10.1002/brb3.2276

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記述言語：日本語   出版者・発行元：(株)星和書店  

うつ病・うつ状態を評価するために様々な評価尺度が開発されている。なかでもハミルトンうつ病評価尺度やモンゴメリ・アスベルグうつ病評価尺度は精神科領域で広く使用されている。これらの尺度は、主としてうつ病患者の経時的な重症度の推移を評価する際に用いられ、臨床試験等における薬剤の有効性や臨床研究における改善や寛解等を示す指標として用いられている。一方で、特定の精神疾患を対象としてうつ状態を評価する目的で開発された評価尺度として、認知症患者を対象としたコーネル認知症抑うつ尺度、統合失調症患者を対象とした統合失調症カルガリー抑うつ尺度、双極性うつ病患者を対象とした双極性うつ病評価尺度などがある。このほか、抑うつ症状を1ポイントで評価する目的で開発された標準化うつ病臨床転帰尺度や、精神症状全般を評価する尺度の中に含まれるうつ状態に関連した評価項目について概観する。(著者抄録)

記述言語：日本語   出版者・発行元：(株)星和書店  

軽躁・躁病エピソードの既往が聴取されなければ、うつ病エピソードで受診する双極性うつ病の患者を単極性うつ病と鑑別することは容易ではない。両者は薬剤選択などの治療方針が異なり、双極性うつ病では抗うつ薬治療による気分変動や急速交代化など診断の遅れに伴う難治化をもたらすことから正しく評価する必要がある。さらに、双極性障害は病相が変化することから、治療経過中の症状モニタリングと臨機応変な治療方針の決定も欠かせない。現在、うつ病評価尺度のほとんどは単極性うつ病を評価するために考案された尺度であり、双極性うつ病を対象に用いる評価ツールとしては限界がある。本稿では、双極性うつ病を検出し、そのうつ症状の重症度を評価するために開発されたBipolar Depression Rating Scale(双極性うつ病評価尺度)の開発経緯や尺度について概説する。(著者抄録)

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Scientific Reports  

Delirium develops through a multifactorial process and include multiple subtypes with different pathological factors. To refine the treatment and care for delirium, a more detailed examination of these subtypes is needed. Therefore, this study aimed to explore the factors affecting delirium in cases in which hallucinations are conspicuous. In total, 602 delirium cases referred to the psychiatry department at a general hospital between May 2015 and August 2020 were enrolled. The Delirium Rating Scale-revised-98 was used to assess perceptual disturbances and hallucinations in patients with delirium. Multiple regression analysis was applied to determine whether individual factors were associated with the hallucinations. A total of 156 patients with delirium (25.9%) experienced hallucinations, with visual hallucinations being the most common subtype. Alcohol drinking (p < 0.0005), benzodiazepine withdrawal (p = 0.004), and the use of angiotensin II receptor blockers (p = 0.007) or dopamine receptor agonists (p = 0.014) were found to be significantly associated with hallucinations in patients with delirium. The four factors detected in this study could all be reversible contributing factors derived from the use of or withdrawal from exogenous substances.

DOI： 10.1038/s41598-021-92578-1

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Psychiatry Research  

Subjective attention deficit/hyperactivity disorder (ADHD) symptoms seen in adult depressive patients have often become a pathophysiological topic in recent years. Screening questionnaires are widely used for detecting ADHD; however, the risk of misdiagnosis exists. The present study examined whether self-perceptions of ADHD-related characteristics were consistent regardless of changes in the severity of depressive symptoms. Between April to October 2018, newly diagnosed depressed outpatients aged 24–59 years with good social functioning and without a history of ADHD were asked to fill out the Adult ADHD Self-Report Scale version 1.1 (ASRS) and the Beck Depression Inventory (BDI) at baseline (n = 726) and 12-week follow-up (n = 202). A statistically significant correlation was found between a change in BDI and ASRS scores (score at baseline minus score at the endpoint; r = .57). In addition, the higher the rate of improvement in BDI, the lower the frequency of positive screening for ADHD by ASRS. This study showed that subjective ADHD symptoms were correlated with depressive states. Diagnostic evaluation of comorbid ADHD using self-report scales in a primary care setting should be made with caution.

DOI： 10.1016/j.psychres.2021.113893

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

Background: The use of benzodiazepines (BZDs) causes delirium, especially in elderly people. For this reason, suvorexant has been recommended as the first-line hypnotic in elderly patients. The aim of this study was to determine whether the first-line use of suvorexant, instead of BZDs, decreases referrals for delirium in elderly patients. Methods: Since May 2016 at Nagoya Ekisaikai Hospital, suvorexant has been recommended as the first-line hypnotic instead of BZDs. In May 2017, suvorexant was adopted as the first-line hypnotic. The number of delirium cases referred to psychiatry was compared among three consecutive periods: period A (May 2015–April 2016), during which BZDs were mainly used for insomnia; period B (May 2016–April 2017), during which the use of suvorexant was recommended instead of BZDs; and period C (May 2017–April 2018), during which suvorexant was principally adopted as the first-line hypnotic for insomnia. Potential confounding factors that may affect the development of delirium were also examined during the three periods. Results: The number of delirium referral cases in elderly patients in each period decreased, from 133 in period A to 86 in period B and 53 in period C. The rate of delirium referral cases decreased significantly every year (P = 9.02 × 10−10). Almost no significant confounding factors other than hypnotics were detected during the three periods. Conclusion: The referrals for delirium in elderly patients decreased significantly after the hypnotic was changed from BZDs to suvorexant.

DOI： 10.1111/psyg.12672

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Psychiatric Research  

Attention-deficit hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders, characterized by a persistent pattern of inattention, hyperactivity, and impulsivity. Since the diagnosis of ADHD is defined by operational diagnostic criteria consisting of several clinical symptoms, a number of heterogeneous mechanisms have been considered to be implicated in its pathophysiology. Although no clinically reliable biomarkers are available for the diagnosis of ADHD, several plausible candidate biomarkers have been proposed based on recent advances in biochemistry and molecular biology. This review article summarizes potential peripheral biomarkers associated with ADHD, mainly from recently published case-control studies. These include 1) biochemical markers: neurotransmitters and their receptors, neurotrophic factors, serum electrolytes, and inflammation markers; 2) genetic and epigenetic markers: microRNA, mRNA expression, and peripheral DNA methylation; 3) physiological markers: eye movement and electroencephalography. It also discusses the limitations and future directions of these potential biomarkers for application in clinical practice.

DOI： 10.1016/j.jpsychires.2021.03.012

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Nordic Journal of Psychiatry  

Background: Network analysis provides a new viewpoint that explicates intertwined and interrelated symptoms into dynamic causal architectures of symptom clusters. This is a process called ‘symptomics’ and is concurrently applied to various areas of symptomatology. Aims: Using the data from Research on Asian Psychotropic Prescription Patterns for Antipsychotics (REAP-AP), we aimed to estimate a network model of extrapyramidal syndrome in patients with schizophrenia. Methods: Using data from REAP-AP, extrapyramidal symptoms of 1046 Asian patients with schizophrenia were evaluated using the nine items of the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS). The estimated network of the ordered-categorical DIEPSS items consisted of nodes (symptoms) and edges (interconnections). A community detection algorithm was also used to identify distinctive symptom clusters, and correlation stability coefficients were used to evaluate the centrality stability. Results: An interpretable level of node strength centrality was ensured with a correlation coefficient. An estimated network of extrapyramidal syndrome showed that 26 (72.2%) of all possible 35 edges were estimated to be greater than zero. Dyskinesia was most centrally situated within the estimated network. In addition, earlier antipsychotic-induced extrapyramidal symptoms were divided into three distinctive clusters–extrapyramidal syndrome without parkinsonism, postural instability and gait difficulty-dominant parkinsonism, and tremor-dominant parkinsonism. Conclusions: Our findings showed that dyskinesia is the most central domain in an estimated network structure of extrapyramidal syndrome in Asian patients with schizophrenia. These findings are consistent with the speculation that acute dystonia, akathisia, and parkinsonism could be the risk factors of tardive dyskinesia.

DOI： 10.1080/08039488.2020.1777462

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Translational Psychiatry  

Dysregulation of epigenetic processes involving histone methylation induces neurodevelopmental impairments and has been implicated in schizophrenia (SCZ) and autism spectrum disorder (ASD). Variants in the gene encoding lysine demethylase 4C (KDM4C) have been suggested to confer a risk for such disorders. However, rare genetic variants in KDM4C have not been fully evaluated, and the functional impact of the variants has not been studied using patient-derived cells. In this study, we conducted copy number variant (CNV) analysis in a Japanese sample set (2605 SCZ and 1141 ASD cases, and 2310 controls). We found evidence for significant associations between CNVs in KDM4C and SCZ (p = 0.003) and ASD (p = 0.04). We also observed a significant association between deletions in KDM4C and SCZ (corrected p = 0.04). Next, to explore the contribution of single nucleotide variants in KDM4C, we sequenced the coding exons in a second sample set (370 SCZ and 192 ASD cases) and detected 18 rare missense variants, including p.D160N within the JmjC domain of KDM4C. We, then, performed association analysis for p.D160N in a third sample set (1751 SCZ and 377 ASD cases, and 2276 controls), but did not find a statistical association with these disorders. Immunoblotting analysis using lymphoblastoid cell lines from a case with KDM4C deletion revealed reduced KDM4C protein expression and altered histone methylation patterns. In conclusion, this study strengthens the evidence for associations between KDM4C CNVs and these two disorders and for their potential functional effect on histone methylation patterns.

DOI： 10.1038/s41398-020-01107-7

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PLoS ONE  

Structural brain alterations have been repeatedly reported in schizophrenia; however, the pathophysiology of its alterations remains unclear. Multivariate pattern recognition analysis such as support vector machines can classify patients and healthy controls by detecting subtle and spatially distributed patterns of structural alterations. We aimed to use a support vector machine to distinguish patients with schizophrenia from control participants on the basis of structural magnetic resonance imaging data and delineate the patterns of structural alterations that significantly contributed to the classification performance. We used independent datasets from different sites with different magnetic resonance imaging scanners, protocols and clinical characteristics of the patient group to achieve a more accurate estimate of the classification performance of support vector machines. We developed a support vector machine classifier using the dataset from one site (101 participants) and evaluated the performance of the trained support vector machine using a dataset from the other site (97 participants) and vice versa. We assessed the performance of the trained support vector machines in each support vector machine classifier. Both support vector machine classifiers attained a classification accuracy of >70% with two independent datasets indicating a consistently high performance of support vector machines even when used to classify data from different sites, scanners and different acquisition protocols. The regions contributing to the classification accuracy included the bilateral medial frontal cortex, superior temporal cortex, insula, occipital cortex, cerebellum, and thalamus, which have been reported to be related to the pathogenesis of schizophrenia. These results indicated that the support vector machine could detect subtle structural brain alterations and might aid our understanding of the pathophysiology of these changes in schizophrenia, which could be one of the diagnostic findings of schizophrenia.

DOI： 10.1371/journal.pone.0239615

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Human Genome Variation  

Disabled 1 (DAB1) is an intracellular adaptor protein in the Reelin signaling pathway and plays an essential role in correct neuronal migration and layer formation in the developing brain. DAB1 has been repeatedly reported to be associated with neurodevelopmental disorders including schizophrenia (SCZ) and autism spectrum disorders (ASD) in genetic, animal, and postmortem studies. Recently, increasing attention has been given to rare single-nucleotide variants (SNVs) found by deep sequencing of candidate genes. In this study, we performed exon-targeted resequencing of DAB1 in 370 SCZ and 192 ASD patients using next-generation sequencing technology to identify rare SNVs with a minor allele frequency <1%. We detected two rare missense mutations (G382C, V129I) and then performed a genetic association study in a sample comprising 1763 SCZ, 380 ASD, and 2190 healthy control subjects. Although no statistically significant association with the detected mutations was observed for either SCZ or ASD, G382C was found only in the case group, and in silico analyses and in vitro functional assays suggested that G382C alters the function of the DAB1 protein. The rare variants of DAB1 found in the present study should be studied further to elucidate their potential functional relevance to the pathophysiology of SCZ and ASD.

DOI： 10.1038/s41439-020-00125-7

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Neurodevelopmental Disorders  

Background: Rare genetic variants contribute to the etiology of both autism spectrum disorder (ASD) and schizophrenia (SCZ). Most genetic studies limit their focus to likely gene-disrupting mutations because they are relatively easier to interpret their effects on the gene product. Interpretation of missense variants is also informative to some pathophysiological mechanisms of these neurodevelopmental disorders; however, their contribution has not been elucidated because of relatively small effects. Therefore, we characterized missense variants detected in NRXN1, a well-known neurodevelopmental disease-causing gene, from individuals with ASD and SCZ. Methods: To discover rare variants with large effect size and to evaluate their role in the shared etiopathophysiology of ASD and SCZ, we sequenced NRXN1 coding exons with a sample comprising 562 Japanese ASD and SCZ patients, followed by a genetic association analysis in 4273 unrelated individuals. Impact of each missense variant detected here on cell surface expression, interaction with NLGN1, and synaptogenic activity was analyzed using an in vitro functional assay and in silico three-dimensional (3D) structural modeling. Results: Through mutation screening, we regarded three ultra-rare missense variants (T737M, D772G, and R856W), all of which affected the LNS4 domain of NRXN1α isoform, as disease-associated variants. Diagnosis of individuals with T737M, D772G, and R856W was 1ASD and 1SCZ, 1ASD, and 1SCZ, respectively. We observed the following phenotypic and functional burden caused by each variant. (i) D772G and R856W carriers had more serious social disabilities than T737M carriers. (ii) In vitro assay showed reduced cell surface expression of NRXN1α by D772G and R856W mutations. In vitro functional analysis showed decreased NRXN1α-NLGN1 interaction of T737M and D772G mutants. (iii) In silico 3D structural modeling indicated that T737M and D772G mutations could destabilize the rod-shaped structure of LNS2-LNS5 domains, and D772G and R856W could disturb N-glycan conformations for the transport signal. Conclusions: The combined data suggest that missense variants in NRXN1 could be associated with phenotypes of neurodevelopmental disorders beyond the diagnosis of ASD and/or SCZ.

DOI： 10.1186/s11689-020-09325-2

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Translational Psychiatry  

Schizophrenia (SCZ) is known to be a heritable disorder; however, its multifactorial nature has significantly hampered attempts to establish its pathogenesis. Therefore, in this study, we performed genome-wide copy-number variation (CNV) analysis of 2940 patients with SCZ and 2402 control subjects and identified a statistically significant association between SCZ and exonic CNVs in the ARHGAP10 gene. ARHGAP10 encodes a member of the RhoGAP superfamily of proteins that is involved in small GTPase signaling. This signaling pathway is one of the SCZ-associated pathways and may contribute to neural development and function. However, the ARHGAP10 gene is often confused with ARHGAP21, thus, the significance of ARHGAP10 in the molecular pathology of SCZ, including the expression profile of the ARHGAP10 protein, remains poorly understood. To address this issue, we focused on one patient identified to have both an exonic deletion and a missense variant (p.S490P) in ARHGAP10. The missense variant was found to be located in the RhoGAP domain and was determined to be relevant to the association between ARHGAP10 and the active form of RhoA. We evaluated ARHGAP10 protein expression in the brains of reporter mice and generated a mouse model to mimic the patient case. The model exhibited abnormal emotional behaviors, along with reduced spine density in the medial prefrontal cortex (mPFC). In addition, primary cultured neurons prepared from the mouse model brain exhibited immature neurites in vitro. Furthermore, we established induced pluripotent stem cells (iPSCs) from this patient, and differentiated them into tyrosine hydroxylase (TH)-positive neurons in order to analyze their morphological phenotypes. TH-positive neurons differentiated from the patient-derived iPSCs exhibited severe defects in both neurite length and branch number; these defects were restored by the addition of the Rho-kinase inhibitor, Y-27632. Collectively, our findings suggest that rare ARHGAP10 variants may be genetically and biologically associated with SCZ and indicate that Rho signaling represents a promising drug discovery target for SCZ treatment.

DOI： 10.1038/s41398-020-00917-z

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PLoS ONE  

Introduction A history of major depressive disorder before pregnancy is one risk factor for peripartum depression. Therefore, the purpose of the present study was to examine the validation and factor structure of the Japanese version of the Inventory to Diagnose Depression, Lifetime version (IDDL) for pregnant women. Methods The study participants were 556 pregnant women. Factor analysis was performed to identify the factor structure, construct validity was examined based on the results of the factor analysis, and reliability was examined using Cronbach's α coefficient. Results Based on the results of the factor analysis of the IDDL, a bifactor model composed of a single general dimension along with the following five factors was extracted: (1) depression, anxiety, and irritability (items 1, 2, 8-10, and 19-21); (2) retardation, decreased concentration, indecisiveness, and insomnia (items 4, 11, 12, and 17); (3) decrease in appetite/significant weight loss (items 13 and 14); (4) increase in appetite/significant weight gain (items 15 and 16); and (5) diminished interest, pleasure, and libido (items 5-7). Cronbach's α coefficients for these five factors were as follows: 0.910, 0.815, 0.780, 0.683, and 0.803, respectively. Conclusions The reliability, construct validity, and factor structure of the Japanese version of the IDDL were confirmed in pregnant women.

DOI： 10.1371/journal.pone.0234240

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Frontiers in Psychiatry  

Introduction: The aim of the present study was to elucidate the foreseeable risk factors for suicidal ideation among Japanese perinatal women. Methods: This cohort study was conducted in Nagoya, Japan, from July 2012 to March 2018. The Edinburgh Postnatal Depression Scale (EPDS) questionnaire was conducted at four time points: early pregnancy, late pregnancy, 5 days postpartum, and 1 month postpartum. A total of 430 women completed the questionnaires. A logistic regression analysis was performed using the presence of suicidal ideation on the EPDS as an objective variable. The explanatory variables were age, presence of physical or mental disease, smoking and drinking habits, education, hospital types, EPDS total score in early pregnancy, bonding, and quality and amount of social support, as well as the history of major depressive disorder (MDD). Results: The rate of participants who were suspected of having suicidal ideation at any of the four time points was 11.6% (n=52), with the highest (n=25, 5.8%) at late pregnancy. For suicidal ideation, education level (OR: 1.19; 95% CI: 1.00–1.41; p=0.047), EPDS total points in the pregnancy period (OR: 1.25; 95% CI: 1.16–1.34; p < 0.000), a history of MDD (OR: 2.16; 95% CI: 1.00–4.79; p=0.049), and presence of mental disease (OR: 2.39; 95% CI: 1.00–5.70; p=0.049) were found to be risk factors for suicidal ideation. Age [odds ratio (OR): 0.88; 95% confidence interval (CI): 0.80–0.95; p=.002] and quality of social support (OR: 0.77; 95% CI: 0.60–0.99; p=.041) were found to be protective factors. Conclusion: Based on these results, effective preventive interventions, such as increasing the quality of social support and confirming the history of depression, should be carried out in pregnant depressive women at the early stage of the perinatal period.

DOI： 10.3389/fpsyt.2020.00441

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Current Pharmaceutical Design  

Background: Methamphetamine (METH) is one of the most widely distributed psychostimulants worldwide. Despite active counter measures taken by different countries, neither overall usage of METH nor the frequency of repeat users has reduced over the past decade. METH induces abuse and dependence as it acts on the central nervous system and temporarily stimulates the brain. The recidivism rate for abuse of stimulants in Japan is very high and therefore prevention of repeated usage is paramount. However, we lack information about the relationship between METH users and genomic changes in humans in Japan, which would provide important information to aid such efforts. Objective: Shati/Nat8l is a METH-inducible molecule and its overexpression has protective effects on the brain upon METH usage. Here we investigated the effect of METH usage on DNA methylation rates at the promoter site of SHATI/NAT8L. We used DNA samples from human METH users, who are usually difficult to recruit in Japan. Methods: We measured DNA methylation at SHATI/NAT8L promoter sites by pyrosequencing method using 193 samples of METH users and 60 samples of healthy subjects. In this method, DNA methylation is measured by utilizing the property that only non-methylated cytosine changes to urasil after bisulfite conversion. Results: We found that the rate of DNA methylation at six CpG islands of SHATI/NAT8L promoter sites is significantly higher in METH users when compared to healthy subjects. Conclusion: These results suggest that the DNA methylation rate of SHATI/NAT8L promotor regions offers a new diagnostic method for METH usage.

DOI： 10.2174/1381612826666200110111703

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Psychiatria Danubina  

Background: Although an inverse relationship between body mass index (BMI) and Parkinson disease (PD) has been repeatedly reported, to our knowledge, the relationship between BMI and antipsychotic-induced extrapyramidal symptoms (EPS) has rarely been studied in patients with schizophrenia. Our study aimed to evaluate the relationship between BMI and EPS in patients with schizophrenia. Subjects and methods: Using data from the Research on Asian Psychotropic Prescription Patterns for Antipsychotics (REAP-AP) study, we compared the prevalence of EPS in 1448 schizophrenia patients stratified as underweight, normal range, overweight preobese, overweight obese I, overweight obese II, and overweight obese III according to the World Health Organization (WHO) classification system for body weight status, and with underweight, normal range, overweight at risk, overweight obese I, and overweight obese II according to the Asia-Pacific obesity classification. Results: In the first step of the WHO classification system for body weight status, adjusting for the potential effects of confounding factors, the multinomial logistic regression model revealed that underweight was significantly associated with greater rates of bradykinesia and muscle rigidity, and a lower rate of gait disturbance. In the second step of the Asia-Pacific obesity classification, adjusting for the potential effects of confounding factors, the multinomial logistic regression model revealed that underweight was significantly associated with a higher rate of muscle rigidity. Conclusion: Findings of the present study consistently revealed that underweight was associated with a greater rate of muscle rigidity in a stepwise pattern among Asian patients with schizophrenia. Although the mechanism underlying the inverse relationship between BMI and muscle rigidity cannot be sufficiently explained, it is speculated that low BMI may contribute to the development of muscle rigidity regardless of antipsychotic "typicality" and dose in patients with schizophrenia.

DOI： 10.24869/psyd.2020.176

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Nordic Journal of Psychiatry  

Background: The Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) is a multidimensional rating scale designed for the fast, easy and reliable assessment of extrapyramidal symptoms (EPSs) induced by antipsychotics. Aim: The aim of this study was to validate the level of inter-rater and test–retest reliability of the Norwegian translation of this scale. Methods: A total of 125 video clips showing a variety of or no signs of EPSs were used in the present study. The participants recorded were Japanese psychiatric patients receiving first- and/or second-generation antipsychotics. A total of 103 patients (47 males and 56 females), diagnosed with schizophrenia (n = 68) or mood disorders (n = 35) appeared in the video clips. Their mean age was 48.7 ± 16.3 years (range 18–80) at the time of video recording. Inter-rater agreement was assessed with five raters and test–retest reliability with three. Results: Inter-rater reliability analyses showed interclass correlation coefficients (ICCs) ranging from 0.74 to 0.93 for each individual item. Test–retest reliability analysed independently for each rater ranged from 0.71 to 0.96. Conclusions: Inter-rater and test–retest agreement exhibited satisfactory ICC levels above 0.70. The Norwegian version of the DIEPSS is a reliable instrument for the assessment of drug-induced EPSs.

DOI： 10.1080/08039488.2019.1665708

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Nordic Journal of Psychiatry  

Background: Although cannabis use has been linked with schizophrenia in a dose–response pattern, to our knowledge, the relationship between cannabis and schizophrenia has rarely been reported in Asian population. Aim: We compared the clinical characteristics and psychotropic prescription patterns between cannabis users and non-users among Asian patients with schizophrenia. Moreover, we aimed to identify the independent correlates of cannabis use in these subjects. Methods: We performed the analysis of the data from the Research on Asian Psychotropic Prescription Patterns for Antipsychotics (REAP-AP), a collaborative consortium survey used to collate the prescription patterns for antipsychotic and other psychotropic medications in patients with schizophrenia in Asia. We included 132 schizophrenia patients in the group of lifetime cannabis use and 1756 in the group that had never used cannabis. A binary logistic model was fitted to detect the clinical correlates of lifetime cannabis use. Results: Adjusting for the effects of age, sex, geographical region, income group, duration of untreated psychosis, and Charlson comordity index level, a binary logistic regression model revealed that lifetime cannabis use was independently associated with aggressive behavior [adjusted odds ratio (aOR) = 1.582, 95% confidence interval (CI) = 1.006–2.490, p =.047] and with long-acting injectable antipsychotic treatment (aOR = 1.796, 95% CI = 1.444–2.820, p =.001). Conclusion: Our findings indicate a close link between lifetime cannabis use and aggressive behavior. The use of long-acting, injectable antipsychotics preferentially treats the aggressive behavior cannabis users among patients with schizophrenia in Asia, especially, the South or Southeast Asia.

DOI： 10.1080/08039488.2019.1632381

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3389/fpsyt.2019.00515

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

Studies of eye movement have become an essential tool of basic neuroscience research. Measures of eye movement have been applied to higher brain functions such as cognition, social behavior, and higher-level decision-making. With the development of eye trackers, a growing body of research has described eye movements in relation to mental disorders, reporting that the basic oculomotor properties of patients with mental disorders differ from those of healthy controls. Using discrimination analysis, several independent research groups have used eye movements to differentiate patients with schizophrenia from a mixed population of patients and controls. Recently, in addition to traditional oculomotor measures, several new techniques have been applied to measure and analyze eye movement data. One research group investigated eye movements in relation to the risk of autism spectrum disorder several years prior to the emergence of verbal-behavioral abnormalities. Research on eye movement in humans in social communication is therefore considered important, but has not been well explored. Since eye movement patterns vary between patients with mental disorders and healthy controls, it is necessary to collect a large amount of eye movement data from various populations and age groups. The application of eye trackers in the clinical setting could contribute to the early treatment of mental disorders.

DOI： 10.1002/npr2.12046

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記述言語：日本語   出版者・発行元：(公社)日本精神神経学会  

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Scientific Reports  

Early detection of perinatal depression is an urgent issue. Our study aimed to examine the construct validity and factor structure of the Japanese version of the Edinburgh Postnatal Depression Scale (EPDS) from a prospective cohort study from pregnancy to postpartum. A total of 1075 women completed all items of the EPDS at four time points: early pregnancy, late pregnancy, 5 days postpartum and 1 month postpartum. The participants were randomly divided into two sample sets. The first sample set (n = 304) was used for exploratory factor analysis, and the second sample set (n = 771) was used for confirmatory factor analysis. As a result, the Cronbach’s alpha coefficients of the EPDS items were 0.762, 0.740, 0.765 and 0.772 at the four time points. From the confirmatory factor analysis of the EPDS in a sample set of Japanese women from pregnancy to postpartum, the following three factors were detected: depression (items 7, 9), anxiety (items 4, 5) and anhedonia (items 1, 2). In conclusion, the EPDS is a useful rating scale, and its factor structure is consistently stable during the whole peripartum period.

DOI： 10.1038/s41598-018-36101-z

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Psychiatric Genetics  

Enhanced carbonyl stress has been observed in a subgroup of patients with schizophrenia. Glyoxalase I, which is encoded by GLO1, is an enzyme that protects against carbonyl stress. In this study, we focused on the association between rare genetic variants of GLO1 and schizophrenia. First, we identified one heterozygous frameshift variant, p.P122fs, in 370 Japanese schizophrenia cases with allele frequencies of up to 1% by exon-targeted mutation screening of GLO1. We then performed an association analysis on 1282 cases and 1764 controls with this variant. The variant was found in three cases and eight controls. There was no statistically significant association between p.P122fs in GLO1 and schizophrenia (P=0.25). This frameshift variant in GLO1 might occur at near-polymorphic frequencies in the Japanese population, although further investigations using larger samples and biological analyses are needed to exclude the possibility of a low-penetrance genetic risk associated with this variant.

DOI： 10.1097/YPG.0000000000000204

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Cell Reports  

Compelling evidence in Caucasian populations suggests a role for copy-number variations (CNVs) in autism spectrum disorder (ASD) and schizophrenia (SCZ). We analyzed 1,108 ASD cases, 2,458 SCZ cases, and 2,095 controls in a Japanese population and confirmed an increased burden of rare exonic CNVs in both disorders. Clinically significant (or pathogenic) CNVs, including those at 29 loci common to both disorders, were found in about 8% of ASD and SCZ cases, which was significantly higher than in controls. Phenotypic analysis revealed an association between clinically significant CNVs and intellectual disability. Gene set analysis showed significant overlap of biological pathways in both disorders including oxidative stress response, lipid metabolism/modification, and genomic integrity. Finally, based on bioinformatics analysis, we identified multiple disease-relevant genes in eight well-known ASD/SCZ-associated CNV loci (e.g., 22q11.2, 3q29). Our findings suggest an etiological overlap of ASD and SCZ and provide biological insights into these disorders. Kushima et al. perform comparative analyses of CNVs in ASD and SCZ in a Japanese population. They identify pathogenic CNVs and biological pathways in each disorder with significant overlap. Patients with pathogenic CNVs have a higher prevalence of intellectual disability. Disease-relevant genes are detected in eight well-known ASD/SCZ-associated CNV loci.

DOI： 10.1016/j.celrep.2018.08.022

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Psychiatry Research - Neuroimaging  

Resting-state (rs) functional magnetic resonance imaging (fMRI) studies have revealed dysfunctional thalamocortical functional connectivity (FC) in schizophrenia. However, the relationship between thalamocortical FC and cognitive impairment has not been thoroughly investigated. We hypothesized that aberrant thalamocortical FC is related to attention deficits in schizophrenia. Thirty-eight patients with schizophrenia and 38 matched healthy controls underwent rs-fMRI and task fMRI while performing a Flanker task. We observed decreased left thalamic activation in patients with schizophrenia using task fMRI to determine the thalamic seed. A seed-based analysis using this seed was performed in the whole brain to assess differences in thalamocortical FC between the groups. Significantly worse performance was observed in the patient group. The rs-fMRI analysis revealed significantly increased FC between the left thalamus seed and the occipital cortices/postcentral gyri in patients when compared to controls. In the patient group, significant positive correlations were observed between the degree of FC from the left thalamus to the bilateral occipital gyri, which correspond to the visual cortex, and the Flanker effect. No significant correlation was detected in the control group. These results indicate that aberrant FC between the left thalamus and the visual cortex is related to attention deficits in schizophrenia.

DOI： 10.1016/j.pscychresns.2018.06.007

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Molecular Psychiatry  

Genome-wide association studies (GWASs) have identified several susceptibility loci for bipolar disorder (BD) and shown that the genetic architecture of BD can be explained by polygenicity, with numerous variants contributing to BD. In the present GWAS (Phase I/II), which included 2964 BD and 61 887 control subjects from the Japanese population, we detected a novel susceptibility locus at 11q12.2 (rs28456, P=6.4 × 10 '9), a region known to contain regulatory genes for plasma lipid levels (FADS1/2/3). A subsequent meta-analysis of Phase I/II and the Psychiatric GWAS Consortium for BD (PGC-BD) identified another novel BD gene, NFIX (P best =5.8 × 10 '10), and supported three regions previously implicated in BD susceptibility: MAD1L1 (P best =1.9 × 10 '9), TRANK1 (P best =2.1 × 10 '9) and ODZ4 (P best =3.3 × 10 '9). Polygenicity of BD within Japanese and trans-European-Japanese populations was assessed with risk profile score analysis. We detected higher scores in BD cases both within (Phase I/II) and across populations (Phase I/II and PGC-BD). These were defined by (1) Phase II as discovery and Phase I as target, or vice versa (for 'within Japanese comparisons', P best ∼10 '29, R 2 ∼2%), and (2) European PGC-BD as discovery and Japanese BD (Phase I/II) as target (for 'trans-European-Japanese comparison,' P best ∼10 '13, R 2 ∼0.27%). This 'trans population' effect was supported by estimation of the genetic correlation using the effect size based on each population (liability estimates∼0.7). These results indicate that (1) two novel and three previously implicated loci are significantly associated with BD and that (2) BD 'risk' effect are shared between Japanese and European populations.

DOI： 10.1038/mp.2016.259

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：株式会社医学書院  

DOI： 10.11477/mf.1416200927

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CiNii Research

DOI： 10.1038/tp.2017.170

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Scientific Reports  

Drug-induced Extrapyramidal Symptoms Scale (DIEPSS) is developed in the era of second-generation antipsychotics and is suitable for evaluation of the low incidence of extrapyramidal symptoms occurring in the treatment of atypical antipsychotics, as well as the relationship between personal and social functioning. The study was carried out at the Institute of Mental Health in Serbia in 2015 Study used the 127 DIEPSS video clips material, recorded from 1987 till 2015. Four raters performed the assessment simultaneously, individually rating one assigned item immediately after seeing the video clip. For the purpose of evaluating test-retest reliability the second assessment of the same material was performed nine months after the first assessment. Inter-rater reliability was high for each individual item, with ICCs ranging from 0.769 to 0.949. The inter-rater reliability was highest for akathisia item and lowest for dyskinesia. The test-retest reliability was high for each individual item, with ICC ranging from 0.713 to 0.935. The test-retest reliability was highest for bradykinesia item and lowest for dystonia. The Serbian version of DIEPSS has high level of inter-rater and test-retest reliability. High values of concordance rates (ICC > 0.7) for each evaluated individual item suggest that items of DIEPSS are well defined.

DOI： 10.1038/s41598-017-08706-3

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記述言語：日本語   出版者・発行元：Translational Psychiatry  

CX3CR1, a G protein-coupled receptor solely expressed by microglia in the brain, has been repeatedly reported to be associated with neurodevelopmental disorders including schizophrenia (SCZ) and autism spectrum disorders (ASD) in transcriptomic and animal studies but not in genetic studies. To address the impacts of variants in CX3CR1 on neurodevelopmental disorders, we conducted coding exon-targeted resequencing of CX3CR1 in 370 Japanese SCZ and 192 ASD patients using next-generation sequencing technology, followed by a genetic association study in a sample comprising 7054 unrelated individuals (2653 SCZ, 574 ASD and 3827 controls). We then performed in silico three-dimensional (3D) structural modeling and in vivo disruption of Akt phosphorylation to determine the impact of the detected variant on CX3CR1-dependent signal transduction. We detected a statistically significant association between the variant Ala55Thr in CX3CR1 with SCZ and ASD phenotypes (odds ratio=8.3, P=0.020). A 3D structural model indicated that Ala55Thr could destabilize the conformation of the CX3CR1 helix 8 and affect its interaction with a heterotrimeric G protein. In vitro functional analysis showed that the CX3CR1-Ala55Thr mutation inhibited cell signaling induced by fractalkine, the ligand for CX3CR1. The combined data suggested that the variant Ala55Thr in CX3CR1 might result in the disruption of CX3CR1 signaling. Our results strengthen the association between microglia-specific genes and neurodevelopmental disorders.

DOI： 10.1038/tp.2017.173

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その他リンク： http://www.nature.com/articles/tp2017173

記述言語：日本語   出版者・発行元：International Journal of Neuropsychopharmacology  

DOI： 10.1093/ijnp/pyx020

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記述言語：日本語   出版者・発行元：Schizophrenia Research  

DOI： 10.1016/j.schres.2016.08.023

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記述言語：日本語 著書種別：学術書

その他リンク： https://www.amazon.co.jp/YMRS%E3%82%92%E4%BD%BF%E3%81%84%E3%81%93%E3%81%AA%E3%81%99_%E3%83%A4%E3%83%B3%E3%82%B0%E8%BA%81%E7%97%85%E8%A9%95%E4%BE%A1%E5%B0%BA%E5%BA%A6%E6%97%A5%E6%9C%AC%E8%AA%9E%E7%89%88-YMRS-J-%E3%81%AB%E3%82%88%E3%82%8B%E8%BA%81%E7%97%85%E3%81%AE%E8%87%A8%E5%BA%8A%E8%A9%95%E4%BE%A1-%E7%A8%B2%E7%94%B0-%E4%BF%8A%E4%B9%9F/dp/4840743428/ref=sr_1_1?s=books&ie=UTF8&qid=1490582925&sr=1-1&keywords=YMRS%E3%82%92%E4%BD%BF%E3%81%84%E3%81%93%E3%81%AA%E3%81%99

記述言語：日本語 著書種別：学術書

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記述言語：英語 著書種別：学術書

記述言語：日本語

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記述言語：日本語

CiNii Books

記述言語：日本語

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