Publications by authors named "Naoki Hashimoto"

144 Publications

Lipid and Energy Metabolism of the Gut Microbiota Is Associated with the Response to Probiotic Strain for Anxiety and Depressive Symptoms in Schizophrenia.

J Pers Med 2021 Sep 30;11(10). Epub 2021 Sep 30.

Division of Health Care Research, Center for Public Health Sciences, National Cancer Center Japan, Tokyo 104-0045, Japan.

A recent meta-analysis found that probiotics have moderate-to-large beneficial effects on depressive symptoms in patients with psychiatric disorders. However, it remains unclear how the baseline gut microbiota before probiotic administration influences the host's response to probiotics. Therefore, we aimed to determine whether the predicted functional profile of the gut microbiota influences the effectiveness of probiotic treatment in patients with schizophrenia. A total of 29 patients with schizophrenia consumed A-1 (synonym MCC1274) for 4 weeks. We considered patients who showed a 25% or more reduction in the Hospital Anxiety and Depression Scale total score at 4 weeks from baseline to be "responders" and those who did not to be "non-responders". We predicted the gut microbial functional genes based on 16S rRNA gene sequences and applied the linear discriminant analysis effect size method to determine the gut microbial functional genes most likely to explain the differences between responders and non-responders at baseline. The results showed that lipid and energy metabolism was elevated at baseline in responders ( = 12) compared to non-responders ( = 17). These findings highlight the importance of assessing the gut microbial functional genes at baseline before probiotic therapy initiation in patients with psychiatric disorders.
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http://dx.doi.org/10.3390/jpm11100987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8539730PMC
September 2021

The type rather than the daily dose or number of antipsychotics affects the incidence of hyperglycemic progression.

Prog Neuropsychopharmacol Biol Psychiatry 2021 Oct 9;113:110453. Epub 2021 Oct 9.

Department of Psychiatry, Hokkaido University Graduate School of Medicine, North 15, West 7, Sapporo 060-8638, Japan. Electronic address:

There have been concerns that antipsychotics increase the incidence of hyperglycemic progression. Many factors have been suggested to contribute to the risk of antipsychotic-induced hyperglycemic progression, including the type, daily dose, and number of antipsychotics; however, few studies have examined these relationships. This study aimed to examine the affect of antipsychotic treatment-associated factors on hyperglycemic progression, after adjustment for the affect of background factors suggested to be associated with hyperglycemic progression. This was a nationwide, multicenter, prospective cohort study examining the incidence of hyperglycemic progression during a 12 mo period following the initiation of newly prescribed antipsychotic medication. Demographic data, medication history, and blood test values were collected from 631 study participants with normal blood glucose levels at baseline for 12 mo. The primary endpoint (incidence of hyperglycemic progression) was defined as progression from normal to prediabetic or probable diabetic status, and was evaluated based on the Japanese monitoring guidance in patients with schizophrenia. To further examine the affect of antipsychotics on glucose metabolism over time, we examined changes in HbA1c levels 3, 6, and 12 mo after the initiation of treatment with each antipsychotic. We found that treatment with zotepine and clozapine was associated with a significantly high incidence of hyperglycemic progression. Furthermore, changes in HbA1c levels 6 mo after the initiation of zotepine treatment were significantly higher than those following blonanserin and haloperidol treatments. In contrast, there was no significant difference in the change in total cholesterol, triglycerides, HDL cholesterol, and BMI during the same period. Moreover, the "daily dose" and "number" of antipsychotics did not show an association with the incidence of hyperglycemic progression. However, in a post hoc analysis in which the antipsychotics were divided into two groups according to the strength of blockade of H, M, M, and 5-HT receptors, the incidence of hyperglycemic progression was higher in the medium- and high-daily dose groups than in the low-daily dose group in the antipsychotic group with strong blockade of these receptors. Our study indicated that the type of antipsychotic had a greater affect on the incidence of hyperglycemic progression than the daily dose of antipsychotics or their number. Among these, zotepine was most likely to increase the incidence of hyperglycemic progression, suggesting the need for caution when these antipsychotics are prescribed.
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http://dx.doi.org/10.1016/j.pnpbp.2021.110453DOI Listing
October 2021

Study Protocol: The Evaluation Study for Social Cognition Measures in Japan (ESCoM).

J Pers Med 2021 Jul 16;11(7). Epub 2021 Jul 16.

Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.

In schizophrenia, social cognitive impairment is considered one of the greatest obstacles to social participation. Although numerous measures have been developed to assess social cognition, only a limited number of them have become available in Japan. We are therefore planning this evaluation study for social cognition measures in Japan (ESCoM) to confirm their psychometric characteristics and to promote research focused on social cognition. Participants in the cross-sectional observational study will be 140 patients with schizophrenia recruited from three Japanese facilities and 70 healthy individuals. In our primary analysis, we will calculate several psychometric indicators with a focus on whether they can independently predict social functioning. In secondary analyses, we will assess the reliability and validity of the Japanese translations of each measure and conduct an exploratory investigation of patient background, psychiatric symptoms, defeatist performance belief, and gut microbiota as determinants of social cognition. The protocol for this study is registered in UMIN-CTR, unique ID UMIN000043777.
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http://dx.doi.org/10.3390/jpm11070667DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8305726PMC
July 2021

Characteristics of discharge prescriptions for patients with schizophrenia or major depressive disorder: Real-world evidence from the Effectiveness of Guidelines for Dissemination and Education (EGUIDE) psychiatric treatment project.

Asian J Psychiatr 2021 Sep 15;63:102744. Epub 2021 Jul 15.

Department of Pathology of Mental Diseases, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, Japan.

Background: Monopharmacy with antipsychotics and antidepressants is the first-line treatment for schizophrenia and major depressive disorder (MDD) in most clinical guidelines, while polypharmacy with psychotropic agents in the treatment of schizophrenia is common in clinical practice. There are no detailed data on the prescription patterns for inpatients with mental illness with reliable diagnoses made by treating psychiatrists.

Methods: We gathered prescription data at discharge from 2177 patients with schizophrenia and 1238 patients with MDD from October 2016 to March 2018.

Results: The patients with schizophrenia aged between 60 and 79 were prescribed lower doses of antipsychotics and hypnotics/anxiolytics than those aged between 40 and 59. There were significant differences between the prescription rate of antipsychotics in the patients with schizophrenia and that of antidepressants in the patients with MDD. The frequency of concomitant drugs such as anti-Parkinson drugs, anxiolytics/hypnotics and mood stabilizers in the subjects with schizophrenia prescribed antipsychotic polypharmacy was significantly higher than that with monotherapy. For the patients with schizophrenia, olanzapine, risperidone, aripiprazole, quetiapine, and blonanserin were the five most prescribed antipsychotics. For the patients with MDD, mirtazapine, duloxetine, escitalopram, trazodone and sertraline were the five most prescribed antidepressants.

Conclusions: Our results showed the use of high doses of antipsychotics, high percentages of antipsychotic polypharmacy and concurrent use of hypnotics/anxiolytics in patients with schizophrenia. Notably, these data were collected before intensive instruction regarding the guidelines; therefore, we need to assess the change in the prescription pattern post guideline instruction.
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http://dx.doi.org/10.1016/j.ajp.2021.102744DOI Listing
September 2021

Pharmacological treatment algorithms for the acute phase, agitation, and maintenance phase of first-episode schizophrenia: Japanese Society of Clinical Neuropsychopharmacology treatment algorithms.

Hum Psychopharmacol 2021 Jul 9:e2804. Epub 2021 Jul 9.

Department of Psychiatry, School of Medicine, Dokkyo Medical University, Tochigi, Japan.

Objective: There are only a few treatment algorithms for first-episode schizophrenia. Moreover, all the algorithms apply to acute treatment, but not maintenance treatment. Therefore, we aimed to develop acute and maintenance treatment algorithms for first-episode schizophrenia.

Methods: The algorithm committee of the Japanese Society of Clinical Neuropsychopharmacology developed pharmacological treatment algorithms for the acute phase, agitation, and maintenance phase of first-episode schizophrenia.

Results: The acute treatment algorithm focuses on drug-naïve patients with first-episode schizophrenia who are not old or very agitated and recommends first-line treatment with aripiprazole, second- or third-line treatment with risperidone/paliperidone or olanzapine, and fourth-line treatment with clozapine. Long-acting injection of the current antipsychotic agent can be used for poor medication adherence or based on patient preference. The agitation treatment algorithm recommends first-line treatment with lorazepam and second- or third-line treatment with quetiapine or levomepromazine and clearly instructs that the medication used for agitation should be reduced and then discontinued after remission of agitation. The maintenance treatment algorithm recommends the gradual reduction of antipsychotics to the minimum effective dose after remission of positive symptoms.

Conclusions: We hope that our unique algorithms will be used broadly and will contribute to minimizing patients' burden related to antipsychotic treatment.
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http://dx.doi.org/10.1002/hup.2804DOI Listing
July 2021

Hydrogen spillover-driven synthesis of high-entropy alloy nanoparticles as a robust catalyst for CO hydrogenation.

Nat Commun 2021 Jun 23;12(1):3884. Epub 2021 Jun 23.

Division of Materials and Manufacturing Science, Graduate School of Engineering, Osaka University, Osaka, Japan.

High-entropy alloys (HEAs) have been intensively pursued as potentially advanced materials because of their exceptional properties. However, the facile fabrication of nanometer-sized HEAs over conventional catalyst supports remains challenging, and the design of rational synthetic protocols would permit the development of innovative catalysts with a wide range of potential compositions. Herein, we demonstrate that titanium dioxide (TiO) is a promising platform for the low-temperature synthesis of supported CoNiCuRuPd HEA nanoparticles (NPs) at 400 °C. This process is driven by the pronounced hydrogen spillover effect on TiO in conjunction with coupled proton/electron transfer. The CoNiCuRuPd HEA NPs on TiO produced in this work were found to be both active and extremely durable during the CO hydrogenation reaction. Characterization by means of various in situ techniques and theoretical calculations elucidated that cocktail effect and sluggish diffusion originating from the synergistic effect obtained by this combination of elements.
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http://dx.doi.org/10.1038/s41467-021-24228-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222268PMC
June 2021

Comprehensive assessment of left atrial and ventricular remodeling in paroxysmal atrial fibrillation by the cardiovascular magnetic resonance myocardial extracellular volume fraction and feature tracking strain.

Sci Rep 2021 05 25;11(1):10941. Epub 2021 May 25.

Department of Cardiovascular Medicine, Nihon University Graduate School, 30-1 Oyaguchi kamimachi, Itabashi, Tokyo, 173-8610, Japan.

Atrial fibrillation (AF) is a progressive disease that starts with structural or functional changes in the left atrium and left ventricle, and evolves from paroxysmal toward sustained forms. Early detection of structural or functional changes in the left atrium and left ventricle in the paroxysmal stage could be useful for identifying a higher risk of progression to persistent AF and future cardio-cerebrovascular events. The aim of this study was to test the hypothesis that the feature tracking (FT) left atrial (LA) strain and left ventricular (LV) extracellular volume fraction (ECV) derived from cardiovascular magnetic resonance (CMR) could detect early changes in remodeling of the left atrium and ventricle in the paroxysmal AF (PAF) stage. The participants were comprised of 106 PAF patients (age, 66.1 ± 10.7 years; 66% male) who underwent clinical CMR before pulmonary vein isolation and 20 control subjects (age, 68.3 ± 8.6 years; 55% male). The CMR-FT LA strain/phasic function and LV-ECV were compared between the PAF and control groups. The total and passive LA empty fraction (LAEF) and LA strain (corresponding to LA reservoir and conduit function) were decreased in the PAF group as compared to the control group. However, active LAEF (corresponding to the LA booster pump function) did not differ significantly between the PAF group (33.9 ± 10.9%) and control group (37.9 ± 13.3%, p = 0.15), while the active LA strain (corresponding to the LA booster pump function) was significantly decreased in the PAF group (11.4 ± 4.3 vs. 15.2 ± 5.6%, p = 0.002). The LV-ECV was significantly greater in the PAF group (28.7 ± 2.8%) than control group (26.6 ± 2.0%, p = 0.002). In the PAF group, the LV-ECV correlated significantly with the E/e' and LA volume index. Regarding the LA strain, correlations were seen between the LV-ECV and both the reservoir function and conduit function. CMR-FT LA strain in combination with the LV-ECV in a single clinical study offers a potential imaging marker that identifies LA/LV remodeling including subtle LA booster pump dysfunction undetectable by the conventional booster pump LAEF in the PAF stage.
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http://dx.doi.org/10.1038/s41598-021-90117-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149643PMC
May 2021

Comprehensive assessment of left atrial and ventricular remodeling in paroxysmal atrial fibrillation by the cardiovascular magnetic resonance myocardial extracellular volume fraction and feature tracking strain.

Sci Rep 2021 05 25;11(1):10941. Epub 2021 May 25.

Department of Cardiovascular Medicine, Nihon University Graduate School, 30-1 Oyaguchi kamimachi, Itabashi, Tokyo, 173-8610, Japan.

Atrial fibrillation (AF) is a progressive disease that starts with structural or functional changes in the left atrium and left ventricle, and evolves from paroxysmal toward sustained forms. Early detection of structural or functional changes in the left atrium and left ventricle in the paroxysmal stage could be useful for identifying a higher risk of progression to persistent AF and future cardio-cerebrovascular events. The aim of this study was to test the hypothesis that the feature tracking (FT) left atrial (LA) strain and left ventricular (LV) extracellular volume fraction (ECV) derived from cardiovascular magnetic resonance (CMR) could detect early changes in remodeling of the left atrium and ventricle in the paroxysmal AF (PAF) stage. The participants were comprised of 106 PAF patients (age, 66.1 ± 10.7 years; 66% male) who underwent clinical CMR before pulmonary vein isolation and 20 control subjects (age, 68.3 ± 8.6 years; 55% male). The CMR-FT LA strain/phasic function and LV-ECV were compared between the PAF and control groups. The total and passive LA empty fraction (LAEF) and LA strain (corresponding to LA reservoir and conduit function) were decreased in the PAF group as compared to the control group. However, active LAEF (corresponding to the LA booster pump function) did not differ significantly between the PAF group (33.9 ± 10.9%) and control group (37.9 ± 13.3%, p = 0.15), while the active LA strain (corresponding to the LA booster pump function) was significantly decreased in the PAF group (11.4 ± 4.3 vs. 15.2 ± 5.6%, p = 0.002). The LV-ECV was significantly greater in the PAF group (28.7 ± 2.8%) than control group (26.6 ± 2.0%, p = 0.002). In the PAF group, the LV-ECV correlated significantly with the E/e' and LA volume index. Regarding the LA strain, correlations were seen between the LV-ECV and both the reservoir function and conduit function. CMR-FT LA strain in combination with the LV-ECV in a single clinical study offers a potential imaging marker that identifies LA/LV remodeling including subtle LA booster pump dysfunction undetectable by the conventional booster pump LAEF in the PAF stage.
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http://dx.doi.org/10.1038/s41598-021-90117-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149643PMC
May 2021

Evaluation of Social Cognition Measures for Japanese Patients with Schizophrenia Using an Expert Panel and Modified Delphi Method.

J Pers Med 2021 Apr 6;11(4). Epub 2021 Apr 6.

Department of Neuropsychiatry, Toho University Faculty of Medicine, Tokyo 143-8541, Japan.

Social cognition is strongly linked to social functioning outcomes, making it a promising treatment target. Because social cognition measures tend to be sensitive to linguistic and cultural differences, existing measures should be evaluated based on their relevance for Japanese populations. We aimed to establish an expert consensus on the use of social cognition measures in Japanese populations to provide grounds for clinical use and future treatment development. We assembled a panel of experts in the fields of schizophrenia, social psychology, social neuroscience, and developmental disorders. The panel engaged in a modified Delphi process to (1) affirm expert consensus on the definition of social cognition and its constituent domains, (2) determine criteria to evaluate measures, and (3) identify measures appropriate for Japanese patients with a view toward future quantitative research. Through two online voting rounds and two online video conferences, the panel agreed upon a definition and four-domain framework for social cognition consistent with recent literature. Evaluation criteria for measures included feasibility and tolerability, reliability, clinical effectiveness, validity, and international comparability. The panel finally identified nine promising measures, including one task originally developed in Japan. In conclusion, we established an expert consensus on key discussion points in social cognition and arrived at an expert-selected set of measures. We hope that this work facilitates the use of these measures in Japanese clinical scenarios. We plan to further examine these measures in a psychometric evaluation study.
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http://dx.doi.org/10.3390/jpm11040275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067370PMC
April 2021

Quantitative Resting State Electroencephalography in Patients with Schizophrenia Spectrum Disorders Treated with Strict Monotherapy Using Atypical Antipsychotics.

Clin Psychopharmacol Neurosci 2021 May;19(2):313-322

Department of Psychiatry, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.

Objective: The effect of antipsychotic drugs on quantitative electroencephalography (EEG) has been mainly examined by the administration of a single test dose or among patients using combinations of other psychotropic drugs. We therefore investigated the effects of strict monotherapy with antipsychotic drugs on quantitative EEG among schizophrenia patients.

Methods: Data from 2,364 medical reports with EEG results from psychiatric patients admitted to the Hokkaido University Hospital were used. We extracted EEG records of patients who were diagnosed with schizophrenia spectrum disorders and who were either undergoing strict antipsychotic monotherapy or were completely free of psychotropic drugs. The spectral power was compared between drug-free patients and patients using antipsychotic drugs. We also performed multiple regression analysis to evaluate the relationship between spectral power and the chlorpromazine equivalent daily dose of antipsychotics in all the patients.

Results: We included 31 monotherapy and 20 drug-free patients. Compared with drug-free patients, patients receiving antipsychotic drugs demonstrated significant increases in theta, alpha and beta power. When patients taking different types of antipsychotics were compared with drug-free patients, we found no significant change in any spectrum power for the aripiprazole or blonanserin groups. Patients taking risperidone demonstrated significant increases in alpha and beta power. Patients taking clozapine and olanzapine demonstrated significant slow wave increases. Multiple regression analysis revealed that the chlorpromazine equivalent dose was positively associated with theta power.

Conclusion: Use of any antipsychotic drug by patients was associated with a dose-dependent increase in theta power. However, each type of antipsychotic demonstrated different spectral power changes.
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http://dx.doi.org/10.9758/cpn.2021.19.2.313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8077067PMC
May 2021

How the Morphology of NiO-Decorated CeO Nanostructures Affects Catalytic Properties in CO Methanation.

Langmuir 2021 May 21;37(17):5376-5384. Epub 2021 Apr 21.

Division of Materials and Manufacturing Science, Graduate School of Engineering, Osaka University, 2-1 Yamada-oka, Suita, Osaka 565-0871, Japan.

Effects of morphology and exposed crystal planes of NiO-decorated CeO (NiCeO) nanostructured catalysts on activity during CO methanation were examined, using nanorod (NR), nanocube (NC), and nanooctahedron (NO) structures. The NiCeO nanorods (NiCeO-NR) showed superior activity to NiCeO-NC and NiCeO-NO along with excellent selectivity for CH. This material also demonstrated exceptional durability, with no significant loss of catalytic activity or structural change after use. Comprehensive physicochemical characterization as well as density functional theory calculations determined that the high performance of the NiCeO-NR was closely related to the large quantity of surface oxygen vacancies and the high degree of reversibility associated with the Ce ↔ Ce redox cycle of the support. These effects originate from the enhanced reactivity of oxygen atoms on the (110) surfaces of the oxide compared with the (100) and (111) surfaces. This information is expected to assist in the rational design of practical catalysts for the activation of CO molecules and other important transformations.
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http://dx.doi.org/10.1021/acs.langmuir.1c00546DOI Listing
May 2021

[Two Cases in Which Simultaneous Laparoscopic Surgery and Breast Cancer Surgery Using a Head-Mounted Monitor Were Useful].

Gan To Kagaku Ryoho 2021 Mar;48(3):403-406

Division of Gastroenterological Surgery, Clinical Oncology Center, Aomori Prefectural Central Hospital.

Herein, we report on how we were able to reduce the operation time by simultaneously performing laparoscopic surgery and breast cancer surgery using a head-mounted monitor(HMS-3000MT, Sony corporation). Case 1: 60s, female. A 5.5 cm leiomyoma was found in the central thoracic esophagus, and a 1 cm breast cancer was found in the C region of the left mammary gland. Subtotal esophagectomy with right thoracotomy and laparoscopy and a left partial mastectomy were performed. For the abdominal surgery, HMS-3000MT was used under hand-assisted laparoscopy, and a left partial mastectomy was performed concurrently. Operation time was 367 minutes(simultaneous surgery for 56 minutes). Esophagus: leiomyoma, 50×45 mm; and mammary gland: 16×15 mm, pTis(DCIS), pN0(sn), cM0, and pStage 0. Case 2: 70s, female. A 3 cm sized GIST was found on the posterior wall of the middle gastric body, and a breast cancer of 1.3 cm was also found in the B region of the right mammary gland. Using HMS-3000MT, laparoscopic local resection of the stomach and right total glandectomy were performed concurrently. Operation time was 114 minutes(simultaneous surgery for 58 minutes). Stomach: GIST, 25×22 mm, and modified Flecher classification low risk; and mammary gland: invasive ductal carcinoma, 15×15 mm, pT1c, pN0(sn), cM0, and pStage Ⅰ. Conclusion: In 2 fields of surgery, simultaneous surgery using HMS-3000MT was considered to be a useful method to shorten the operation time.
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March 2021

Self-Assembled 3D Actuator Using the Resilience of an Elastomeric Material.

Front Robot AI 2019 15;6:152. Epub 2020 Jan 15.

Department of Applied Physics, Waseda University, Tokyo, Japan.

Self-folding technologies have been studied by many researchers for applications to various engineering fields. Most of the self-folding methods that use the physical properties of materials require complex preparation, and usually take time to complete. In order to solve these problems, we focus on the elasticity of a material, and propose a model for forming a 3D structure using its characteristics. Our proposed model achieves high-speed and high-precision self-folding with a simple structure, by attaching rigid frames to a stretchable elastomer. The self-folded structure is applied to introduce a self-assembled actuator by exploiting a dielectric elastomer actuator (DEA). We develop the self-assembled actuator driven with the voltage application by attaching stretchable electrodes on the both side of the elastomer. We attempt several experiments to investigate the basic characteristics of the actuator. We also propose an application of the self-assembled actuator as a gripper based on the experimental results. The gripper has three joints with the angle of 120°, and successfully grabs objects by switching the voltage.
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http://dx.doi.org/10.3389/frobt.2019.00152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806082PMC
January 2020

[A Case of Laparoscopic Distal Gastrectomy for Gastric Cancer with an Adachi Type Ⅵ Group 24 Vascular Anomaly].

Gan To Kagaku Ryoho 2020 Dec;47(13):2162-2164

Dept. of Surgery, Clinical Oncology Center, Aomori Prefectural Central Hospital.

We report a case of successful laparoscopic distal gastrectomy for gastric cancer with an Adachi type Ⅵ group 24 vascular anomaly. A male in his 60s exhibited a type 0-Ⅱa plus Ⅱc lesion at the lesser curvature of the gastric angle by esophagogastroduodenoscopy and was diagnosed with tub2. He was referred to us for surgical treatment. The clinical diagnosis was cT1bN0M0, and cStage Ⅰ. Preoperative multidetector-row computed tomography(MDCT)showed an Adachi type Ⅵ group 24 vascular anomaly. At laparoscopic surgery, we dissected No. 8a lymph nodes with exposure of the surface of the portal vein because the common hepatic artery was absent. The left gastric artery and splenic artery formed a common trunk. As there are various kinds of vascular anomalies of the celiac artery branch, we must understand the arterial running pattern prior to gastric surgery. This technique is more useful in laparoscopic surgeries where tactile sensation is limited. To prevent perioperative and postoperative complications, we must recognize the anomaly pattern prior to surgery using MDCT.
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December 2020

Apathy in Alzheimer's Disease Correlates with the Dopamine Transporter Level in the Caudate Nuclei.

Dement Geriatr Cogn Dis Extra 2020 May-Aug;10(2):86-93. Epub 2020 Sep 9.

Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo, Japan.

Introduction: Apathy is a common neuropsychiatric symptom in patients with Alzheimer's disease (AD). The striatal binding potential (BP) of I-FP-CIT (-δ-fluoropropyl-2β-carbomethoxy-3β-[4-iodophenyl]tropane) single-photon emission computed tomography (SPECT) is correlated with the degree of apathy in patients with Parkinson's disease (PD) and dementia with Lewy bodies (DLB). This study aimed to determine if dopaminergic activity in the basal ganglia is associated with the development of apathy in AD.

Methods: Nineteen subjects with AD were included and underwent I-FP-CIT-SPECT. Patients with other types of dementia as a comorbidity, those taking antidepressants, and those with overt parkinsonism were excluded. Apathy was assessed using the Apathy Evaluation Scale Informant-Japanese version (AES-I-J). SPECT images were overlaid with images in striatal regions of interest (ROIs), and the SPECT values in these regions were counted. The relationship between BP values and AES-I-J scores was investigated using Spearman's rank correlation coefficient.

Results: Significant inverse correlations were observed between BP values and AES-I-J scores in the left caudate nucleus and there was a marginally significant inverse correlation in the right caudate nucleus.

Conclusion: The pathological basis of apathy might be the impairment of the dopaminergic nervous system. Further studies on more subjects with AD, healthy controls, and patients with PD and DLB are needed.
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http://dx.doi.org/10.1159/000509278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7548940PMC
September 2020

Association Between -Desmethylclozapine and Clozapine-Induced Sialorrhea: Involvement of Increased Nocturnal Salivary Secretion via Muscarinic Receptors by -Desmethylclozapine.

J Pharmacol Exp Ther 2020 11 29;375(2):376-384. Epub 2020 Aug 29.

Laboratory of Clinical Pharmaceutics and Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences (S.I., M.K., H.M., K.N., A.F., K.I.) and Education Research Center for Clinical Pharmacy, Faculty of Pharmaceutical Sciences (M.K.), Hokkaido University, Sapporo, Japan; Department of Pharmacy, Hokkaido University Hospital, Sapporo, Japan (S.I.); Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo, Japan (N.H., I.K.); and Department of Pharmacology, School of Dentistry, Health Sciences University of Hokkaido, Sapporo, Japan (A.T.).

Clozapine-induced sialorrhea (CIS) is a common side effect of clozapine. There is no established standard treatment of CIS since the underlying mechanism remains unknown. This study aimed to elucidate the mechanisms involved in CIS. In our clinical study, a prospective observational study evaluated the association between serum and saliva concentrations of clozapine or its metabolites and Drooling Severity and Frequency Scale (DSFS) score. In our in vivo study, we first developed a new CIS animal model; subsequently, we measured salivary secretion and concentrations of clozapine or its metabolites in the animal model. In our in vitro study, we measured the calcium ion (Ca) response to evaluate the effect of clozapine or its metabolites on human salivary gland cell line (HSY cells) and then examined whether their effect was inhibited by atropine. In our clinical study, serum and saliva -desmethylclozapine concentrations were significantly correlated with nocturnal DSFS score. In our in vivo study, daily single oral administration of 100 mg/kg clozapine for 7 days significantly increased salivary secretion in rats. Furthermore, -desmethylclozapine concentrations in serum and submandibular glands of the rats were higher than clozapine concentrations. In our in vitro study, -desmethylclozapine only elicited an increase in the intracellular Ca in HSY cells. -desmethylclozapine-induced Ca responses were inhibited by atropine. These results suggest that -desmethylclozapine is implicated in CIS by increasing nocturnal salivation via the muscarinic receptors. Moreover, our developed animal model that reflects CIS in clinical condition plays a key role as a bridge between basic and clinical research. SIGNIFICANCE STATEMENT: Clozapine-induced sialorrhea (CIS) is a severe and frequent adverse reaction, but the mechanism underlying CIS is less well understood. This paper reports that -desmethylclozapine, a metabolite of clozapine, is implicated in CIS by increasing nocturnal salivation via the muscarinic receptors and that oral administration of clozapine at 100 mg/kg once daily for 7 days to rat is the optimum method for establishing the new animal model reflecting the clinical scenario of CIS.
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http://dx.doi.org/10.1124/jpet.120.000164DOI Listing
November 2020

Prescription patterns in patients with schizophrenia in Japan: First-quality indicator data from the survey of "Effectiveness of Guidelines for Dissemination and Education in psychiatric treatment (EGUIDE)" project.

Neuropsychopharmacol Rep 2020 09 30;40(3):281-286. Epub 2020 Jun 30.

Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo, Japan.

Background: Guideline for Pharmacological Therapy for Schizophrenia was published by the Japanese Society of Neuropsychopharmacology in 2015. "Effectiveness of Guidelines for Dissemination and Education in psychiatric treatment (EGUIDE)" project aimed to standardize medical practice using quality indicators (QIs) as indices to evaluate the quality of medical practice. In this study, we have reported the quality indicator values of prescription before the beginning of the guideline lectures in the EGUIDE project to ascertain the baseline status of treating patients with schizophrenia.

Methods: A cross-sectional, retrospective case record survey was conducted, involving 1164 patients with schizophrenia at the time of discharge. We checked all types and dosage of psychotropic drugs.

Results: Forty-three percent of patients had antipsychotic polypharmacy, and substantial concomitant medication was observed (antidepressants; 8%, mood stabilizers: 37%, anxiolytics or hypnotics: 68%).

Conclusions: In the results obtained in this study, we plant to report changes in the effectiveness of education in the EGUIDE project near the future.
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http://dx.doi.org/10.1002/npr2.12122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722678PMC
September 2020

Maternal cerebellar gray matter volume is associated with daughters' psychotic experience.

Psychiatry Clin Neurosci 2020 Jul 11;74(7):392-397. Epub 2020 May 11.

Brain Imaging Research Center, University of Connecticut, Storrs, USA.

Aim: A substantial portion of children and adolescents show subthreshold psychotic symptoms called psychotic experience (PE). Because PE shares its biological and environmental risk factors with psychotic spectrum disorders, parental neuroanatomical variation could reflect a heritable biological underpinning of PE that may predict an offspring's PE.

Methods: A total of 94 participants from 35 families without a diagnosis of major neuropsychiatric disorders were examined, including 14 mother-daughter, 17 mother-son, 12 father-daughter, and 16 father-son dyads. An offspring's PE was assessed with the Atypicality subscale of the Behavior Assessment System for Children - 2nd Edition, Self-Report of Personality form (BASCaty). We examined correlations between voxel-by-voxel parental gray matter volume and their offspring's BASCaty score.

Results: Maternal cerebellar gray matter volume using voxel-based morphometry was positively correlated with their daughters' BASCaty scores. The findings were significant in a more robust approach using cerebellum-specific normalization known. We did not find significant correlation between paternal gray matter volume and BASCaty scores or between offspring gray matter volumes and their BASCaty scores.

Conclusion: Expanding upon parent-of-origin effects in psychosis, maternal neuroanatomical variation was associated with daughters' PE. The nature of this sex-specific intergenerational effect is unknown, but maternally transmitted genes may relate cerebellum development to PE pathogenesis.
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http://dx.doi.org/10.1111/pcn.13011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7424852PMC
July 2020

Microstructural Alterations in Bipolar and Major Depressive Disorders: A Diffusion Kurtosis Imaging Study.

J Magn Reson Imaging 2020 10 23;52(4):1187-1196. Epub 2020 Apr 23.

Department of Biomarker Imaging Science, Graduate School of Medical Science and Engineering, Hokkaido University, Sapporo, Japan.

Background: Identifying structural and functional abnormalities in bipolar (BD) and major depressive disorders (MDD) is important for understanding biological processes.

Hypothesis: Diffusion kurtosis imaging (DKI) may be able to detect the brain's microstructural alterations in BD and MDD and any differences between the two.

Study Type: Prospective.

Subjects: In all, 16 BD patients, 19 MDD patients, and 20 age- and gender-matched healthy volunteers.

Field Strength/sequence: DKI at 3.0T.

Assessment: The major DKI indices of the brain were compared voxel-by-voxel among the three groups. Significantly different voxels were tested for correlation with clinical variables (ie, Young Mania Rating Scale [YMRS], 17-item Hamilton Depression Rating Scale [17-HDRS], Montgomery-Åsberg Depression Rating Scale, total disease duration, duration of current episode, and the number of past manic/depressive episodes). The performance of the DKI indices in identifying microstructural alterations was estimated.

Statistical Tests: One-way analysis of variance (ANOVA) was used for group comparison of DKI indices. The performance of these indices in detecting microstructural alterations was determined by receiver operating characteristic (ROC) analysis. Pearson's product-moment correlation analyses were used to test the correlations of these indices with clinical variables.

Results: DKI revealed widespread microstructural alterations across the brain in each disorder (P < 0.05). Some were significantly different between the two disorders. Mean kurtosis (MK) in the gray matter of the right inferior parietal lobe was able to distinguish BD and MDD with an accuracy of 0.906. A strong correlation was revealed between MK in that region and YMRS in BD patients (r = -0.641, corrected P = 0.042) or 17-HDRS in MDD patients (r = -0.613, corrected P = 0.030). There were also strong correlations between a few other DKI indices and disease duration (r = -0.676 or 0.626, corrected P < 0.05).

Data Conclusion: DKI detected microstructural brain alterations in BD and MDD. Its indices may be useful to distinguish the two disorders or to reflect disease severity and duration.

Level Of Evidence: 2 TECHNICAL EFFICACY STAGE: 3 J. Magn. Reson. Imaging 2020;52:1187-1196.
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http://dx.doi.org/10.1002/jmri.27174DOI Listing
October 2020

Establishment of the novel bivalve body plan through modification of early developmental events in mollusks.

Evol Dev 2020 11 14;22(6):463-470. Epub 2020 Apr 14.

Pearl Research Institute, K. Mikimoto & Co., Ltd., Shima, Mie, Japan.

Mollusks have a wide variety of body plans, which develop through conserved early embryogenesis, namely spiral embryonic development and trochophore larvae. Although the comparative study of mollusks has attracted the interest of evolutionary developmental biology researchers, less attention has been paid to bivalves. In this review, we focused on the evolutionary process from single-shell ancestors to bivalves, which possess bilaterally separated shells. Our study tracing the lineage of shell field cells in bivalves did not support the old hypothesis that shell plate morphology is due to modification of the spiral cleavage pattern. Rather, we suggest that modification of the shell field induction process is the key to understanding the evolution of shell morphology. The novel body plan of bivalves cannot be established solely via separating shell plates, but rather requires the formation of additional organs, such as adductor muscles. The evolutionary biology of bivalves offers a unique view on how multiple organs evolve in a coordinated manner to establish a novel body plan.
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http://dx.doi.org/10.1111/ede.12334DOI Listing
November 2020

[A Case in Which Trastuzumab Combined Chemotherapy Was Effective for Recurrence of Post-Operative Gastric Cancer with Partial HER2 Overexpression].

Gan To Kagaku Ryoho 2019 Dec;46(13):2027-2029

Division of Gastroenterological Surgery, Clinical Oncology Center, Aomori Prefectural Central Hospital.

We report a case in which recurrent partial HER2-positive gastric cancer showed complete clinical response to capecitabine (Cape)/oxaliplatin(L-OHP/OX)(CapeOX)plus trastuzumab(Tmab)combined chemotherapy for 32months. A 65-yearold man underwent distal gastrectomy, D2 lymph node dissection, and Roux-en-Y reconstruction for type 2 gastric cancer of the prepyloric anterior wall in December 2014. Pathological stage was as follows: L, ant, Type 2, 32×22 mm, tub1>tub2> por1, pT2(MP), int>med, INF c>a, Ly1a, V0, pN0, cM0, cH0, cP0, pCY0, pStage I B, pPM0(60mm), pDM0(75mm), pR0. Immunostaining of the tumor indicated overexpression of the HER2 gene in more than 10% of the well differentiated tubular adenocarcinoma(tub1). Nineteen months post-surgery, pancreatic head lymph node metastasis was diagnosed, and we started CapeOX plus Tmab combined chemotherapy. After 19 courses, the metastatic lymph node reduced its size until we could not detect it on CT. We continued treatment for 45 courses(about 32 months). During the courses, there were adverse events such as peripheral neuropathy(Grade 3, CTCAE v5.0), which required interruption of L-OHP, and oral mucosal ulcer (Grade 2).
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December 2019

Influence of Childhood Maltreatment, Adulthood Stressful Life Events, and Affective Temperaments on Premenstrual Mental Symptoms of Nonclinical Adult Volunteers.

Neuropsychiatr Dis Treat 2020 6;16:1-10. Epub 2020 Jan 6.

Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.

Background: Previous studies have shown that childhood maltreatment is associated with premenstrual dysphoric disorder (PMDD). In this study we analyzed how multiple factors, such as childhood maltreatment, affective temperaments, and adult life events influence the severity of premenstrual mental (PMM) symptoms in nonclinical adult volunteers from the community.

Methods: A total of 204 participants were recruited and administered the following self-administered questionnaire surveys: PMDD scale, visual analogue scale, Patient Health Questionnaire-9, Life Experience Survey, Temperament Evaluation of Memphis, Pisa, Paris, and San Diego autoquestionnaire version, and the Child Abuse and Trauma scale. In addition to single and multiple regression analyses, structural equation modeling was used for the statistical analyses.

Results: A history of neglect indirectly predicted PMM symptoms through affective temperaments in nonclinical adult volunteers. Three affective temperaments (irritable, cyclothymic, and anxious) directly predicted PMM symptoms.

Conclusion: This study is the first to report that childhood maltreatment, particularly neglect, indirectly predicted PMM symptoms through affective temperaments. The results of our study suggest that affective temperament is a mediator of the influence of childhood maltreatment on PMM symptoms.
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http://dx.doi.org/10.2147/NDT.S232925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6954089PMC
January 2020

Influence of Childhood Maltreatment, Adulthood Stressful Life Events, and Affective Temperaments on Premenstrual Mental Symptoms of Nonclinical Adult Volunteers.

Neuropsychiatr Dis Treat 2020 6;16:1-10. Epub 2020 Jan 6.

Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.

Background: Previous studies have shown that childhood maltreatment is associated with premenstrual dysphoric disorder (PMDD). In this study we analyzed how multiple factors, such as childhood maltreatment, affective temperaments, and adult life events influence the severity of premenstrual mental (PMM) symptoms in nonclinical adult volunteers from the community.

Methods: A total of 204 participants were recruited and administered the following self-administered questionnaire surveys: PMDD scale, visual analogue scale, Patient Health Questionnaire-9, Life Experience Survey, Temperament Evaluation of Memphis, Pisa, Paris, and San Diego autoquestionnaire version, and the Child Abuse and Trauma scale. In addition to single and multiple regression analyses, structural equation modeling was used for the statistical analyses.

Results: A history of neglect indirectly predicted PMM symptoms through affective temperaments in nonclinical adult volunteers. Three affective temperaments (irritable, cyclothymic, and anxious) directly predicted PMM symptoms.

Conclusion: This study is the first to report that childhood maltreatment, particularly neglect, indirectly predicted PMM symptoms through affective temperaments. The results of our study suggest that affective temperament is a mediator of the influence of childhood maltreatment on PMM symptoms.
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http://dx.doi.org/10.2147/NDT.S232925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6954089PMC
January 2020

Pilot Validation Study of the Japanese Translation of the Brief Negative Symptoms Scale (BNSS).

Neuropsychiatr Dis Treat 2019 23;15:3511-3518. Epub 2019 Dec 23.

Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.

Purpose: The brief negative symptoms scale (BNSS) is a concise instrument used to assess negative symptoms of subjects with schizophrenia covering five domains of negative symptoms and is suitable for use in clinical, experimental, and epidemiological settings. The original and translated version of BNSS has thus far been shown to have adequate psychometric properties. This study aimed to examine internal consistency, inter-rater and test-retest reliability, discriminant and convergent validity, and factor structure of the Japanese version of BNSS.

Patients And Methods: The assessment was performed by 11 raters using interview videos of nine subjects. Reliability was calculated with Cronbach's alpha for internal consistency and intra class correlation coefficient (ICC) for inter-rater reliability. Pearson's correlation coefficients were calculated to estimate the test-retest reliability. In addition to BNSS, Scale for assessment of negative symptoms (SANS) and scale for assessment of positive symptoms (SAPS) was obtained to assess the convergent and discriminant validity. Factor structure was assessed using principle factor analysis.

Results: The Japanese BNSS showed excellent internal consistency (Cronbach's alpha=0.95), inter-rater reliability (intra class correlation coefficient=0.97), and test-retest reliability (r=0.94, p<0.001). The convergent validity shown by correlation with SANS total score (r=0.87, p<0.001) and discriminant validity shown by correlation with SAPS total score (r=0.17, p=-0.68) were also good. Principal factor analysis revealed a two-factor structure of BNSS, although the loading of each item differed from that in the literature.

Conclusion: Our pilot study demonstrated that Japanese BNSS had good psychometric properties which were achieved with relatively brief training. Further studies with more subjects and raters with various backgrounds recruited from multiple sites are warranted.
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http://dx.doi.org/10.2147/NDT.S237449DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6934108PMC
December 2019

White matter microstructural alterations across four major psychiatric disorders: mega-analysis study in 2937 individuals.

Mol Psychiatry 2020 04 29;25(4):883-895. Epub 2019 Nov 29.

Department of Psychiatry, Tokushima University Hospital, Tokushima, Japan.

Identifying both the commonalities and differences in brain structures among psychiatric disorders is important for understanding the pathophysiology. Recently, the ENIGMA-Schizophrenia DTI Working Group performed a large-scale meta-analysis and reported widespread white matter microstructural alterations in schizophrenia; however, no similar cross-disorder study has been carried out to date. Here, we conducted mega-analyses comparing white matter microstructural differences between healthy comparison subjects (HCS; N = 1506) and patients with schizophrenia (N = 696), bipolar disorder (N = 211), autism spectrum disorder (N = 126), or major depressive disorder (N = 398; total N = 2937 from 12 sites). In comparison with HCS, we found that schizophrenia, bipolar disorder, and autism spectrum disorder share similar white matter microstructural differences in the body of the corpus callosum; schizophrenia and bipolar disorder featured comparable changes in the limbic system, such as the fornix and cingulum. By comparison, alterations in tracts connecting neocortical areas, such as the uncinate fasciculus, were observed only in schizophrenia. No significant difference was found in major depressive disorder. In a direct comparison between schizophrenia and bipolar disorder, there were no significant differences. Significant differences between schizophrenia/bipolar disorder and major depressive disorder were found in the limbic system, which were similar to the differences in schizophrenia and bipolar disorder relative to HCS. While schizophrenia and bipolar disorder may have similar pathological characteristics, the biological characteristics of major depressive disorder may be close to those of HCS. Our findings provide insights into nosology and encourage further investigations of shared and unique pathophysiology of psychiatric disorders.
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http://dx.doi.org/10.1038/s41380-019-0553-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7156346PMC
April 2020

Improvement of psychiatrists' clinical knowledge of the treatment guidelines for schizophrenia and major depressive disorders using the 'Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment (EGUIDE)' project: A nationwide dissemination, education, and evaluation study.

Psychiatry Clin Neurosci 2019 Oct 22;73(10):642-648. Epub 2019 Aug 22.

Department of Neuropsychiatry, Kanazawa Medical University, Ishikawa, Japan.

Aim: Although treatment guidelines for pharmacological therapy for schizophrenia and major depressive disorder have been issued by the Japanese Societies of Neuropsychopharmacology and Mood Disorders, these guidelines have not been well applied by psychiatrists throughout the nation. To address this issue, we developed the 'Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment (EGUIDE)' integrated education programs for psychiatrists to disseminate the clinical guidelines. Additionally, we conducted a systematic efficacy evaluation of the programs.

Methods: Four hundred thirteen out of 461 psychiatrists attended two 1-day educational programs based on the treatment guidelines for schizophrenia and major depressive disorder from October 2016 to March 2018. We measured the participants' clinical knowledge of the treatment guidelines using self-completed questionnaires administered before and after the program to assess the effectiveness of the programs for improving knowledge. We also examined the relation between the participants' demographics and their clinical knowledge scores.

Results: The clinical knowledge scores for both guidelines were significantly improved after the program. There was no correlation between clinical knowledge and participant demographics for the program on schizophrenia; however, a weak positive correlation was found between clinical knowledge and the years of professional experience for the program on major depressive disorder.

Conclusion: Our results provide evidence that educational programs on the clinical practices recommended in guidelines for schizophrenia and major depressive disorder might effectively improve participants' clinical knowledge of the guidelines. These data are encouraging to facilitate the standardization of clinical practices for psychiatric disorders.
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http://dx.doi.org/10.1111/pcn.12911DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6852015PMC
October 2019

Switching to antipsychotic monotherapy vs. staying on antipsychotic polypharmacy in schizophrenia: A systematic review and meta-analysis.

Schizophr Res 2019 07 8;209:50-57. Epub 2019 Jun 8.

Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan. Electronic address:

Background: While recent meta-analyses have reported the superiority of antipsychotic polypharmacy (APP) over antipsychotic monotherapy (APM) in schizophrenia, switching to APM can be beneficial in terms of side effects. To determine whether patients receiving APP should switch to APM or stay on APP, we conducted a systematic review and meta-analysis.

Methods: Randomized controlled trials (RCTs) examining a switch from APP to APM vs. staying on APP were systematically selected from a previous meta-analysis comparing APP with APM in patients with schizophrenia. In addition, we conducted an updated systematic literature search using MEDLINE, Embase, and Cochrane Central Register of Controlled Trials. Data on study discontinuation, relapse, psychopathology, neurocognition, extrapyramidal symptoms, and body weight/body mass index (BMI) were extracted and synthesized.

Results: A total of 6 RCTs involving 341 patients were included. All studies examined a switch from 2 antipsychotic agents to a single agent. Clozapine-treated patients were included in 3 studies. There was a significant difference in study discontinuation due to all causes in favor of staying on APP (N = 6, n = 341, RR = 2.28, 95% CI = 1.50-3.46, P < 0.001). There were no significant differences in relapse, any psychopathology, neurocognition, extrapyramidal symptoms, or body weight/BMI between the 2 groups. The quality of evidence was low to very low.

Conclusions: The findings suggest that clinicians should closely monitor patient condition when switching to APM after receiving 2 antipsychotics. Given the low to very low overall quality of the evidence, the findings should be considered preliminary and inconclusive.
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http://dx.doi.org/10.1016/j.schres.2019.05.030DOI Listing
July 2019

Investigating the role of genetic counseling in neuromuscular disease considering life events.

J Hum Genet 2019 Jun 13;64(6):551-559. Epub 2019 Mar 13.

Division of Clinical Genetics, Hokkaido University Hospital, Sapporo, Japan.

Genetic diagnoses are becoming a routine in the medical practice of neuromuscular diseases. Many diagnoses, however, can have an influence on relatives and family members and thus must be handled carefully by genetic counseling (GC). Here, we aimed to assess the purpose of undergoing GC to verify the utility of collaborations between clinical and genetic divisions. We investigated consecutive GC cases of neuromuscular disease and examined the role of GC. Our study included 102 cases who underwent GC in our hospital from July 2005 to March 2018: 86.3% were women and 45.1% were in their 30's. Disease explanation was the most common reason for attending GC (29.4%), followed by prenatal diagnosis (25.5%), pre-symptomatic diagnosis (17.6%), and carrier diagnosis (14.7%). Clients typically visited the hospital for GC when some kind of life event occurred, such as marriage, had a desire to bear a child, or a change in the condition of the proband. Clinicians should be conscious of such life events from the perspective of both the client and their relatives, and guide the GC at an appropriate time. Overall, the degree of recognition of genetic risk by clients differed; thus, it is important for GC to determine the status of each unique situation and respond individually.
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http://dx.doi.org/10.1038/s10038-019-0590-8DOI Listing
June 2019
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