記述言語：英語   出版者・発行元：Neuropsychopharmacology Reports  

Background: Catatonia is a syndrome that may present with stupor, immobility, and postural retention, and appears in various primary disorders including schizophrenia, depressive disorders, and neurodevelopmental disorders. Case presentation: In this report, we describe a 34-year-old female patient with schizophrenia, who had previously been treated with antipsychotic agents to improve psychotic symptoms with delusional symptoms and catatonia. However, she relapsed with catatonic symptoms around 1 year after she voluntarily discontinued the prescribed antipsychotic medications by herself. Her catatonia was successfully improved using the transdermal blonanserin patch, a drug formulation globally first approved in Japan in 2019. Discussion: Although benzodiazepines or electroconvulsive therapy have been recommended as the first-line treatment of catatonic manifestation observed in psychiatric patients, this patient responded well to antipsychotic blonanserin. From the differential drug responses, catatonia may be the complex of heterogeneous conditions with different pathophysiologies.

DOI： 10.1002/npr2.12314

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記述言語：英語   出版者・発行元：Psychogeriatrics  

The course of delirium is associated with increased hospital costs, healthcare complications, increased mortality, and long-term poor outcomes. Despite delirium being long recognised as one of the most important prognostic components of patients with illnesses, delirium remains poorly understood, effective management options are limited, and no effective treatment has yet been established. This review evaluated the effects of delirium on mortality, institutionalisation, and dementia in various situations to clarify its prognostic seriousness to elucidate important areas for clinical practice and future research. The effect of delirium on mortality in COVID-19 patients was similar to that in other diseases. The effect of delirium on mortality in patients with delirium between the ages of 18 and 65 may be higher than in those with delirium aged over 65, but studies are scarce. Promoting recognition of delirium at all ages is needed. With careful attention to the specific factors in younger patients that contribute to delirium, healthcare providers may be able to decrease the poor impact of delirium on clinical outcomes. Evaluation of the association between interventions for delirium such as sedation in present clinical practice and the prognosis of delirium is lacking, and further clinical studies are essential.

DOI： 10.1111/psyg.12914

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

Aim: The present study aimed to examine the association between copy number variations (CNVs) in parkin (PRKN) and schizophrenia (SCZ) and autism spectrum disorder (ASD) in a large case–control sample. Method: Array comparative genomic hybridization was performed on 3111 cases with SCZ, 1236 cases with ASD, and 2713 controls. We systematically prioritized likely pathogenic CNVs (LP-CNVs) in PRKN and examined their association with SCZ and ASD. Results: In total, 3014 SCZ cases (96.9%), 1205 ASD cases (97.5%), and 2671 controls (98.5%) passed quality control. We found that monoallelic carriers of LP-CNVs in PRKN were common (70/6890, 1.02%) and were not at higher risk of SCZ (p = 0.29) or ASD (p = 0.72). We observed that the distribution pattern of LP-CNVs in the Japanese population was consistent with those in other populations. We also identified a patient diagnosed with SCZ and early-onset Parkinson's disease carrying biallelic pathogenic CNVs in PRKN. The absence of Parkinson's symptoms in 10 other monoallelic carriers of the same pathogenic CNV further reflects the lack of effect of monoallelic pathogenic variants in PRKN in the absence of a second hit. Conclusion: The present findings suggest that monoallelic CNVs in PRKN do not confer a significant risk for SCZ or ASD. However, further studies to investigate the association between biallelic CNVs in PRKN and SCZ and ASD are warranted.

DOI： 10.1002/npr2.12370

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Psychiatry Research Communications  

Depression is the greatest estimated cause of disability among people of working age. Preventing dropouts from depression treatment in the early stages of outpatient psychiatric care is important in avoiding poor outcomes. Since the long waiting time between appointment and consultation was one of the factors for dropout in previous studies, this study aimed to determine the early dropout rate and identify factors associated with early treatment discontinuation in depressed patients in a psychiatric outpatient practice, where immediate access to treatment is available. Of 563 participants, 184 (32.7%) stopped treatment within 1 month, which was as high as previous findings. Logistic regression analysis confirmed that younger age, ICD-10 F4 diagnosis, and lower attention-deficit/hyperactivity disorder (ADHD)-related characteristics predicted earlier treatment discontinuation. The current study suggests that immediate access to treatment might not significantly affect the rate of treatment discontinuation within 1 month for working-age depressed patients. Given the high rate of early treatment discontinuation, explaining the importance of continuing treatment might be necessary at the first visit, especially for patients with younger age, ICD-10 F4 diagnosis, and fewer complaints suggestive of ADHD.

DOI： 10.1016/j.psycom.2023.100128

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記述言語：英語   出版者・発行元：Neuropsychopharmacology Reports  

Background: Chromosome 16p13.11 duplication is a well-known genetic risk factor for schizophrenia (SCZ) (odds ratio = 1.84). However, no case reports focusing on patients with SCZ and 16p13.11 duplication have been published. Therefore, here, we report the detailed clinical cases of four patients with SCZ and 16p13.11 duplication who were identified in our previous whole-genome copy number variant (CNV) study. Case Presentation: In the four patients with SCZ and 16p13.11 duplication detected by array comparative genomic hybridization, one patient was found to have treatment-resistant SCZ and an additional pathogenic rare CNV. Two of the four patients in this study had environmental risk factors that may have been involved in the development of SCZ. Conclusions: The results of this case series suggest that a genetic cohort study would be useful for evaluating which genetic and environmental risk factors could better explain the variable expressivity of 16p13.11 duplication. Furthermore, this work could be useful for elucidating the pathophysiology of SCZ.

DOI： 10.1002/npr2.12334

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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：Human Psychopharmacology  

Introduction: Drug-induced extrapyramidal syndrome (EPS) remains a major problem in clinical psychiatry. This study aimed to examine the factor structure of drug-induced extrapyramidal symptoms observed in patients with schizophrenia and assessed using the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS). Methods: The participants were 1478 patients with a diagnosis of schizophrenia whose EPS was assessed using the DIEPSS in India, Indonesia, Japan, Malaysia, and Taiwan in the 2016 REAP AP-4 study. The records of the participants were randomly divided into two subgroups: the first for exploratory factor analysis of the eight DIEPSS items, and the second for confirmatory factor analysis. Results: The factor analysis identified three factors: F1 (gait and bradykinesia), F2 (muscle rigidity and tremor), and F3 (sialorrhea, akathisia, dystonia, and dyskinesia). Conclusion: The results suggest that the eight individual items of the DIEPSS could be composed of three different mechanisms: acute parkinsonism observed during action (F1), acute parkinsonism observed at rest (F2), and central dopaminergic mechanisms with pathophysiology other than acute parkinsonism (F3).

DOI： 10.1002/hup.2861

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その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/hup.2861

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

This review aimed to clarify whether antimanic agents used in Japan are superior to placebo for the treatment of acute mania, based on reports of randomized controlled trials (RCTs) conducted in Japan and other East Asian countries. A literature search was conducted using the MEDLINE, PubMed, and Ichushi databases from their dates of inception to July 31, 2021, for studies written in English or Japanese with a primary diagnosis of bipolar I disorder, comparing any of the following active drugs to treat acute mania in adults: aripiprazole, carbamazepine, chlorpromazine, haloperidol, lithium, olanzapine, sultopride, timiperone, and zotepine. A random-effects network meta-analysis was performed within a frequentist framework. The quality of each included study was evaluated using the revised Cochrane risk-of-bias tool for randomized trials. The outcomes adopted were the response rate for efficacy and dropout rate for tolerability during 3 weeks from baseline. Eleven RCTs, totaling 1148 participants, were reviewed. The pooled odds ratio (OR) (±95% confidence interval [CI]) was calculated. Timiperone (OR = 4.53, CI 1.09–18.80), sultopride (OR = 3.76, CI 1.08–13.05), and aripiprazole (OR = 1.99, CI 1.22–3.24) were significantly more effective than placebo. Olanzapine (OR = 0.51, CI 0.29–0.90) was significantly superior in acceptability to placebo. The results showed no significant differences from placebo for carbamazepine, chlorpromazine, haloperidol, lithium, and olanzapine. These results suggest that noninferiority trials alone cannot always confirm the antimanic drug efficacy and that direct placebo-controlled trials are necessary to verify the antimanic efficacy of the drugs.

DOI： 10.1002/pcn5.60

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その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/pcn5.60

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

Aim: The aims of the present study were: (i) to examine the association between schizophrenia (SCZ) and 47, XXY or 47, XXX in a large case–control sample; and (ii) to characterize the clinical features of patients with SCZ with these X chromosome aneuploidies. Methods: To identify 47, XXY and 47, XXX, array comparative genomic hybridization (aCGH) was performed in 3188 patients with SCZ and 3586 controls. We examined the association between 47, XXY and 47, XXX and SCZ in males and females separately using exact conditional tests to control for platform effects. Clinical data were retrospectively examined for patients with SCZ with X chromosome aneuploidies. Results: Of the analyzed samples, 3117 patients (97.8%) and 3519 controls (98.1%) passed our quality control. X chromosome aneuploidies were exclusively identified in patients: 47, XXY in seven patients (0.56%), 47, XXX in six patients (0.42%). Statistical analysis revealed a significant association between SCZ and 47, XXY (P = 0.028) and 47, XXX (P = 0.011). Phenotypic data were available from 12 patients. Treatment-resistance to antipsychotics and manic symptoms were observed in six patients each (four with 47, XXY and two with 47, XXX for both), respectively. Statistical analysis revealed that treatment-resistance to antipsychotics, mood stabilizer use, and manic symptoms were significantly more common in patients with 47, XXY than in male patients without pathogenic copy number variations. Conclusion: These findings indicate that both 47, XXY and 47, XXX are significantly associated with risk for SCZ. Patients with SCZ with 47, XXY may be characterized by treatment-resistance and manic symptoms.

DOI： 10.1111/pcn.13474

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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：Biological Psychiatry  

Background: We aimed to determine the similarities and differences in the roles of genic and regulatory copy number variations (CNVs) in bipolar disorder (BD), schizophrenia (SCZ), and autism spectrum disorder (ASD). Methods: Based on high-resolution CNV data from 8708 Japanese samples, we performed to our knowledge the largest cross-disorder analysis of genic and regulatory CNVs in BD, SCZ, and ASD. Results: In genic CNVs, we found an increased burden of smaller (<100 kb) exonic deletions in BD, which contrasted with the highest burden of larger (>500 kb) exonic CNVs in SCZ/ASD. Pathogenic CNVs linked to neurodevelopmental disorders were significantly associated with the risk for each disorder, but BD and SCZ/ASD differed in terms of the effect size (smaller in BD) and subtype distribution of CNVs linked to neurodevelopmental disorders. We identified 3 synaptic genes (DLG2, PCDH15, and ASTN2) as risk factors for BD. Whereas gene set analysis showed that BD-associated pathways were restricted to chromatin biology, SCZ and ASD involved more extensive and similar pathways. Nevertheless, a correlation analysis of gene set results indicated weak but significant pathway similarities between BD and SCZ or ASD (r = 0.25–0.31). In SCZ and ASD, but not BD, CNVs were significantly enriched in enhancers and promoters in brain tissue. Conclusions: BD and SCZ/ASD differ in terms of CNV burden, characteristics of CNVs linked to neurodevelopmental disorders, and regulatory CNVs. On the other hand, they have shared molecular mechanisms, including chromatin biology. The BD risk genes identified here could provide insight into the pathogenesis of BD.

DOI： 10.1016/j.biopsych.2022.04.003

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

DOI： 10.1002/pcn5.36

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その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/pcn5.36

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：International Journal of Geriatric Psychiatry  

Objectives: Delirium may be divided into multiple subtypes with different pathological factors. This study aimed to focus on the delirium subtype in which delusions are conspicuous and explore its prevalence, clinical characteristics, and risk factors. Methods: The subjects were 601 delirium cases referred to the department of psychiatry over 5 years at a general hospital. The Delirium Rating Scale-Revised-98 was used to assess the delusions in patients with delirium, and the features of delusions (delusional form, object, and content) were examined. Multiple regression analysis was applied to determine whether individual factors were associated with the delusions. Results: A total of 78 patients with delirium experienced delusions (13.0%). Most were classified as delusion of reference, such as persecution or poisoning, and 84.3% of patients believed that the persecutors were medical staff members. Older age (p < 0.001), female gender (p < 0.001), and living alone (p < 0.001) were significantly associated with delusions in patients with delirium. Conclusions: The content of delusions was rooted in the distress caused by the patients' medical situation, and the features and risk factors of the delusions suggested a formal similarity with late paraphrenia and “lack-of-contact paranoia.” Psychological interventions that consider the isolation, anxiety, and fear behind delusions may be necessary in the care and treatment of these patients.

DOI： 10.1002/gps.5763

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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：Journal of Personalized Medicine  

The augmentation of clozapine with electroconvulsive therapy (ECT) has been an optimal treatment option for patients with treatment-or clozapine-resistant schizophrenia. Using data from the Research on Asian Psychotropic Prescription Patterns for Antipsychotics survey, which was the largest international psychiatry research collaboration in Asia, our study aimed to develop a machine learning algorithm-based substantial prediction model for the augmented use of clozapine with ECT in patients with schizophrenia in terms of precision medicine. A random forest model and least absolute shrinkage and selection operator (LASSO) model were used to develop a substantial prediction model for the augmented use of clozapine with ECT. Among the 3744 Asian patients with schizophrenia, those treated with a combination of clozapine and ECT were characterized by significantly greater proportions of females and inpatients, a longer duration of illness, and a greater prevalence of negative symptoms and social or occupational dysfunction than those not treated. In the random forest model, the area under the curve (AUC), which was the most preferred indicator of the prediction model, was 0.774. The overall accuracy was 0.817 (95% confidence interval, 0.793–0.839). Inpatient status was the most important variable in the substantial prediction model, followed by BMI, age, social or occupational dysfunction, persistent symptoms, illness duration > 20 years, and others. Furthermore, the AUC and overall accuracy of the LASSO model were 0.831 and 0.644 (95% CI, 0.615–0.672), respectively. Despite the subtle differences in both AUC and overall accuracy of the random forest model and LASSO model, the important variables were commonly shared by the two models. Using the machine learning algorithm, our findings allow the development of a substantial prediction model for the augmented use of clozapine with ECT in Asian patients with schizophrenia. This substantial prediction model can support further studies to develop a substantial prediction model for the augmented use of clozapine with ECT in patients with schizophrenia in a strict epidemiological context.

DOI： 10.3390/jpm12060969

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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：Nagoya Journal of Medical Science  

A number of genomic mutations that are thought to be strongly involved in the development of schizophrenia (SCZ) and autism spectrum disorder (ASD) have been identified. Abnormalities involving oligodendrocytes have been reported in SCZ, and as a related gene, oligodendrocyte lineage transcription factor 2 (OLIG2) has been reported to be strongly associated with SCZ. In this study, based on the common disease–rare variant hypothesis, target sequencing of candidate genes was performed to identify rare mutations with a high effect size and the possibility that the identified mutations may increase the risks of SCZ and ASD in the Japanese population. In this study, the exon region of OLIG2 was targeted; 370 patients with SCZ and 192 with ASD were subjected to next-generation sequencing. As a result, one rare missense mutation (A33T) was detected. We used the Sanger method to validate this missense mutation with a low frequency (<1%), and then carried out a genetic association analysis involving 3299 unrelated individuals (1447 with SCZ, 380 with ASD, and 1472 healthy controls) to clarify whether A33T was associated with SCZ or ASD. A33T was not found in either case group, and in only one control. We did not find evidence that p.A33T is involved in the onset of ASD or SCZ; however, associations with this variant need to be evaluated in larger samples to confirm our results

DOI： 10.18999/nagjms.84.2.260

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

DOI： 10.3389/fpsyt.2022.876678

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

DOI： 10.3389/fpsyt.2022.876727

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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：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：英語   出版者・発行元：Neuropsychopharmacology Reports  

Background: Coronavirus disease 2019 (COVID-19) is known to cause not only respiratory but also neuropsychiatric symptoms, which are assumed to be derived from a cytokine storm and its effects on the central nervous systems. Patients with COVID-19 who develop severe respiratory symptoms are known to show severe neuropsychiatric symptoms such as cerebrovascular disease and encephalopathy. However, the detailed clinical courses of patients with neuropsychiatric symptoms caused by mild or asymptomatic COVID-19 remain poorly understood. Here, we present a case of COVID-19 who presented with severe and prolonged neuropsychiatric symptoms subsequent to mild respiratory symptoms. Case presentation: A 55-year-old female with COVID-19 accompanied by mild respiratory symptoms showed delusion, psychomotor excitement, and poor communication ability during quarantine outside the hospital. Considering her diminished respiratory symptoms, her neuropsychiatric symptoms were initially regarded as psychogenic reactions. However, as she showed progressive disturbance of consciousness accompanied by an abnormal electroencephalogram, she was diagnosed with post-COVID-19 encephalopathy. Although her impaired consciousness and elevated cytokine level improved after steroid pulse therapy, several neuropsychiatric symptoms, including a loss of concentration, unsteadiness while walking, and fatigue, remained. Conclusions: This case suggests the importance of both recognizing that even apparently mild COVID-19-related respiratory symptoms can lead to severe and persistent neuropsychiatric symptoms, and elucidating the mechanisms, treatment, and long-term course of COVID-19-related neuropsychiatric symptoms in the future.

DOI： 10.1002/npr2.12222

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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：Journal of Personalized Medicine  

The symptom heterogeneity of schizophrenia is consistent with Wittgenstein’s analogy of a language game. From the perspective of precision medicine, this study aimed to estimate the symptom presentation and identify the psychonectome in Asian patients, using data obtained from the Research on Asian Psychotropic Prescription Patterns for Antipsychotics. We constructed a network structure of the Brief Psychiatric Rating Scale (BPRS) items in 1438 Asian patients with schizophrenia. Furthermore, all the BPRS items were considered to be an ordered categorical variable ranging in value from 1–7. Motor retardation was situated most centrally within the BPRS network structure, followed by depressive mood and unusual thought content. Contrastingly, hallucinatory behavior was situated least centrally within the network structure. Using a community detection algorithm, the BPRS items were organized into positive, negative, and general symptom clusters. Overall, DSM symptoms were not more central than non-DSM symptoms within the symptom network of Asian patients with schizophrenia. Thus, motor retardation, which results from the unmet needs associated with current antipsychotic medications for schizophrenia, may be a tailored treatment target for Asian patients with schizophrenia. Based on these findings, targeting non-dopamine systems (glutamate, γ-aminobutyric acid) may represent an effective strategy with respect to precision medicine for psychosis.

DOI： 10.3390/jpm12010033

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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：Psychiatry Investigation  

Objective Recently, rational polypharmacy approaches have been proposed, regardless of the lower risk and cost of monotherapy. Considering monotherapy as first-line treatment and polypharmacy as rational treatment, a balanced attitude toward polypharmacy is recommended. However, the high prevalence of polypharmacy led the Japanese government to establish a polypharmacy reduction policy. Based on this, the association between the policy and psychiatrists’ attitude toward polypharmacy has been under debate. Methods We developed an original questionnaire about Psychiatrists’ attitudes toward polypharmacy (PAP). We compared the PAP scores with the treatment decision-making in clinical case vignettes. Multiple regression analyses were performed to quantify associations of explanatory variables including policy factors and PAP scores. The anonymous questionnaires were administered to psychiatrists worldwide. Results The study included 347 psychiatrists from 34 countries. Decision-making toward polypharmacy was associated with high PAP scores. Multiple regression analysis revealed that low PAP scores were associated with the policy factor (β=-0.20, p=0.004). The culture in Korea was associated with high PAP scores (β=0.34, p<0.001), whereas the culture in India and Nepal were associated with low scores (β=-0.15, p=0.01, and β=-0.17, p=0.006, respectively). Conclusion Policy on polypharmacy may influence psychiatrists’ decision-making. Thus, policies considering rational polypharmacy should be established.

DOI： 10.30773/pi.2021.0169

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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：Human Psychopharmacology  

Background: Various factors affecting the development of delirium have been identified. However, the associations between the severity of delirium and potentially related factors have not been adequately investigated. The aim of the present study was to explore factors associated with the severity of delirium and to identify the reversible contributing factors. Methods: A total of 577 patients with delirium referred to the Department of Psychiatry during the 5 years from May 2015 to April 2020 at a general hospital were included. The Delirium Rating Scale-revised-98 (DRS-R-98) was used to measure the severity of delirium. Multiple regression analysis was used to determine whether individual factors were associated with the severity of delirium. Results: Intensive care unit admission (p = 0.003), use of benzodiazepines (p = 0.01), dementia (p = 0.02), and older age (p = 0.045) were all positively associated the severity of delirium, while use of β-blockers (p = 0.001) was negatively associated with the severity of delirium. Conclusions: Reversible contributing factors, that is use of benzodiazepines, should be avoided as much as possible, especially in elderly patients or patients with dementia or patients who need critical care in ICU. Reducing the dose of benzodiazepines or switching them to other drugs should be a priority.

DOI： 10.1002/hup.2787

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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：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：英語   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：英語   掲載種別：研究論文（学術雑誌）   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：英語   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：英語   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：英語   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：英語   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：英語   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：英語   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：英語   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：英語   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：英語   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：英語   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：英語   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：英語   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：英語   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：英語   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：英語   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：英語   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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PubMed

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：英語   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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PubMed

記述言語：英語   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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PubMed

記述言語：英語   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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PubMed

記述言語：英語   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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PubMed

記述言語：英語   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

記述言語：英語   出版者・発行元：Translational Psychiatry  

Reticulon 4 receptor (RTN4R) plays an essential role in regulating axonal regeneration and plasticity in the central nervous system through the activation of rho kinase, and is located within chromosome 22q11.2, a region that is known to be a hotspot for schizophrenia (SCZ) and autism spectrum disorder (ASD). Recently, rare variants such as copy-number variants and single-nucleotide variants have been a focus of research because of their large effect size associated with increased susceptibility to SCZ and ASD and the possibility of elucidating the pathophysiology of mental disorder through functional analysis of the discovered rare variants. To discover rare variants with large effect size and to evaluate their role in the etiopathophysiology of SCZ and ASD, we sequenced the RTN4R coding exons with a sample comprising 370 SCZ and 192 ASD patients, and association analysis using a large number of unrelated individuals (1716 SCZ, 382 ASD and 4009 controls). Through this mutation screening, we discovered four rare (minor allele frequency o1%) missense mutations (R68H, D259N, R292H and V363M) of RTN4R. Among these discovered rare mutations, R292H was found to be significantly associated with SCZ (P = 0.048). Furthermore, in vitro functional assays showed that the R292H mutation affected the formation of growth cones. This study strengthens the evidence for association between rare variants within RTN4R and SCZ, and may shed light on the molecular mechanisms underlying the neurodevelopmental disorder.

DOI： 10.1038/tp.2017.170

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その他リンク： http://www.nature.com/articles/tp2017170

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

DOI： 10.1093/ijnp/pyx020

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PubMed

記述言語：英語   出版者・発行元：Schizophrenia Research  

DOI： 10.1016/j.schres.2016.08.023

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PubMed

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

その他リンク： https://www.amazon.co.jp/DIEPSS%E3%82%92%E4%BD%BF%E3%81%84%E3%81%93%E3%81%AA%E3%81%99-%E6%94%B9%E8%A8%82%E7%89%88-%E8%96%AC%E5%8E%9F%E6%80%A7%E9%8C%90%E4%BD%93%E5%A4%96%E8%B7%AF%E7%97%87%E7%8A%B6%E3%81%AE%E8%A9%95%E4%BE%A1%E3%81%A8%E8%A8%BA%E6%96%AD-DIEPSS%E3%81%AE%E8%A7%A3%E8%AA%AC%E3%81%A8%E5%88%A9%E7%94%A8%E3%81%AE%E6%89%8B%E5%BC%95%E3%81%8D-%E7%A8%B2%E7%94%B0-%E4%BF%8A%E4%B9%9F/dp/4791108027/ref=sr_1_1?s=books&ie=UTF8&qid=1490582606&sr=1-1&keywords=DIEPSS%C3%A3%C2%82%C2%92%C3%A4%C2%BD%C2%BF%C3%A3%C2%81%C2%84%C3%A3%C2%81%C2%93%C3%A3%C2%81%C2%AA%C3%A3%C2%81%C2%99&language=ja_JP

記述言語：英語 著書種別：学術書

記述言語：日本語

CiNii Books

記述言語：日本語

CiNii Books

記述言語：日本語

CiNii Books

記述言語：日本語   出版者・発行元：星和書店  

記述言語：日本語   出版者・発行元：星和書店  

CiNii Books

その他リンク： http://search.jamas.or.jp/link/ui/2017402712

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

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   出版者・発行元：星和書店  

CiNii Books

記述言語：英語   掲載種別：速報，短報，研究ノート等（学術雑誌）  

記述言語：日本語   出版者・発行元：星和書店  

CiNii Books

記述言語：日本語   掲載種別：記事・総説・解説・論説等（学術雑誌）