BackgroundsHikikomori, pathological social withdrawal, is becoming a crucial mental health issue in Japan and worldwide. We have developed a 3-day family intervention program for hikikomori sufferers based on Mental Health First Aid... more
BackgroundsHikikomori, pathological social withdrawal, is becoming a crucial mental health issue in Japan and worldwide. We have developed a 3-day family intervention program for hikikomori sufferers based on Mental Health First Aid (MHFA) and Community Reinforcement and Family Training (CRAFT). This study aims to confirm the effectiveness of the 3-day program by a randomized controlled trial.MethodsThis study was registered on the UMIN Clinical Trials Registry (UMIN000037289). Fifteen parents were assigned to the treat as usual (TAU) group (TAU only; Age Mean, 65.6; SD, 7.8), and 14 to the Program group (program + TAU; Age Mean, 67.9; SD, 8.6). This study was discontinued due to the COVID-19 pandemic; the recruitment rate was 36.3% of our target sample size of 80.ResultsPerceived skills improved temporally and stigma temporally worsened in the TAU group. Confidence decreased and attitude showed no change in both groups. Aggressive behaviors of hikikomori sufferers were significantl...
The global pandemic of COVID-19 has forced people to restrict their outings. In Japan, self-restraint behavior (SRB) has been requested by the government, and some of those decreasing their outings may shift to pathological social... more
The global pandemic of COVID-19 has forced people to restrict their outings. In Japan, self-restraint behavior (SRB) has been requested by the government, and some of those decreasing their outings may shift to pathological social withdrawal; hikikomori. The purpose of this study was to examine the risk factors of hikikomori conducting an online prospective survey. An online survey was conducted in June 2020 and December 2020; (1) SRB-related indicators (degree of SRB, motivation for SRB, stigma and self-stigma toward COVID-19, anxiety and depressive feelings toward COVID-19) and (2) general mental health (hikikomori tendency, depressive symptoms, modern type depression (MTD) tendency, internet addiction) were collected. A cross-lagged effects model was performed to examine the association between these variables. Lack of emotional support and lack of socialization in June 2020 increased isolation in December 2020. Besides, MTD and hikikomori interacted with each other. Interestingl...
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Direct conversion techniques, which generate induced-neuronal (iN) cells from human fibroblasts in less than two weeks, are expected to discover unknown neuronal phenotypes of neuropsychiatric disorders. Here, we present unique gene... more
Direct conversion techniques, which generate induced-neuronal (iN) cells from human fibroblasts in less than two weeks, are expected to discover unknown neuronal phenotypes of neuropsychiatric disorders. Here, we present unique gene expression and cell morphology profiles in iN cells derived from neurofibromatosis type 1 (NF1) patients. NF1 is a single-gene multifaceted disorder with relatively high co-occurrence of autism spectrum disorder (ASD). Adenylyl cyclase (AC) dysfunction is one of the candidate pathways in abnormal neuronal development in the brains of NF1 patients. In our study, microarray-based transcriptomic analysis of iN cells from healthy controls (males) and NF1 patients (males) revealed significantly different gene expression of 149 (110 were upregulated and 39 were downregulated). In iN cells derived from NF1 patients (NF1-iN cells), there was a change in the expression level of 90 genes with the addition of forskolin, an AC activator. Furthermore, treatment with ...
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BackgroundModern-Type Depression (MTD) is a category of depression that has been studied mainly in Japan; however, no study has attempted to determine its relation to chronic pain.AimTo determine possible associations between... more
BackgroundModern-Type Depression (MTD) is a category of depression that has been studied mainly in Japan; however, no study has attempted to determine its relation to chronic pain.AimTo determine possible associations between psychological traits related to MTD and the chronic pain of patients at psychiatric clinics.MethodTwo hundred and twenty-one first time patients who visited the psychiatric clinic at a Japanese university medical center or an associated clinic were enrolled. The Hamilton Depression Rating Scale was used to measure depressive symptoms. The 22-item Tarumi's Modern-Type Depression Trait Scale (TACS-22), Achievement Motive, and 20-item Toronto Alexithymia Scale were used to assess psychological traits related to depression and chronic pain. The clinical diagnosis of each patient was confirmed by use of the Structured Clinical Interview for DSM-IV Axis I Disorders, administered by experienced specialists. The medians of the psychological traits identified were c...
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Lower serum levels of low-density lipoprotein cholesterol (LDL-C) have been suggested to indicate higher suicide risk and various psychiatric symptoms. Previously, we reported that lower serum LDL-C levels are associated with loneliness,... more
Lower serum levels of low-density lipoprotein cholesterol (LDL-C) have been suggested to indicate higher suicide risk and various psychiatric symptoms. Previously, we reported that lower serum LDL-C levels are associated with loneliness, social phobia, isolated life with little social support, and lower trust in others among young non-clinical females. Thus, we hypothesize that schizoid personality traits may be associated with lower serum LDL-C. We here verified this hypothesis using non-clinical data and clinical data with schizophrenia. Using the database from the Midlife in Japan (MIDJA), a cohort of residents living in Tokyo, we analyzed whether schizoid-related interpersonal characteristics were associated with LDL-C. In addition, we assessed the association between blood biomarkers including LDL-C and schizoid personality traits in 101 adult non-clinical volunteers. Finally, we evaluated the interaction between LDL-C and social decision making of patients with schizophrenia. ...
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Many birds initiate incubation before clutch completion which results in asymmetric survival of eggs and nestlings within the clutch. When parents start incubating before clutch completion, low survival is expected of the nestlings... more
Many birds initiate incubation before clutch completion which results in asymmetric survival of eggs and nestlings within the clutch. When parents start incubating before clutch completion, low survival is expected of the nestlings hatched from eggs laid after the onset of incubation due to hatching asynchrony. Conversely, eggs laid before the onset of incubation may have a lower survival because of extrinsic factors (e.g. ambient temperature and microbial infection). Many studies investigating the allocation of parental investment have hypothesized two different strategies wherein parents allocate investment that favors eggs/nestlings with high survival prospects or compensates for the disadvantages of eggs/nestlings with low survival prospects. Although birds could take different strategies based on incubation onset within the same breeding attempt, this idea has never been tested. We conducted an observational study to investigate the effects of incubation onset on the survival o...
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Objective Recently, rational polypharmacy approaches have been proposed, regardless of the lower risk and cost of monotherapy. Considering monotherapy as first-line treatment and polypharmacy as rational treatment, a balanced attitude... more
Objective Recently, rational polypharmacy approaches have been proposed, regardless of the lower risk and cost of monotherapy. Considering monotherapy as first-line treatment and polypharmacy as rational treatment, a balanced attitude toward polypharmacy is recommended. However, the high prevalence of polypharmacy led the Japanese government to establish a polypharmacy reduction policy. Based on this, the association between the policy and psychiatrists’ attitude toward polypharmacy has been under debate.Methods We developed an original questionnaire about Psychiatrists’ attitudes toward polypharmacy (PAP). We compared the PAP scores with the treatment decision-making in clinical case vignettes. Multiple regression analyses were performed to quantify associations of explanatory variables including policy factors and PAP scores. The anonymous questionnaires were administered to psychiatrists worldwide.Results The study included 347 psychiatrists from 34 countries. Decision-making tow...
Research Interests: Medicine and Polypharmacy
Background: The COVID-19 pandemic has forced people to change their lifestyles, especially with respect to restrictions on going out. Forced quarantine (i.e., lockdown) and self-restraint behavior (SRB), including self-quarantine, are... more
Background: The COVID-19 pandemic has forced people to change their lifestyles, especially with respect to restrictions on going out. Forced quarantine (i.e., lockdown) and self-restraint behavior (SRB), including self-quarantine, are suggested to induce potential negative impacts on public mental health. SRB seems to be related to governmental policies, each individual’s social background and mental condition; however, no empirical studies have been conducted. Methods: 1053 participants (mainly office workers) from epidemic areas and non-epidemic areas in Japan voluntarily conducted an online survey in June 2020. We assessed COVID-19-related aspects such as the degree of SRB, motivation for SRB, stigma, anxiety and depressive feelings due to COVID-19 by original questionnaires) and general mental health status (social anxiety by MINI-SPIN, depressive tendency by PHQ-9, depression-related personality traits by TACS-22 and resilience by TRS). Results: Regional comparison showed signi...
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Microglia are resident innate immune cells which release many factors including proinflammatory cytokines or nitric oxide (NO) when they are activated in response to immunological stimuli. Pathophysiology of Alzheimer's disease (AD)... more
Microglia are resident innate immune cells which release many factors including proinflammatory cytokines or nitric oxide (NO) when they are activated in response to immunological stimuli. Pathophysiology of Alzheimer's disease (AD) is related to the inflammatory responses mediated by microglia. Intracellular Casignaling is important for microglial functions such as release of NO and cytokines. In addition, alteration of intracellular Casignaling underlies the pathophysiology of AD, while it remains unclear how donepezil, an acetylcholinesterase inhibitor, affects intracellular Camobilization in microglial cells. We examined whether pretreatment with donepezil affects the intracellular Camobilization using fura-2 imaging and tested the effects of donepezil on phagocytic activity by phagocytosis assay in rodent microglial cells. In this study, we observed that pretreatment with donepezil suppressed the TNFα-induced sustained intracellular Caelevation in both rat HAPI and mouse pr...
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Sex allocation theory predicts that parents bias the offspring sex ratio strategically. In avian species, the offspring sex ratio can be biased at multiple growth stages, although the mechanisms are not well known. It is crucial to reveal... more
Sex allocation theory predicts that parents bias the offspring sex ratio strategically. In avian species, the offspring sex ratio can be biased at multiple growth stages, although the mechanisms are not well known. It is crucial to reveal a cause and timing of biased offspring sex ratio. We investigated (i) offspring sex ratio at multiple growth stages, from laying to fledging; and (ii) the stage at which offspring sex ratio became biased; and (iii) the cause of biased offspring sex ratio in Eurasian tree sparrows. Sex determination of 218 offspring, including hatchlings and unhatched eggs from 41 clutches, suggested that the offspring sex ratio was not biased at the egg-laying stage but was significantly female-biased after the laying stage due to higher mortality of male embryos. Half of the unhatched eggs showed no sign of embryo development (37/74, 50.00%), and most undeveloped eggs were male (36/37, 97.30%). Additional experiments using an incubator suggested that the cause of ...
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Early intervention in depression has been critical to prevent its negative impact including suicide. Recent blood biomarker studies for major depressive disorder (MDD) have suggested that tryptophan-kynurenine and lipid related... more
Early intervention in depression has been critical to prevent its negative impact including suicide. Recent blood biomarker studies for major depressive disorder (MDD) have suggested that tryptophan-kynurenine and lipid related metabolites are involved in the pathophysiology of MDD. However, there have been limited studies investigating these blood biomarkers in first-episode drug-naïve MDD, which are particularly important for early intervention in depression. As an exploratory pilot case-control study, we examined the above blood biomarkers, and analyzed how these biomarkers are associated with clinical variables in first-episode drug-naïve MDD patients, based on metabolome/lipidome analysis. Plasma tryptophan and kynurenine levels were significantly lower in MDD group (N = 15) compared to healthy controls (HC) group (N = 19), and plasma tryptophan was the significant biomarker to identify MDD group (area under the curve = 0.740). Lower serum high density lipoprotein-cholesterol (...
Research Interests: Biomarkers, Medicine, Lipids, Prospective studies, Humans, and 15 moreInternal Medicine, Affective Disorders, Major Depressive Disorder, Female, Male, Middle Aged, Biomarker, Adult, Kynurenine pathway, Pilot Projects, Predictive value of tests, Case Control Studies, Severity of Illness Index, Psychology and Cognitive Sciences, and Medical and Health Sciences
Advance in the exome-wide sequencing analysis contributes to identifying hundreds of genes that are associated with early-onset epileptic encephalopathy and neurodevelopmental disorders. On the basis of massive sequencing data, functional... more
Advance in the exome-wide sequencing analysis contributes to identifying hundreds of genes that are associated with early-onset epileptic encephalopathy and neurodevelopmental disorders. On the basis of massive sequencing data, functional interactions among different genes are suggested to explain the common molecular pathway underlying the pathogenic process of these disorders. However, the relevance of such interactions with the phenotypic severity or variety in an affected individual remains elusive. In this report, we present a 45-year-old woman with neurofibromatosis type 1 (NF1), infantile-onset epileptic encephalopathy, and severe developmental delay. Whole-exome sequencing identified de novo pathogenic mutations inand the Schaaf-Yang syndrome-associated gene,. Literature-curated interaction data predicted that NF1 and MAGEL2 proteins were closely connected in this network via their common interacting proteins. Direct conversion of fibroblasts into neurons in vitro showed tha...
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Microglia-immune cells in the brain-have recently been highlighted to understand the pathophysiology of psychiatric disorders such as schizophrenia, depression, and autism. In this review paper, we introduce the microglia hypothesis for... more
Microglia-immune cells in the brain-have recently been highlighted to understand the pathophysiology of psychiatric disorders such as schizophrenia, depression, and autism. In this review paper, we introduce the microglia hypothesis for psychiatric disorders. In addition, we introduce our novel translational research approach to psychiatric disorders using microglia-like (iMG) cells directly induced from human blood, these iMG cells can be produced from peripheral monocytes within two weeks using two cytokines: granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-34 (IL-34).
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Evaluating the severity of depression (SOD), especially suicidal ideation (SI), is crucial in the treatment of not only patients with mood disorders but also psychiatric patients in general. SOD has been assessed on interviews such as the... more
Evaluating the severity of depression (SOD), especially suicidal ideation (SI), is crucial in the treatment of not only patients with mood disorders but also psychiatric patients in general. SOD has been assessed on interviews such as the Hamilton Rating Scale for Depression (HAMD)-17, and/or self-administered questionnaires such as the Patient Health Questionnaire (PHQ)-9. However, these evaluation systems have relied on a person's subjective information, which sometimes lead to difficulties in clinical settings. To resolve this limitation, a more objective SOD evaluation system is needed. Herein, we collected clinical data including HAMD-17/PHQ-9 and blood plasma of psychiatric patients from three independent clinical centers. We performed metabolome analysis of blood plasma using liquid chromatography mass spectrometry (LC-MS), and 123 metabolites were detected. Interestingly, five plasma metabolites (3-hydroxybutyrate (3HB), betaine, citrate, creatinine, and gamma-aminobutyr...
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Several studies have revealed that neuregulins (NRGs) are involved in brain function and psychiatric disorders. While NRGs have been regarded as neuron- or astrocyte-derived molecules, our research has revealed that microglia also express... more
Several studies have revealed that neuregulins (NRGs) are involved in brain function and psychiatric disorders. While NRGs have been regarded as neuron- or astrocyte-derived molecules, our research has revealed that microglia also express NRGs, levels of which are markedly increased in activated microglia. Previous studies have indicated that microglia are activated in the brains of individuals with autism spectrum disorder (ASD). Therefore, we investigated microglial NRG mRNA expression in multiple lines of mice considered models of ASD. Intriguingly, microglial NRG expression significantly increased in BTBR and socially-isolated mice, while maternal immune activation (MIA) mice exhibited identical NRG expression to controls. Furthermore, we observed a positive correlation between NRG expression in microglia and peripheral blood mononuclear cells (PBMCs) in mice, suggesting that NRG expression in human PBMCs may mirror microglia-derived NRG expression in the human brain. To transla...
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The pathophysiology of bipolar disorder, especially the underlying mechanisms of the bipolarity between manic and depressive states, has yet to be clarified. Microglia, immune cells in the brain, play important roles in the process of... more
The pathophysiology of bipolar disorder, especially the underlying mechanisms of the bipolarity between manic and depressive states, has yet to be clarified. Microglia, immune cells in the brain, play important roles in the process of brain inflammation, and recent positron emission tomography studies have indicated microglial overactivation in the brain of patients with bipolar disorder. We have recently developed a technique to induced microglia-like (iMG) cells from peripheral blood (monocytes). We introduce a novel translational approach focusing on bipolar disorder using this iMG technique. We hypothesize that immunological conditional changes in microglia may contribute to the shift between manic and depressive states, and thus we herein analyzed gene profiling patterns of iMG cells from three patients with rapid cycling bipolar disorder during both manic and depressive states, respectively. We revealed that the gene profiling patterns are different between manic and depressiv...
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Internet addiction (IA), also referred to as internet use disorder, is a serious problem all over the world, especially in Asian countries. Severe IA in students may be linked to academic failure, Attention Deficit Hyperactivity Disorder... more
Internet addiction (IA), also referred to as internet use disorder, is a serious problem all over the world, especially in Asian countries. Severe IA in students may be linked to academic failure, Attention Deficit Hyperactivity Disorder (ADHD), and forms of social withdrawal such as hikikomori. In this study, we performed a survey to investigate the relation between IA and ADHD symptoms among college students. Severity of IA and ADHD traits were assessed by self-report scales. Subjects were 403 college students (response rate 78%) who completed a questionnaire including the Young's Internet Addiction Test (IAT) and Adult ADHD Self-Report Scale (ASRS)-V1.1. Out of 403 subjects, 165 were male, mean age was 18.4 ± 1.2 yrs, and mean total IAT score was 45.2 ± 12.6. One hundred forty-eight respondents (36.7%) were average internet users (IAT <40), 240 (59.6%) had possible addiction (IAT 40 to 69), and 15 (3.7%) had severe addiction (IAT 70 and higher). Mean length of internet use...
Research Interests: Clinical Psychology, Cognitive Science, Addiction, Japan, Adolescent, and 15 moreMedicine, Comorbidity, Internet Addiction, Humans, Female, Male, Hikikomori, Neurodevelopmental Disorders, Clinical Sciences, Adult, Attention Deficit, Internet, Attention deficit disorder with hyperactivity, Attention deficit hyperactivity disorder, and Internet Use Disorder
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Cushing's syndrome (CS) is a rare disorder, especially in older people. Loss of brain volume and neurocognitive impairment of varying degrees has been demonstrated in patients with CS. However, there is a large difference between the... more
Cushing's syndrome (CS) is a rare disorder, especially in older people. Loss of brain volume and neurocognitive impairment of varying degrees has been demonstrated in patients with CS. However, there is a large difference between the median age of presentation of CS and that of Alzheimer's disease. We herein report a case of a patient with Alzheimer's disease complicated by elderly-onset CS who had undergone surgical treatment for adrenal hyperplasia. Surgical correction of hypercortisolism seems to have slowed the progression of brain volume loss and cognitive dysfunction and improved psychiatric symptoms such as visual hallucination, restlessness, and psychomotor excitement. These improvements have remarkably reduced the burden on the patient's caregivers. The present case suggests that subclinical CS may be present, particularly in rapidly progressive dementia, and that surgical treatment of CS for neuropsychiatric symptoms is useful.
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Suicide has been a leading cause of death among Japanese college and university students. Gatekeeper-training programs have been shown to improve detection and referral of individuals who are at risk of suicide by training non-mental... more
Suicide has been a leading cause of death among Japanese college and university students. Gatekeeper-training programs have been shown to improve detection and referral of individuals who are at risk of suicide by training non-mental health professional persons, but no study have investigated effectiveness of such programs in university settings in Japan. The aim of this study is to investigate the effectiveness of gatekeeper-training program for administrative staff in Japanese universities. We developed a 2.5 hours gatekeeper-training program based on the Mental Health First Aid program, which was originally developed for the general public. Seventy-six administrative staff in Hokkaido University participated in the program. Competence and confidence in managing suicide intervention, behavioral intention as a gatekeeper and attitude while handling suicidal students were measured by a self-reported questionnaire before, immediately after and a month after the program. We found a si...
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Japan's prototype of depression had traditionally been a melancholic depression based on the premorbid personality "shūchaku-kishitsu" proposed by Mitsuzo Shimoda in the 1930s. However since around 2000, a novel form of... more
Japan's prototype of depression had traditionally been a melancholic depression based on the premorbid personality "shūchaku-kishitsu" proposed by Mitsuzo Shimoda in the 1930s. However since around 2000, a novel form of depression has emerged among youth. Called 'modern type depression (MTD)' by mass media, the term has quickly gained popularity among the general public, though it has not been regarded as an official medical term. Likewise, lack of consensus guidelines for its diagnosis and treatment, and a dearth of scientific literature on MTD has led to confusion when dealing with it in clinical practice in Japan. In this review article, we summarize and discuss the present situation and issues regarding MTD by focusing on historical, diagnostic, psychosocial, and cultural perspectives. We also draw on international perspectives (Kato TA et al. J Affect Dis 2011) that begin to suggest that MTD is a phenomenon that MTD may exist not only in Japan but also in ...
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Chronic kidney disease (CKD) is a substantial public health problem. In the United States, almost 8% of the population has CKD and 571,000 patients receive treatment for endstage renal disease. Although the incidence of CKD is increasing... more
Chronic kidney disease (CKD) is a substantial public health problem. In the United States, almost 8% of the population has CKD and 571,000 patients receive treatment for endstage renal disease. Although the incidence of CKD is increasing in all age groups, this is particularly true in the elderly. There is a greater risk of developing neurocognitive disorders and dementia in older adults, and amajor determinant of quality of life in the elderly is the level of cognitive function. Recent data in this regard suggest that in individuals at all stages of CKD, theremay be a higher risk of developing dementia and cognitive impairment than in those without CKD. Given the increase in life expectancy and the aging of the population in industrialized countries, the neurocognitive disorder burden associated with CKD is expected to worsen. Up to 70% of patients undergoing hemodialysis who are 55 years and older have moderate to severe chronic cognitive impairment, yet it is largely undiagnosed. Dementia is associated with high risks of death, dialysis withdrawal, hospitalization, and disability among patients with endstage renal disease. We describe the case of Ms. A, who is undergoing hemodialysis, in whom various neuropsychiatric symptoms developed, and we review the relevant literature on neurocognitive disorders in CKD. University, Saga, Japan (HT, TH, JM, YH, YM, TK, AM); Department of Radiology, Faculty of Medicine, Saga University, Saga, Japan (TN); Department of Neuropsychiatry, Graduate School of Medical Sciences, Fukuoka, Japan (TAK). Send correspondence and reprint requests to Hiroshi Tateishi, M.D., and Akira Monji, M.D., Address: 5-1-1 Nabeshima, Saga, Japan; e-mail: muutoyukainanakamatachi@gmail.com, amonji@hf.rim.or.jp & 2016 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved. Case Report
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Schizophrenia is a debilitating mental disorder, affecting more than 30 million people worldwide. As a multifactorial disease, the underlying causes of schizophrenia require analysis by multiplex methods such as proteomics to allow... more
Schizophrenia is a debilitating mental disorder, affecting more than 30 million people worldwide. As a multifactorial disease, the underlying causes of schizophrenia require analysis by multiplex methods such as proteomics to allow identification of whole protein networks. Previous post-mortem proteomic studies on brain tissues from schizophrenia patients have demonstrated changes in activation of glycolytic and energy metabolism pathways. However, it is not known whether these changes occur in neurons or in glial cells. To address this question, we treated neuronal, astrocyte, and oligodendrocyte cell lines with the NMDA receptor antagonist MK-801 and measured the levels of six glycolytic enzymes by Western blot analysis. MK-801 acts on the glutamatergic system and has been proposed as a pharmacological means of modeling schizophrenia. Treatment with MK-801 resulted in significant changes in the levels of glycolytic enzymes in all cell types. Most of the differences were found in o...
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An accumulating body of evidences point to the significance of neuroinflammation and immunogenetics in schizophrenia, characterized by increased serum concentration of several pro-inflammatory cytokines. In the central nervous system... more
An accumulating body of evidences point to the significance of neuroinflammation and immunogenetics in schizophrenia, characterized by increased serum concentration of several pro-inflammatory cytokines. In the central nervous system (CNS), the microglial cells are the major immunocompetent cells which release pro-inflammatory cytokines, nitric oxide (NO) and reactive oxygen species to mediate the inflammatory process. In the present study, we investigated whether or not atypical antipsychotics, namely perospirone, quetiapine and ziprasidone, would have anti-inflammatory effects on the activated microglia which may potentiate neuroprotection. All three atypical antipsychotics significantly inhibited NO generation from activated microglia while perospirone and quetiapine significantly inhibited the TNF-alpha release from activated microglia. Antipsychotics, especially perospirone and quetiapine may have an anti-inflammatory effect via the inhibition of microglial activation, which is...
Research Interests: Pharmacology, Drug interactions, Medicine, Neuroprotection, Mice, and 15 moreNitric oxide, Animals, Neuroinflammation, Microglia, Central Nervous System, Rats, Atypical Antipsychotics, Thiazoles, Cell Survival, Nitrites, Interferon gamma, Antipsychotic agents, Psychology and Cognitive Sciences, Medical and Health Sciences, and Quetiapine
Maladaptive social interaction and its related psychopathology have been highlighted in psychiatry especially among younger generations. In Japan, novel expressive forms of psychiatric phenomena such as "modern-type depression"... more
Maladaptive social interaction and its related psychopathology have been highlighted in psychiatry especially among younger generations. In Japan, novel expressive forms of psychiatric phenomena such as "modern-type depression" and "hikikomori" (a syndrome of severe social withdrawal lasting for at least six months) have been reported especially among young people. Economic games such as the trust game have been utilized to evaluate real-world interpersonal relationships as a novel candidate for psychiatric evaluations. To investigate the relationship between trusting behaviors and various psychometric scales, we conducted a trust game experiment with eighty-one Japanese university students as a pilot study. Participants made a risky financial decision about whether to trust each of 40 photographed partners. Participants then answered a set of questionnaires with seven scales including the Lubben Social Network Scale (LSNS)-6 and the Patient Health Questionnaire ...
Research Interests: Psychology, Clinical Psychology, Interpersonal Communication, Depression, Japan, and 15 moreAdolescent, Medicine, Multidisciplinary, Interpersonal Relationship, Humans, Female, Male, Interpersonal Relations, Hikikomori, PLoS one, Adult, Analysis of Variance, Age Factors, Pilot Projects, and Patient Health Questionnaire
Microglia are resident innate immune cells which release many factors including proinflammatory cytokines, nitric oxide (NO) and neurotrophic factors when they are activated in response to immunological stimuli. Recent reports show that... more
Microglia are resident innate immune cells which release many factors including proinflammatory cytokines, nitric oxide (NO) and neurotrophic factors when they are activated in response to immunological stimuli. Recent reports show that pathophysiology of schizophrenia is related to the inflammatory responses mediated by microglia. Intracellular Ca(2+) signaling, which is mainly controlled by the endoplasmic reticulum (ER), is important for microglial functions such as release of NO and cytokines, migration, ramification and deramification. In addition, alteration of intracellular Ca(2+) signaling underlies the pathophysiology of schizophrenia, while it remains unclear how typical or atypical antipsychotics affect intracellular Ca(2+) mobilization in microglial cells. This mini-review article summarizes recent findings on cellular mechanisms underlying the characteristic differences in the actions of antipsychotics on microglial intracellular Ca(2+) signaling and reinforces the impo...
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While the etiology of schizophrenia remains unclear, there has been a growing amount of evidence pointing to neuroinflammation, which is characterized by an increased serum concentration of several pro-inflammatory cytokines and an... more
While the etiology of schizophrenia remains unclear, there has been a growing amount of evidence pointing to neuroinflammation, which is characterized by an increased serum concentration of several pro-inflammatory cytokines and an increase of microglia in the brain of schizophrenics. Microglia respond rapidly to even minor pathological changes in the brain and may contribute directly to neuronal degeneration by producing various pro-inflammatory cytokines and free radicals. In many aspects, the neuropathology of schizophrenia has recently been reported to be closely associated with microglial activation. Our "Microglia Hypothesis of Schizophrenia" may shed a new light on the therapeutic strategy for schizophrenia.
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Neurons and synapses have long been the dominant focus of neuroscience, thus the pathophysiology of psychiatric disorders has come to be understood within the neuronal doctrine. However, the majority of cells in the brain are not neurons... more
Neurons and synapses have long been the dominant focus of neuroscience, thus the pathophysiology of psychiatric disorders has come to be understood within the neuronal doctrine. However, the majority of cells in the brain are not neurons but glial cells including astrocytes, oligodendrocytes, and microglia. Traditionally, neuroscientists regarded glial functions as simply providing physical support and maintenance for neurons. Thus, in this limited role glia had been long ignored. Recently, glial functions have been gradually investigated, and increasing evidence has suggested that glial cells perform important roles in various brain functions. Digging up the glial functions and further understanding of these crucial cells, and the interaction between neurons and glia may shed new light on clarifying many unknown aspects including the mind-brain gap, and conscious-unconscious relationships. We briefly review the current situation of glial research in the field, and propose a novel t...
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Recent imaging studies have indicated that the pathophysiology of schizophrenia is closely related to white matter abnormalities and microglial activation. Additionally, recent clinical trials have suggested that atypical antipsychotics... more
Recent imaging studies have indicated that the pathophysiology of schizophrenia is closely related to white matter abnormalities and microglial activation. Additionally, recent clinical trials have suggested that atypical antipsychotics may have brain protective properties and that minocycline, an antibiotic with inhibitory effects on microglial activation, improves symptoms of schizophrenia. We have reported that not only atypical antipsychotics with dopamine D2 receptor (D2R) antagonism but also aripiprazole, a unique antipsychotic drug with D2R partial agonism, inhibit microglial activation in vitro. Thus, atypical antipsychotics may exert a beneficial influence on both microglia and oligodendrocytes, while the underlying mechanisms have not been clarified. Here, we investigated whether antipsychotics suppress oligodendrocyte damage by inhibiting microglial activation utilizing a co-culture model with microglia and oligodendrocytes. Pretreatment of aripiprazole and minocycline su...
Research Interests: Pharmacology, Drug interactions, Medicine, Brain, Animals, and 15 moreMicroglia, Quinolones, Haloperidol, Benzoxazoles, Antipsychotic, Minocycline, Cell Survival, Aripiprazole, Nitrites, Interferon gamma, Antipsychotic agents, Psychology and Cognitive Sciences, coculture techniques, Medical and Health Sciences, and Myelin proteolipid protein
The Mental Health First Aid (MHFA) program is a training program for non-health professionals that deals with persons with a mental health crisis (Kitchener & Jorm, 2006). The MHFA-Japan team was established in 2007, and a founding member... more
The Mental Health First Aid (MHFA) program is a training program for non-health professionals that deals with persons with a mental health crisis (Kitchener & Jorm, 2006). The MHFA-Japan team was established in 2007, and a founding member completed a MHFA training program in Melbourne, University of Australia. We consulted with Jorm and Kitchener, and started a Japanese study of the program. Providing the MHFA program for gatekeepers in Japan could help them assess risk factors and refer patients for professional care, and contribute to suicide prevention. Our team cooperated with the gatekeeper training program of the cabinet office of the Japanese government. In addition, this program is applied in instructional activities in the area of the Great East Japan Earthquake.
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Aims. To evaluate the effectiveness of a brief suicide management training programme for Japanese medical residents compared with the usual lecture on suicidality. Methods. In this multi-center, clustered randomized controlled trial, the... more
Aims. To evaluate the effectiveness of a brief suicide management training programme for Japanese medical residents compared with the usual lecture on suicidality. Methods. In this multi-center, clustered randomized controlled trial, the intervention group attended a structured suicide management programme and the control group, the usual lecture on depression and suicidality. The primary outcome was the difference in residents' cumulative competency score to manage suicidal persons from baseline (T0) to 1 month after the intervention (T2), determined using the Suicide Intervention Response Inventory (SIRI-1) score, at individual level. Results. Analysis of 114 residents (intervention group n = 65, control group n = 49) assigned to two clusters in each group revealed no change in SIRI-1 score from T0 to T2 or immediately after the intervention (T1) between the two groups. As a secondary analysis, discrepancy in judgement between the participants and Japanese suicidologists was e...
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An accumulating body of evidence point to the significance of neuroinflammation and immunogenetics also in schizophrenia. Recent genome-wide studies in schizophrenia suggest immune involvement in schizophrenia. Microglia are the resident... more
An accumulating body of evidence point to the significance of neuroinflammation and immunogenetics also in schizophrenia. Recent genome-wide studies in schizophrenia suggest immune involvement in schizophrenia. Microglia are the resident macrophage of the brain and major players in innate immunity in the CNS. They respond rapidly to even minor pathological changes in the brain and may contribute directly to the neuronal degeneration by producing various pro-inflammatory cytokines and free radicals. In many aspects, the neuropathology of schizophrenia is closely associated with microglial activation. We and other researchers have shown the inhibitory effects of some typical or atypical antipsychotics on the release of inflammatory cytokines and free radicals from activated microglia, both of which are not only directly toxic to neurons but also cause a decrease in neurogenesis as well as white matter abnormalities in the brains of the patients with schizophrenia. The treatment throug...
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The new 2 year compulsory residency training program, which includes rotation to each department and requires 1 month of psychiatric training for all residents, started in April 2004 in Japan. In August to September belonging 2008, we... more
The new 2 year compulsory residency training program, which includes rotation to each department and requires 1 month of psychiatric training for all residents, started in April 2004 in Japan. In August to September belonging 2008, we conducted an attitude survey of psychiatrists with 10 or fewer years of experience to 15 institutions to clarify the problems and present condition of primary psychiatric training. Psychiatrists (92%) who experienced the new residency program were satisfied with it, and 41% decided to become a psychiatrist after the primary psychiatric training. We compared the training periods and training institutions. Psychiatrists who experienced training for 3 months or more rate themselves higher with regard to pharmacotherapy, and those who underwent training in private psychiatric hospitals rate themselves higher with regard to their understanding of psychiatric disorders. It was suggested that the introduction of primary psychiatric training has promoted motiv...