Publications by authors named "Masaomi Iyo"

328 Publications

Characteristics of Early-Onset Dementia in Chiba Prefecture, Japan: A Multicenter Survey.

Dement Geriatr Cogn Disord 2021 Aug 26:1-6. Epub 2021 Aug 26.

Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, Japan.

Introduction: Early-onset dementia (EOD), defined as dementia onset before the age of 65 years, is relatively rare, but its social impacts are significant. This study aimed to characterize the diagnosis and clinical and social status of EOD subjects in the 11 dementia centers in Chiba Prefecture, Japan.

Methods: A retrospective 1-year survey was conducted. Collected data included clinical diagnosis, age at onset, age at survey, neuropsychological test, family history, employment, and living status.

Results: We identified 208 EOD subjects, including 123 (59.4%), 24 (11.6%), 21 (10.1%), 17 (8.2%), and 10 (4.8%) with Alzheimer's disease (AD), vascular dementia, frontotemporal lobar degeneration (FTLD), dementia with Lewy bodies/Parkinson's disease dementia, and alcohol-related dementia, respectively. The Mini-Mental State Examination (MMSE) score <24 was observed in 50-75% of patients and was not correlated with disease duration. Twenty-four (16.4%) subjects had positive family history of EOD. EOD subjects were at risk of early retirement, and 133 subjects lived with their family, in whom 64 (30.8%) lived with their child.

Conclusion: In dementia centers, AD, FTLD, and Lewy body dementia had relatively large proportion. Employment, economy, and social supports are urgently needed for EOD subjects and their family.
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http://dx.doi.org/10.1159/000518294DOI Listing
August 2021

Safety and Effectiveness of Lurasidone in Patients with Schizophrenia: A 12-Week, Open-Label Extension Study.

Neuropsychiatr Dis Treat 2021 16;17:2683-2695. Epub 2021 Aug 16.

Japan Depression Center, Tokyo, Japan.

Purpose: The goal of this study was to evaluate the safety and effectiveness of lurasidone among patients with schizophrenia in a 12-week open-label extension study.

Patients And Methods: Patients who completed a 6-week, double-blind, placebo-controlled study were enrolled in a 12-week open-label extension study with flexible dosing of lurasidone at 40 or 80 mg/day. Safety assessments included adverse events, vital signs, laboratory tests, and electrocardiogram (ECG) parameters. Effectiveness measures included the Positive and Negative Syndrome Scale (PANSS) total score, Clinical Global Impression-Severity Scale (CGI-S), Calgary Depression Scale for Schizophrenia (CDSS) and quality of life measure.

Results: A total of 289 patients were enrolled in the open-label extension study. Rates of treatment-emergent adverse events (TEAEs) were low; akathisia was the most common TEAE with an incidence of 6.6%. There were 54 patients (18.7%) who discontinued the extension study, with 17 (5.9%) discontinuing due to adverse events. Minimal or no effects of lurasidone on weight, body mass index, metabolic parameters, prolactin, and ECG parameters were evident. There was continued improvement to week 12 in PANSS and CGI-S scores beyond the initial gains made during the prior 6-week double-blind study. Non-responders to lurasidone 40 mg/day in the prior 6-week study showed a mean (standard deviation) improvement from open-label baseline of 10.7 (13.8) points on the PANSS total score after lurasidone dose was increased to a modal dose of 80 mg/day during the extension study. Changes from double-blind baseline in CDSS and quality of life were maintained in the extension study.

Conclusion: Treatment with lurasidone 40 or 80 mg once daily (flexibly dosed) continued to be well tolerated with patients demonstrating further improvement in symptoms over the course of a 12-week open-label extension study in patients with schizophrenia.
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http://dx.doi.org/10.2147/NDT.S320021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8379682PMC
August 2021

Cyclothymic Temperament is Associated with Poor Medication Adherence and Disordered Eating in Type 2 Diabetes Patients: A Case-Control Study.

Diabetes Ther 2021 Sep 31;12(9):2611-2624. Epub 2021 Jul 31.

Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Kimitsu Chuo Hospital, Sakurai 1010, Kisarazu, Chiba, 292-0822, Japan.

Introduction: Poor medication adherence and disordered eating are major self-care problems in patients with type 2 diabetes that worsen glycemic control and increase the risk of developing severe diabetes complications. Affective temperament, which remains mostly unchanged throughout life, is speculated to predict poor treatment response and high comorbidity. The aim of this study was to explore the link between affective temperament and poor glycemic control due to insufficient self-care.

Methods: This single-center case-control study involved 77 outpatients divided into the 'poor glycemic control' group (n = 52) and the 'better glycemic control' group (n = 25) based on their mean glycated hemoglobin (HbA1c) levels over the past 12 months. All participants underwent one-on-one interviews during which they completed the following psychometric questionnaires: (1) the Mini-International Neuropsychiatric Interview 5.0.0; (2) the Temperament Evaluation of Memphis, Pisa, and San Diego Auto-questionnaire; (3) a researcher-designed single question for assessing subclinical stress-induced overeating; and (4) the Morisky Medication Adherence Scale. The difference between two continuous independent variables was determined using Student's t test. Discrete variables were compared using the Chi-square (χ) or Fisher's exact test. Multiple testing corrections were performed using the false discovery rate.

Results: Those outpatients in the poor glycemic control group exhibited significantly more stress-induced overeating (χ = 1.14, q statistic = 0.040) and poor medication adherence (t = 3.70, q = 0.034) than those in the better glycemic control group. However, there were no significant differences between the two groups in terms of affective temperaments, clinical eating disorders, or diabetes-specific distress. Patients with stress-induced overeating (t = - 2.99, p = 0.004) and poor medication adherence (t = - 4.34, p = 0.000) exhibited significantly higher scores for cyclothymic temperament than their counterparts.

Conclusion: Cyclothymic temperament is significantly associated with disordered eating and/or poor medication adherence in patients with type 2 diabetes and is possibly linked to poor glycemic control.
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http://dx.doi.org/10.1007/s13300-021-01121-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8384994PMC
September 2021

Risk factors for early-phase clozapine discontinuation: A nested case-control study.

Asian J Psychiatr 2021 Aug 26;62:102745. Epub 2021 Jun 26.

Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan. Electronic address:

Objectives: Safe and efficient methods for introducing clozapine to patients with treatment-resistant schizophrenia (TRS) are needed. We investigated risk factors for clozapine discontinuation in the early phase of its introduction.

Methods: We conducted a nested case-control study at 14 psychiatric hospitals in Chiba, Japan. Data from pre-registered TRS patients were collected at 7 time points within 12 weeks before and after the start of clozapine introduction. We examined the demographic data, prior and concomitant psychotropic drugs, strategies for switching from prior antipsychotics, and blood test and Global Assessment of Function results. The Clinical Global Impression-Severity Scale was retrospectively scored at 12 weeks before and after clozapine introduction.

Results: Of 228 patients, clozapine treatment was continued in 213 (93.4 %) and discontinued in 15 (6.6 %) patients within 12 weeks. Clinical symptoms were improved to mild symptoms with a response rate of 14.9 %. Prior antipsychotics and concomitant psychotropic drugs except for mood stabilizers were significantly decreased. Histories of smoking (OR = 3.32, 95 %CI: 1.11-9.93) and antipsychotic treatment at chlorpromazine-equivalent doses <1200 mg within the past 5 years (OR = 3.93, 95 %CI: 1.24-12.50), but not antipsychotic switching strategy, were associated with clozapine discontinuation. Eosinophilia was the most frequent reason for discontinuation (n = 3, 20 %) and was associated with concomitant valproate at 4 weeks after the introduction.

Conclusion: Clozapine is an effective option for TRS patients (especially those treated with higher doses of prior antipsychotics) in Japan. Clinicians should be cautious about concomitant valproate in the early phase of clozapine introduction due to a high risk of eosinophilia.
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http://dx.doi.org/10.1016/j.ajp.2021.102745DOI Listing
August 2021

Interacting Roles of COMT and GAD1 Genes in Patients with Treatment-Resistant Schizophrenia: a Genetic Association Study of Schizophrenia Patients and Healthy Controls.

J Mol Neurosci 2021 Jun 14. Epub 2021 Jun 14.

Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan.

The projection from dopaminergic neurons to gamma-aminobutyric acid (GABA) interneurons in the prefrontal cortex is involved in the etiology of schizophrenia. The impact of interacting effects between dopamine signals and the expression of GABA on the clinical phenotypes of schizophrenia has not been studied. Since these interactions could be closely involved in prefrontal cortex functions, patients with specific alleles of these relevant molecules (which lead to lower or vulnerable genetic functions) may develop treatment-refractory symptoms. We conducted a genetic association study focusing on COMT and GAD1 genes for a treatment-resistant schizophrenia (TRS) group (n=171), a non-TRS group (n=592), and healthy controls (HC: n=447), and we examined allelic combinations specific to TRS. The results revealed that the percentage of subjects with Met allele of rs4680 on the COMT gene and C/C homozygote of rs3470934 on the GAD1 gene was significantly higher in the TRS group than the other two groups. There was no significant difference between the non-TRS group and HC groups. Considering the direction of functions of these single-nucleotide polymorphisms revealed by previous studies, we speculate that subjects with the Met/CC allelic combination could have a higher dopamine level and a lower expression of GABA in the prefrontal cortex. Our results suggest that an interaction between the dopaminergic signal and GABA signal intensities could differ between TRS patients and patients with other types of schizophrenia and healthy subjects.
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http://dx.doi.org/10.1007/s12031-021-01866-yDOI Listing
June 2021

Clozapine Prolongs Cortical Silent Period in Patients with Treatment-Resistant Schizophrenia.

Psychopharmacol Bull 2021 Mar;51(2):20-30

Miyazawa, MD, Nakata, MD, PhD, Atsushi Kimura, MD, PhD, Oda, MD, PhD, Iyo, MD, PhD, Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan. Kanahara, MD, PhD, Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan, Division of Medical Treatment and Rehabilitation, Center for Forensic Mental Health, Chiba University, Chiba, Japan. Kodama, MD, PhD, Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. Hiroshi Kimura, MD, PhD, Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan, Department of Psychiatry, Gakuji-kai Kimura Hospital, Chiba, Japan, Department of Psychiatry, International University of Health and Welfare, Chiba, Japan. Watanabe, MD, PhD, Division of Medical Treatment and Rehabilitation, Center for Forensic Mental Health, Chiba University, Chiba, Japan, Department of Psychiatry, Gakuji-kai Kimura Hospital, Chiba, Japan.

Objectives: Although clozapine exhibited high efficacy for treating the symptoms of patients with treatment-resistant schizophrenia (TRS), its precise action mechanisms have not been fully understood. Recently, accumulating evidence has suggested the presence of abnormalities in the gamma-aminobutyric acid (GABA) systems in patients with schizophrenia, and the potential effects of clozapine on GABA receptors have gained a great deal of attention.

Experimental Designs: In the present study, the cortical silent period (CSP), an electrophysiological parameter of GABA function via GABA receptors, was measured using with the transcranial magnetic stimulation in patients with schizophrenia and healthy control subjects. Then the CSP of patients treated with clozapine (N = 12) was compared with that of patients treated with other antipsychotics (N = 25) and with that of healthy controls (N = 27).

Principal Observations: The CSP of the patients treated with clozapine was significantly longer compared to those of the other two groups. The CSP of patients treated with other antipsychotics was similar to that of healthy subjects. There was a positive correlation between CSP and global assessment of function (GAF) in patients with TRS.

Conclusions: The present study indicated that CSP was prolonged in patients receiving clozapine, and suggested that clozapine enhances the transmission signal via GABAB receptors.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146563PMC
March 2021

Serum levels of glial cell line-derived neurotrophic factor as a biomarker for mood disorders and lithium response.

Psychiatry Res 2021 Jul 27;301:113967. Epub 2021 Apr 27.

Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan; Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan.

Glial cell line-derived neurotrophic factor (GDNF) plays an important role in the pathophysiology of neuropsychiatric disorders. We examined serum GDNF levels in bipolar disorder (BD) patients and major depressive disorder (MDD) patients and their association with response to lithium therapy. We used a multicenter (six sites), exploratory, cross-sectional case-control design and recruited 448 subjects: 143 BD patients, 116 MDD patients, and 158 healthy controls (HCs). We evaluated the patients' clinical severity using the Clinical Global Impression (CGI), and responses to lithium therapy using the Alda scale. The serum GDNF levels were significantly decreased in the BD and MDD groups compared to the HCs, with no significant difference between the BD and MDD groups. After adjustment, the serum GDNF levels in the BD and MDD patients in remission or depressive states were decreased compared to the HC values. Lower serum GDNF levels in BD patients were associated with higher CGI and Alda scores (i.e., severe illness and good response to lithium therapy, respectively). Our findings suggest that the serum GDNF level may be a biomarker for both BD and MDD in remission or depressive states. The serum GDNF level may be associated with the lithium response of BD patients.
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http://dx.doi.org/10.1016/j.psychres.2021.113967DOI Listing
July 2021

Identifying factors associated with criminal responsibility by analyzing court trial verdicts.

Int J Law Psychiatry 2021 Jul-Aug;77:101702. Epub 2021 May 4.

Chiba University Center for Forensic Mental Health, Inohana 1-8-1, Chuo-ku, Chiba-shi, Chiba, Japan. Electronic address:

The criminal responsibility of offenders with mental disorders is a key issue in forensic psychiatry. Japan's implementation of the Medical Treatment and Supervision Act and Lay Judge Act in the early 2000s raised public awareness of this issue. To determine how criminal court judges in Japan assess the criminal responsibility of offenders, we examined 453 district court verdicts that mention psychiatric evidence. We extracted elements from each verdict that may be associated with courts' decision-making regarding criminal responsibility and analyzed the relationship between each element and the adjudication of criminal responsibility. We investigated the changes in each element's prevalence over time. A logistic regression analysis revealed that the following were independently associated with the court decisions that offenders' criminal responsibility was intact: understandable motivation for committing the offense, homogeneity of the offense from the defendant's usual behavioral pattern, a coherent process used to commit the offense, alertness while offending, and absence of psychotic symptoms. We observed that recent verdicts are more focused on the offender's perception of illegality and the coherence of the offending process while disregarding the defendant's consciousness and memory while offending. Thus, the courts focus on some specific elements for evaluating the criminal responsibility of each offender.
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http://dx.doi.org/10.1016/j.ijlp.2021.101702DOI Listing
May 2021

Efficacy and safety of lurasidone in acutely psychotic patients with schizophrenia: A 6-week, randomized, double-blind, placebo-controlled study.

Psychiatry Clin Neurosci 2021 Apr 23. Epub 2021 Apr 23.

Japan Depression Center, Tokyo, Japan.

Aim: The aim of this study was to evaluate the efficacy of lurasidone in acute schizophrenia in Japan and other countries.

Methods: Subjects (aged 18-74 years) diagnosed with schizophrenia were randomized to lurasidone 40 mg/day or placebo. The primary efficacy endpoint was change from baseline on the Positive and Negative Syndrome Scale (PANSS) total score at Week 6. Secondary efficacy assessments included the Clinical Global Impression-Severity Scale (CGI-S). Safety endpoints included adverse events, and laboratory and electrocardiogram parameters.

Results: A total of 483 subjects were randomized to lurasidone or placebo; 107 subjects were from Japan. Mean changes from baseline at Week 6 endpoint in PANSS total scores were -19.3 in the lurasidone group and -12.7 in the placebo group (treatment difference: P < 0.001, effect size = 0.41). Changes from baseline for Week 6 CGI-S scores were -1.0 for lurasidone and -0.7 for placebo (treatment difference: P < 0.001, effect size = 0.41). All-cause discontinuation during the 6-week, double-blind period was 19.4% for lurasidone and 25.4% for placebo, and discontinuation rates due to adverse event were 5.7% for lurasidone and 6.4% for placebo. The following common treatment-emergent adverse events occurred in more than 2% on lurasidone and at a rate at least twice that of the placebo group: akathisia (4.0%), dizziness (2.8%), somnolence (2.8%), abdominal discomfort (2.0%) and asthenia (2.0%). No significant changes in bodyweight or metabolic parameters were observed.

Conclusion: Lurasidone 40 mg once daily dosing demonstrated efficacy in a patient population with acute schizophrenia, including subjects from Japan, and was generally safe and well-tolerated.
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http://dx.doi.org/10.1111/pcn.13221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8361730PMC
April 2021

Possible effect of blonanserin on gambling disorder: A clinical study protocol and a case report.

World J Clin Cases 2021 Apr;9(11):2469-2477

Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan.

Background: Gambling disorder is characterized by excessive and recurrent gambling and can have serious negative social consequences. Although several psychotherapeutic and pharmacological approaches have been used to treat gambling disorder, new treatment strategies are needed. Growing evidence suggests that dopamine D3 receptor plays a specific role in the brain reward system.

Aim: To investigate if blonanserin, a dopamine D3 receptor antagonist, would be effective in reducing gambling impulses in patients with gambling disorder.

Methods: We developed a study protocol to measure the efficacy and safety of blonanserin as a potential drug for gambling disorder, in which up to 12 mg/d of blonanserin was prescribed for 8 wk.

Results: A 37-year-old female patient with gambling disorder, intellectual disability, and other physical diseases participated in the pilot study. The case showed improvement of gambling symptoms without any psychotherapy. However, blonanserin was discontinued owing to excessive saliva production.

Conclusion: This case suggests that blonanserin is potentially an effective treatment for patients with gambling disorder who resist standard therapies, but it also carries a risk of adverse effects. Further studies are needed to confirm the findings.
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http://dx.doi.org/10.12998/wjcc.v9.i11.2469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040182PMC
April 2021

Oxytocin system dysfunction in patients with treatment-resistant schizophrenia: Alterations of blood oxytocin levels and effect of a genetic variant of OXTR.

J Psychiatr Res 2021 06 30;138:219-227. Epub 2021 Mar 30.

Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan.

Treatment-resistant schizophrenia (TRS) has a quite complex pathophysiology that includes not only severe positive symptoms but also other symptom domains. Much attention has been devoted to the overlapping psychological and biological profiles of schizophrenia and autistic spectrum disorder (ASD). We compared TRS patients (n = 30) with schizophrenia patients in remission (RemSZ, n = 28) and ASD patients (n = 28), focusing on general cognitive and social cognitive impairment and oxytocin system dysfunction. Our analyses revealed that there was no difference in oxytocin concentration among the three groups. The TRS patients' oxytocin blood concentrations were positively correlated with their processing speed and theory-of-mind scores, whereas the RemSZ and ASD groups had no significant relation with any measures. Rs53576, a single nucleotide polymorphism on the oxytocin receptor gene, affected social cognition abilities in the schizophrenia group. Although the overall findings are preliminary, they indicate that oxytocin system dysfunction could be involved in the serious cognitive deficits in TRS patients. Further, these results suggest that patients with TRS might have early neurodevelopmental abnormalities based on their shared biological features with ASD patients.
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http://dx.doi.org/10.1016/j.jpsychires.2021.03.053DOI Listing
June 2021

Establishment of a Japanese version of the Sick, Control, One Stone, Fat, and Food (SCOFF) questionnaire for screening eating disorders in university students.

BMC Res Notes 2021 Apr 16;14(1):142. Epub 2021 Apr 16.

Department of Psychiatry, School of Medicine, International University of Health and Welfare, 4-3, Kozunomori, Chiba, 286-8686, Japan.

Objective: This study aimed to validate the Sick, Control, One stone, Fat, and Food (SCOFF) questionnaire in relation to the Eating Disorders Examination Questionnaire (EDE-Q) and to examine the appropriateness of a question concerning weight loss among Japanese university students. The psychometric properties of the two Japanese versions were determined among 649 Japanese college students. The original version (SCOFF-O) employed the original item 3, whereas the revised version (SCOFF-2.5) modified the item to "Have you recently lost more than 2.5 kg within three months?" Validity was tested relative to EDE-Q.

Results: The test-retest reliabilities of SCOFF-O and SCOFF-2.5 were 0.52 and 0.57, while the correlations of SCOFF-O and SCOFF-2.5 with EDE-Q were r = 0.53 and r = 0.56. The sensitivity and specificity of SCOFF-O were 65.2 and 89.7, and those of SCOFF-2.5 were 69.5 and 86.5, respectively. There were significant correlations between the question concerning losing 2.5 kg and the EDE-Q subscales. The Japanese version of SCOFF-2.5 is an appropriate tool for the early screening of eating disorders among Japanese university students.
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http://dx.doi.org/10.1186/s13104-021-05549-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8052679PMC
April 2021

Identification of psychological features and development of an assessment tool for event-related psychological distress after experiencing non-traumatic stressful events.

PLoS One 2021 31;16(3):e0249126. Epub 2021 Mar 31.

Department of Psychiatry, Graduate School of Medicine, Chiba University, Chiba, Japan.

Stressful events in daily life that are non-traumatic (e.g., family-, school-, work-, interpersonal-, and health-related problems) frequently cause various mood disturbances. For some people, being exposed to non-traumatic but stressful events could trigger the onset and relapse of mood disorders. Furthermore, non-traumatic stressful events also cause event-related psychological distress (ERPD), similar to that of post-traumatic stress disorder (PTSD; i.e., intense intrusive imagery or memory recall, avoidance, and hyperarousal) in the general population and individuals with mood disorders. However, previous ERPD studies only showed that people with ERPD display PTSD-like symptoms after non-traumatic experiences; they failed to get to the crux of the matter by only utilizing trauma- or PTSD-related assessment tools. We thus aimed to identify the psychological phenomena and features of ERPD after individuals experienced non-traumatic stressful events, and to develop and validate an appropriate ERPD assessment tool. First, we conducted a qualitative study to obtain the psychological features through interviews with 22 individuals (mean age = 41.50 years old, SD = 12.24) with major depressive disorder or bipolar disorder. Second, in the quantitative component, we implemented a web-based survey with 747 participants of the general population (mean age = 41.96 years old, SD = 12.64) by using ERPD-related questionnaires created based on the qualitative study; then, we examined the reliability and validity of the ERPD assessment tool. Results yielded that the psychological features of ERPD comprised four factors: feelings of revenge, rumination, self-denial, and mental paralysis. These were utilized in the developed 24-item measure of ERPD-a novel self-report assessment tool. For various professionals involved in mental healthcare, this tool can be used to clarify and assess psychological phenomena in people with ERPD.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0249126PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011732PMC
March 2021

Perception of and anxiety about COVID-19 infection and risk behaviors for spreading infection: an international comparison.

Ann Gen Psychiatry 2021 Feb 18;20(1):13. Epub 2021 Feb 18.

Center for Forensic Mental Health, Chiba University, 260-8670 Inohana 1-8-1, Chuo-ku, Chiba, Japan.

Background: To control the spread of the new SARS-CoV-2 infection's disease (COVID-19), appropriate precautionary behaviors by the public should be promoted. There are international differences in public cognitive and behavioral pattern, attitudes toward information sources, and anxiety about COVID-19. Information about these differences could increase understanding of the patterns of epidemic-related anxiety and behavior, and would help optimize future policies for preventing the next wave of the epidemic.

Methods: To examine between-country differences in perception, attitude, and precautionary behaviors toward COVID-19, we conducted a cross-sectional study using an online questionnaire survey. Participants were adults who had been registered in Cross Marketing Group Inc. and living in the UK, Spain, or Japan. A total of 8,000 people stratified by age were recruited on a first-come, first-serve basis. Knowledge of and anxiety about COVID-19, the frequency of access and perceived credibility of several information sources, and the frequency of each precautionary behavior were examined on March 27-28, 2020, in Japan and April 17-21, 2020, in the UK and Spain.

Results: Knowledge, anxiety, and the frequency of precautionary behaviors were higher in the UK and Spain than in Japan. Participants with infected acquaintances were more concerned about COVID-19. However, participants in the UK rarely wore a medical mask. Participants in the UK and Spain were more eager to obtain information about COVID-19 than those in Japan. Participants in Spain tended not to trust official information and to believe specialists' comments instead.

Conclusion: The rapidity of the spread of COVID-19, cultural background, and recent political situations seemed to contribute to the international differences here.
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http://dx.doi.org/10.1186/s12991-021-00334-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890773PMC
February 2021

Recent discussions on dopamine supersensitivity psychosis: Eight points to consider when diagnosing treatment-resistant schizophrenia.

Curr Neuropharmacol 2021 Jan 25. Epub 2021 Jan 25.

Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba. Japan.

Dopamine supersensitivity psychosis is a clinical concept characterized by an unstable psychotic state and tardive dyskinesia in schizophrenia patients at the chronic stage. This state is thought to be induced by a compensatory upregulation of dopamine D2 receptors, which is provoked by long-term and/or high-dose medications. Recent clinical data suggest that patients who responded well to medication but later exhibit dopamine supersensitivity develop tolerance to antipsychotics' effects and eventually transit to treatment-resistant schizophrenia, indicating that dopamine supersensitivity could be an etiology contributing to treatment-resistant schizophrenia. However, any clinicians and researchers consider dopamine supersensitivity psychosis a minor phenomenon during the clinical course and do not make much of it. This opinion is often based on numerous clinical data which indicating that dopamine supersensitivity psychosis is a relatively rare event. This review examines the data dealing with dopamine supersensitivity with the five themes of frequency, severity, withdrawal studies, switching to aripiprazole, and tardive dyskinesia. These themes' effects on discussions of the clinical meaning of dopamine supersensitivity psychosis are then reviewed. The present review will help clinicians to speculate as to the background of severe psychopathology in a given patient; to make diagnoses of treatment-resistant schizophrenia and dopamine supersensitivity psychosis; and to plan antipsychotic medication regimens with the goal of achieving better long-term prognosis.
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http://dx.doi.org/10.2174/1570159X19666210125152815DOI Listing
January 2021

Need for self-medication using over-the-counter psychoactive agents: A national survey in Japan.

PLoS One 2021 25;16(1):e0245866. Epub 2021 Jan 25.

Department of Psychiatry, Graduate School of Medicine, Chiba University, Chiba, Japan.

Self-medication using over-the-counter (OTC) drugs is an option for the autonomous treatment of several health problems. However, the use of OTC drugs to treat psychiatric conditions remains controversial. To clarify opinions regarding the use of OTC drugs to treat psychiatric problems, we conducted an anonymous online survey of 3000 people in Japan. Participants were stratified into three groups according to their history of mental health problems. Few participants had engaged in self-medication using OTC drugs for psychiatric symptoms, with the exception of insomnia. Participants who had used OTC drugs reported feeling less satisfied with their experience compared with those who had consulted a specialist. Participants who had used sleeping pills were likely to hold relatively positive opinions regarding the use of OTC psychiatric drugs. In conclusion, the need for self-medication of psychiatric symptoms appears to be limited. Education and further research may be necessary to promote self-medication for proper treatment of psychiatric conditions in Japan.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245866PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833153PMC
June 2021

Reduction of dopamine and glycogen synthase kinase-3 signaling in rat striatum after continuous administration of haloperidol.

Pharmacol Biochem Behav 2021 03 22;202:173114. Epub 2021 Jan 22.

Department of Psychiatry, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuou-ku, Chiba, Chiba 260-8670, Japan.

Background: Some individuals with schizophrenia present with a dopamine supersensitivity state (DSS) induced by a long-term administration of excessive antipsychotics; this is recognized as dopamine supersensitivity psychosis (DSP). The mechanisms underlying DSP are not established. Here, we investigated dopamine signaling in DSS rats.

Methods: Haloperidol (HAL; 0.75 mg/kg/day for 14 days) or vehicle was administered to rats via an osmotic mini-pump. We then screened DSS rats from HAL-treated rats by a voluntary locomotion test. The striatal levels of dopamine (DA) and its metabolites 3,4-hydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were determined, as were the levels of protein kinase v-akt murine thymoma viral oncogene homolog (AKT), glycogen synthase kinase-3 (GSK-3), and phosphorylated GSK-3 in the striatal regions.

Results: In the DSS rats, the DA, DOPAC, and HVA levels were significantly decreased. In a western blot analysis, the DSS rats exhibited a significant decrease in GSK-3α/β and an increase in the pGSK-3β/GSK-3β ratio, whereas AKT was not changed.

Conclusions: Our results indicated that the DSS rats had hypofunction of the basal dopamine release and AKT/GSK-3 signaling even at 7 days after the antipsychotic was discontinued. Protracted reductions in pre- and post-dopamine D2 receptor signaling might cause prolonged DSS.
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http://dx.doi.org/10.1016/j.pbb.2021.173114DOI Listing
March 2021

Rationale and neurobiological effects of treatment with antipsychotics in patients with chronic schizophrenia considering dopamine supersensitivity.

Behav Brain Res 2021 04 15;403:113126. Epub 2021 Jan 15.

Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan.

The long-term treatment of patients with schizophrenia often involves the management of relapses for most patients and the development of treatment resistance in some patients. To stabilize the clinical course and allow as many patients as possible to recover, clinicians need to recognize dopamine supersensitivity, which can be provoked by administration of high dosages of antipsychotics, and deal with it properly. However, no treatment guidelines have addressed this issue. The present review summarized the characteristics of long-acting injectable antipsychotics, dopamine partial agonists, and clozapine in relation to dopamine supersensitivity from the viewpoints of receptor profiles and pharmacokinetics. The potential merits and limitations of these medicines are discussed, as well as the risks of treating patients with established dopamine supersensitivity with these classes of drugs. Finally, the review discussed the biological influence of antipsychotic treatment on the human brain based on findings regarding the relationship between the hippocampus and antipsychotics.
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http://dx.doi.org/10.1016/j.bbr.2021.113126DOI Listing
April 2021

Effects of repeated electroconvulsive shocks on dopamine supersensitivity psychosis model rats.

Schizophr Res 2021 02 8;228:1-6. Epub 2021 Jan 8.

Department of Psychiatry, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuou-ku, Chiba, Chiba 260-8670, Japan.

While the long-term administration of antipsychotics is known to cause dopamine supersensitivity psychosis (DSP), recent studies revealed that DSP helps form the foundation of treatment resistance. Electroconvulsive shock (ES) is one of the more effective treatments for treatment-resistant schizophrenia. The objective of this study was to examine whether repeated ES can release rats from dopamine supersensitivity states such as striatal dopamine D2 receptor (DRD2) up-regulation and voluntary hyperlocomotion following chronic administration of haloperidol (HAL). HAL (0.75 mg/kg/day) was administered for 14 days via mini-pumps implanted in rats, and DRD2 density and voluntary locomotion were measured one day after drug cessation to confirm the development of dopamine supersensitivity. The rats with or without dopamine supersensitivity received repeated ES or sham treatments, and then DRD2 density was assessed and a voluntary locomotion test was performed. Chronic treatment with HAL led to the up-regulation of striatal DRD2 and hyperlocomotion in the rats one day after drug cessation. We thus confirmed that these rats experienced a dopamine supersensitivity state. Moreover, after repeated ES, locomotor activity and DRD2 density in the DSP model rats fell to the control level, while an ES sham operation had no effect on the dopamine supersensitivity state. The present study suggests that repeated ES could release DSP model rats from dopamine supersensitivity states. ES may be helpful for patients with DSP.
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http://dx.doi.org/10.1016/j.schres.2020.11.062DOI Listing
February 2021

Association between serum levels of glial cell line-derived neurotrophic factor and inattention in adult patients with attention deficits/hyperactivity disorder.

Psychiatry Res 2021 02 29;296:113674. Epub 2020 Dec 29.

Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan; Department of Child Psychiatry, Chiba University Hospital, Chiba, Japan; Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan.

Glial cell line-derived neurotrophic factor (GDNF) may play an important role in attention. We investigated the association between serum GDNF levels and clinical status in unmedicated adults with attention deficit/hyperactivity disorder (ADHD) (n = 16) and healthy controls (n = 33); the levels were comparable between the ADHD and control groups (107.2 ± 31.7 vs. 110.5 ± 40.0 pg/mL, respectively; p = 0.77). In the ADHD group, higher GDNF serum levels were associated with severe subjective inattention (r = 0.528, p = 0.035). These preliminary results suggest that the serum GDNF level may not be a suitable biomarker for adult ADHD, although it may be associated with the pathophysiology of persistent inattention in adult ADHD.
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http://dx.doi.org/10.1016/j.psychres.2020.113674DOI Listing
February 2021

Platelet-derived growth factor BB: A potential diagnostic blood biomarker for differentiating bipolar disorder from major depressive disorder.

J Psychiatr Res 2021 02 21;134:48-56. Epub 2020 Dec 21.

Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan. Electronic address:

Bipolar disorder (BD) is frequently misdiagnosed as major depressive disorder (MDD) due to overlapping depressive symptoms. This study investigated whether serum platelet-derived growth factor BB (PDGF-BB) is a differential diagnostic biomarker for BD and MDD. An initial SOMAscan proteomics assay of 1311 proteins in small samples from patients with BD and MDD and healthy controls (HCs) suggested that serum levels of PDGF-BB differed between BD and MDD. We then conducted a two-step, exploratory, cross-sectional, case-control study at our institute and five sites that included a total of 549 participants (157 with BD, 144 with MDD, and 248 HCs). Clinical symptoms were assessed using the Hamilton Depression Rating Scale and the Young Mania Rating Scale. In the initial analysis at our institute, serum PDGF-BB levels in the MDD group (n = 36) were significantly lower than those in the BD (n = 39) and HC groups (n = 36). In the multicenter study, serum PDGF-BB levels in the MDD group were again significantly lower than those in the BD and HC groups, with no significant difference between the BD and HC groups. Treatment with sodium valproate was associated with significantly lower serum PDGF-BB levels in patients with BD. After controlling for confounding factors (sex, age, body mass index, clinical severity, and valproate medication), serum PDGF-BB levels were lower in the MDD group than in the BD group regardless of mood state. Our findings suggest that serum PDGF-BB may be a potential biomarker to differentiate BD and MDD.
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http://dx.doi.org/10.1016/j.jpsychires.2020.12.051DOI Listing
February 2021

Astroglial glutamate transporter 1 and glutamine synthetase of the nucleus accumbens are involved in the antidepressant-like effects of allopregnanolone in learned helplessness rats.

Behav Brain Res 2021 03 28;401:113092. Epub 2020 Dec 28.

Department of Psychiatry, Chiba University Graduate School of Medicine, 1-8-1 Inohana Chuou-ku, Chiba, Chiba, 260-8670, Japan.

Clinical studies have demonstrated that allopregnanolone (3α5α-tetrahydroprogesterone, ALLO) has antidepressant-like effects on patients with depression. Previous studies have shown alteration of the astroglial glutamate transporter-1 (GLT-1) and glutamine synthetase (GS) in depression, and ALLO is known to modulate glutamate release. The present study aimed to investigate whether astroglial GLT-1 and GS are indeed involved in the antidepressant-like effects of ALLO in learned helplessness (LH) rats, a validated animal model of depression. The results of this study showed that bilateral microinjection of ALLO into the lateral ventricles could normalize the levels of GLT-1 and GS in the nucleus accumbens (NAc) and of GS in the hippocampal CA1 region of LH rats. These results suggest a certain connection between the antidepressant-like effects of ALLO and the astroglial GLT-1/GS system of the NAc in LH rats.
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http://dx.doi.org/10.1016/j.bbr.2020.113092DOI Listing
March 2021

Genetic association study detected misalignment in previous whole exome sequence: association study of ZNF806 and SART3 in tardive dystonia.

Psychiatr Genet 2021 02;31(1):29-31

Department of Psychiatry, Chiba University Graduate School of Medicine.

Tardive dystonia is one of the most serious types of extrapyramidal symptoms that antipsychotics can cause. There is no established treatment to relieve this symptom, and its etiology is unclear. Recently, we identified very rare single-nucleotide polymorphisms (SNPs) on ZNF806 and SART3 by exome sequencing in three patients with profoundly severe tardive dystonia. Here, we conducted an association study (case, N = 16 vs. control, N = 96) on the rarest SNP selected from each gene. The results showed that rs2287546 on SART3 was not related to tardive dystonia and that rs4953961 on ZNF806 was a heterozygote in all the subjects, implying the absence of a rare SNP in this locus. We found three other genomic regions with high similarity to the relevant region on ZNF806 by BLAT searches. This strongly suggested a misalignment error in this region in our previous exome sequence. In conclusion, ZNF806 and SART3 are unlikely to be related to tardive dystonia.
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http://dx.doi.org/10.1097/YPG.0000000000000263DOI Listing
February 2021

A randomized-controlled trial of blonanserin and olanzapine as adjunct to antipsychotics in the treatment of patients with schizophrenia and dopamine supersensitivity psychosis: The ROADS study.

Asian J Psychiatr 2020 Oct 31;53:102369. Epub 2020 Aug 31.

Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan; Child Psychiatry, Chiba University Hospital, Chiba, Japan; Division of Medical Treatment and Rehabilitation, Center for Forensic Mental Health, Chiba University, Chiba, Japan.

Dopamine supersensitivity psychosis (DSP) is a key factor contributing to the development of antipsychotic treatment-resistant schizophrenia. We examined the efficacy and safety of blonanserin (BNS) and olanzapine (OLZ) as adjuncts to prior antipsychotic treatment in patients with schizophrenia and DSP in a 24-week, multicenter (17 sites), randomized, rater-blinded study with two parallel groups (BNS and OLZ add-on treatments) in patients with schizophrenia and DSP: the ROADS Study. The primary outcome was the change in the Positive and Negative Syndrome Scale (PANSS) total score from baseline to week 24. Secondary outcomes were changes in the PANSS subscale scores, Clinical Global Impressions, and Extrapyramidal Symptom Rating Scale (ESRS), and changes in antipsychotic doses. The 61 assessed patients were allocated into a BNS group (n = 26) and an OLZ group (n = 29). The PANSS total scores were reduced in both groups (mean ± SD: -14.8 ± 24.0, p = 0.0042; -10.5 ± 12.9, p = 0.0003; respectively) with no significant between-group difference (mean, -4.3, 95 %CI 15.1-6.4, p = 0.42). The BNS group showed significant reductions from week 4; the OLZ group showed significant reductions from week 8. The ESRS scores were reduced in the BNS group and the others were reduced in both groups. The antipsychotic monotherapy rates at the endpoint were 26.3 % (n = 6) for BNS and 23.8 % (n = 5) for OLZ. The concomitant antipsychotic doses were reduced in both groups with good tolerability. Our results suggest that augmentations with BNS and OLZ are antipsychotic treatment options for DSP patients, and BNS may be favorable for DSP based on the relatively quick responses to BNS observed herein.
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http://dx.doi.org/10.1016/j.ajp.2020.102369DOI Listing
October 2020

The effectiveness of very slow switching to aripiprazole in schizophrenia patients with dopamine supersensitivity psychosis: a case series from an open study.

Int Clin Psychopharmacol 2020 11;35(6):338-344

Department of Psychiatry, Chiba University Graduate School of Medicine.

Dopamine supersensitivity psychosis (DSP) in patients with schizophrenia is induced by treatment with a high dosage of antipsychotics for a long time period, and it is characterized by unstable psychotic symptoms. The upregulation of dopamine D2 receptor (DRD2) provoked by antipsychotics underlies DSP. Aripiprazole does not cause an excessive blockade of DRD2 and is less likely to upregulate DRD2 by aripiprazole's dopamine partial agonistic profile. Aripiprazole; however, has a potential risk of inducing severe rebound psychosis in patients who have already developed dopamine supersensitivity. Recently, an animal model study suggested that aripiprazole could attenuate established dopamine supersensitivity. The present study was conducted to examine whether very slowly switching to aripiprazole could help patients with schizophrenia with dopamine supersensitivity while avoiding rebound psychosis. This study was a single-armed and open-labeled study in which patients were observed over a period of 2 years. Only 11 patients were ultimately recruited. Five patients were successfully switched to a sufficient dose of aripiprazole and completed the study protocol. These five patients did not present with severe DSP over the study period, but only one patient showed a large improvement in psychopathology. Five patients dropped out of the study, and one of these five showed a severe worsening of psychosis. The present study indicated that the introduction of aripiprazole in patients with DSP was difficult, but suggested that aripiprazole could contribute to attaining a stable state in psychosis if it was applied with careful observation.
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http://dx.doi.org/10.1097/YIC.0000000000000322DOI Listing
November 2020

Relationship between perception and anxiety about COVID-19 infection and risk behaviors for spreading infection: A national survey in Japan.

Brain Behav Immun Health 2020 Jul 2;6:100101. Epub 2020 Jul 2.

Center for Forensic Mental Health, Chiba University, Japan.

Background: The novel corona virus infection (COVID-19) quickly became a pandemic state. Identifying characteristics of "possible super spreaders", suggested as a dominant cause of rapid spreading transmission, will help us to design proper prevention strategies.

Methods: We conducted a nation-wide online survey to investigate the relationship of perception and anxiety levels about COVID-19 to the possible risk behaviors for spread of the virus in Japan. We recruited a total of 4,000 citizens, who responded to the questionnaire including several questions regarding the level of fear and anxiety about COVID-19, infection preventive behaviors and access to media with trust level about the virus as well as some demographic and socioeconomic data during March 27th and 28th, 2020.

Findings: Thirteen-point-three percent of the participants rated "1" on a nine-point Likert with respect to the knowledge about COVID-19. Ten-point-one percent and 11.7% presented no anxiety of being infected and transmission to others. Ten-point-eight percent showed no worry about symptomatic aggravation. Eight-point-one percent had no serious concern about expanding infection. The distribution of these items was highly correlated with each other. Participants with the low level of knowledge about COVID-19 were likely to less frequently access any information sources and neither trust them. They were less anxious about their health status, and less likely to put precautionary behaviors such as washing hands and avoiding crowded spaces, suggested by statistical analyses.

Interpretation: The present study suggests that it is greatly important to enlighten those have no concerns about this crisis of COVID-19 and modify their risk behavior via various ways, in order to prevent and control this viral pandemic.

Funding: This study was funded by the management grand provided to Chiba University Graduate School of Medicine and the Japan Society for the Promotion of Science KAKENHI grants.
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http://dx.doi.org/10.1016/j.bbih.2020.100101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7331545PMC
July 2020

Autistic traits and cognitive profiles of treatment-resistant schizophrenia.

Schizophr Res Cogn 2020 Dec 27;22:100186. Epub 2020 Jul 27.

Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan.

The complex pathophysiology of treatment-resistant schizophrenia (TRS) includes severe positive symptoms but also other symptom domains. The overlapping psychological profiles of schizophrenia and autistic spectrum disorder (ASD) are not established. We compared TRS patients (n = 30) with schizophrenia patients in remission (RemSZ, n = 28) and ASD patients (n = 28), focusing on both neurodevelopmental aspects and general and social cognitive impairments. The TRS group performed the worst on general neurocognition (measured by the MATRICS Consensus Cognitive Battery) and social cognition (measured by the theory of mind and emotional expression). The RemSZ group performed the best among the three groups. Regarding autistic traits, all measurements by the Autism-Spectrum Quotient/Autism Screening Questionnaire/Pervasive Developmental Disorder Assessment Rating Scale showed that (1) the ASD patients had the highest autistic traits (2) the TRS patients' scores were less severe than the ASD group's, but (3) the overall trends placed the TRS group between the ASD and the RemSZ group. These findings indicate that TRS patients and remitted patients could have distinctive neurodevelopmental and cognitive profiles. Further, the degrees of social cognitive dysfunction and autistic traits in TRS patients could be close to those of ASD patients, suggesting similarities between TRS and ASD.
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http://dx.doi.org/10.1016/j.scog.2020.100186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7390750PMC
December 2020

Inter-agency collaboration factors affecting multidisciplinary workers' ability to identify child maltreatment.

BMC Res Notes 2020 Jul 6;13(1):323. Epub 2020 Jul 6.

Department of Psychiatry, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuou-ku, Chiba, Chiba, 260-8670, Japan.

Objectives: This study aimed to clarify the factors of successful inter-agency collaboration that affect multidisciplinary workers' abilities to identify child maltreatment. A questionnaire-based survey was conducted; the contents of the questionnaire included the Collaboration Evaluation Scale we developed and the workers' abilities to identify child maltreatment. In total, 277 individuals from various agencies in Japan participated in this study. To examine the factors of successful inter-agency collaboration affecting workers' awareness of child maltreatment, we used hierarchical multiple regression analysis.

Results: The analysis showed the positive effect of "commitment with loyalty" on the workers' awareness of child maltreatment-related information in all fields (β = .18-.31, p < .05), the effect of "strong leadership" on information about maltreated children and the home environment (β = .18, p < .05; β = .16, p < .05, respectively), and the effect of "resources" on the information about mothers' information during pregnancy and of fathers' feelings towards their children during the perinatal period (β = .17, p < .05; β = .22, p < .01, respectively). In conclusion, commitment with loyalty, strong leadership, and resources are factors of successful inter-agency collaboration that affects the ability of multidisciplinary workers to recognize signs of child maltreatment.
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http://dx.doi.org/10.1186/s13104-020-05162-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7339586PMC
July 2020

Genetic risks of schizophrenia identified in a matched case-control study.

Eur Arch Psychiatry Clin Neurosci 2021 Jun 4;271(4):775-781. Epub 2020 Jul 4.

Department of Psychiatry, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuou-ku, Chiba, Chiba, 260-8670, Japan.

It has been suggested that dopaminergic neurotransmission plays important roles for the psychotic symptoms and probably etiology of schizophrenia. In our recent preliminary study, we demonstrated that the specific allele combinations of dopamine-related functional single nucleotide polymorphisms (SNPs), rs10770141, rs4680, and rs1800497 could indicate risks for schizophrenia. The present validation study involved a total of 2542 individuals who were age- and sex-matched in a propensity score matching analysis, and the results supported the statistical significances of the proposed genetic risks described in our previous reports. The estimated odds ratios were 1.24 (95% CI 1.06-1.45, p < 0.001) for rs4680, 1.73 (95% CI 1.47-2.02, p < 0.0001) for rs1800497, and 1.79 (95% CI 1.35-2.36, p < 0.0001) for rs10770141. A significant relationship was also revealed among these three polymorphisms and schizophrenia, with corresponding coefficients (p < 0.0001). In this study, we also present a new scoring model for the identification of individuals with the disease risks. Using the cut-off value of 2, our model exhibited sensitivity for almost two-thirds of all of the schizophrenia patients: odds ratio 1.87, 95% CI 1.59-2.19, p < 0.0001. In conclusion, we identified significant associations of dopamine-related genetic combinations with schizophrenia. These findings suggest that some types of dopaminergic neurotransmission play important roles for development of schizophrenia, and this type of approach may also be applicable for other multifactorial diseases, providing a potent new risk predictor.
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http://dx.doi.org/10.1007/s00406-020-01158-3DOI Listing
June 2021

Successful rechallenge with paliperidone after clozapine treatment for a patient with dopamine supersensitivity psychosis.

SAGE Open Med Case Rep 2020 7;8:2050313X20929561. Epub 2020 Jun 7.

Department of Psychiatry, Graduate School of Medicine, Chiba University, Chiba, Japan.

We describe the case of a 49-year-old Japanese male patient successfully treated with a paliperidone rechallenge following 2-year treatment with clozapine for treatment-resistant schizophrenia. He had responded well to conventional antipsychotic treatment for the initial psychotic episode but gradually developed dopamine supersensitivity; even treatment with paliperidone and another antipsychotic medication (a total up to 1700 mg in chlorpromazine-equivalent dose) had not improved his psychotic symptoms. Clozapine treatment produced temporary symptomatic relief, but the clozapine dose could not be increased to > 150 mg due to the patient's intolerance. Following low-dose clozapine treatment for 2 years, a rechallenge with paliperidone monotherapy ameliorated his psychotic symptoms. This suggests that clozapine may have the potential to release the dopamine supersensitivity state. Our patient's case indicates that for patients with dopamine supersensitivity psychosis, a rechallenge with a previously ineffective antipsychotic after clozapine treatment may be successful.
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http://dx.doi.org/10.1177/2050313X20929561DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278325PMC
June 2020
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