Takahiro A. Kato

Kyushu University | Kyudai · Department of Neuropsychiatry, Graduate School of Medical Sciences (Molecular Psychihatry Unit & Mood Disorder Hikikomori Research Clinic)

Mutations in the gene encoding the transient receptor potential vanilloid member 4 (TRPV4), a Ca ²⁺ permeable nonselective cation channel, cause TRPV4‐related disorders. TRPV4 is widely expressed in the brain; however, the pathogenesis underlying TRPV4‐mediated Ca ²⁺ deregulation in neurodevelopment remains unresolved and an effective therapeutic s...

Angiogenic factors associated with Moyamoya disease (MMD) are overexpressed in M2 polarized microglia in ischemic stroke, suggesting that microglia may be involved in the pathophysiology of MMD; however, existing approaches are not applicable to explore this hypothesis. Herein we applied blood induced microglial-like (iMG) cells. We recruited 25 ad...

Microglia play versatile roles in progression of and protection against neuroinflammatory diseases. Little is known, however, about the mechanisms underlying the diverse reactivity of microglia to inflammatory conditions. We investigated how human induced microglia-like (iMG) cells respond to innate immune ligands. Quantitative PCR showed that poly...

Japan witnessed the outbreak of coronavirus disease (COVID-19) in March - May 2020. We examined whether the impact of COVID-19 on people seeking help from mental and physical health professionals varied with changes in employment (from full-time employment to unemployment or leave of absence) and psychological predisposition to new-type depression...

Introduction: A positive association between Internet usage time and Internet addiction among adolescents and adults has been frequently reported; however, studies of working adults focusing on weekdays and holidays are limited. Therefore, this study aimed to elucidate the association between Internet usage time and psychometric tests among working...

Schizophrenia is a psychiatric disorder that affects around 1% of the population in widespread populations, with severe cases leading to long-term hospitalization and necessitation of lifelong treatment. Recent studies on schizophrenia have highlighted the involvement of inflammatory and immunoregulatory mechanisms with the onset of symptoms, and t...

Aims: Hikikomori is a common phenomenon reported in Japan and many other countries. However, the broad trends of the research publications on hikikomori are unclear. Therefore, this study examined the patterns of research on hikikomori using bibliometric analysis. Methods: Relevant publications were searched in Web of Science. Bibliometric analy...

Angiogenic factors associated with Moyamoya disease (MMD) are overexpressed in M2 polarized microglia in ischemic stroke, suggesting that microglia may be involved in the pathophysiology of MMD; however, existing approaches are not applicable to explore this hypothesis. Herein we applied blood induced microglial-like (iMG) cells. We recruited 25 a...

Background: Pharmacoepidemiological studies of clozapine use to treat bipolar disorder (BD), especially in Asia, are rare, although they can provide insights into associated clinical characteristics and support international comparisons of indications and drug dosing. Methods: We examined the prevalence and clinical correlates of clozapine treat...

Objective: Mood stabilizers are psychotropic drugs mainly used to treat bipolar disorder in the acute phase or for maintenance therapy to prevent relapse. In clinical practice, mood stabilizers are commonly prescribed for conditions other than bipolar disorder. This study investigated the distribution of mood stabilizer prescriptions for different...

Introduction Hikikomori, a form of pathological social withdrawal, has been suggested to have comorbidity with autism spectrum disorder (ASD). This study aimed to clarify how characteristics of ASD are associated with hikikomori. Methods Thirty-nine adult male patients with a diagnosis of ASD attending our outpatient clinic for neurodevelopmental...

Internet addiction (IA) is defined as the condition of being addicted to all sorts of activities on the Internet. Individuals with neurodevelopmental disorders, including autism spectrum disorder (ASD), may be susceptible to IA. Early detection and intervention for probable IA are important to prevent severe IA. In this study, we investigated the c...

Epileptic seizures are distinct but frequent comorbidities in children with autism spectrum disorder (ASD). The hyperexcitability of cortical and subcortical neurons appears to be involved in both phenotypes. However, little information is available concerning which genes are involved and how they regulate the excitability of the thalamocortical ne...

Only 50% of patients with depression respond to the first antidepressant drug administered. Thus, biomarkers for prediction of antidepressant responses are needed, as predicting which patients will not respond to antidepressants can optimize selection of alternative therapies. We aimed to identify biomarkers that could predict antidepressant respon...

Backgrounds Hikikomori, 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...

Introduction: Drug-induced extrapyramidal syndrome (EPS) remains a major problem in clinical psychiatry. This study aimed to examine the factor structure of drug-induced extrapyramidal symptoms observed in patients with schizophrenia and assessed using the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS). Methods: The participants were 1478 p...

Aim: Several studies reported stress-induced microglial phagocytosis, but the biochemical mechanisms by which stress alters microglial synaptic phagocytosis are not fully uncovered. Local or limited apoptosis without cell death was observed at neuronal synapses in previous studies, and proposed as an upstream mechanism for microglial synapse elimi...

The accepted version of the above article was posted prematurely on 28 October 2022. The final version of record will be made fully available at a later date.

A pilot study examined the efficacy of the Gatekeeper Training Program designed for suicide prevention in Yogo teachers. The author explored the program’s effectiveness on Yogo teachers with over 20 and under 20 years of experience. Self-administered questionnaires were administered before and after the program to assess the teachers’ confidence in...

Background We aimed to explore the overall network structure of problematic smartphone use symptoms assessed by smartphone addiction scale-short version (SAS-SV) and to identify which items could play important roles in the network. Methods 487 college and university students filled out the study questionnaire, including SAS-SV. We constructed a r...

Background Despite a confirmed association between Problematic Internet use (PIU) and hikikomori-like social withdrawal, few studies investigated differences between sexes. Hence, the main objective was identifying psychopathological predictors (including hikikomori-like traits) associated with PIU (vs. non-PIU) across both sexes. Methods A total...

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 pr...

Psychotic symptoms are rarely concurrent with the clinical manifestations of depression. Additionally, whether psychotic major depression is a subtype of major depression or a clinical syndrome distinct from non-psychotic major depression remains controversial. Using data from the Research on Asian Psychotropic Prescription Patterns for Antidepress...

Mitochondrial fission factor (MFF) is an adapter that targets dynamin-related protein 1 from the cytosol to the mitochondria for fission. Loss-of-function MFF mutations cause encephalopathy due to defective mitochondrial and peroxisomal fission 2 (EMPF2). To elucidate the molecular mechanisms that were involved, we analyzed the functional effects o...

Given the pandemic of COVID-19, many countries including Japan implemented curfew restrictions. Unlike other countries, there were no legal penalties for such restrictions in Japan. However, many citizens voluntarily imposed curfew restrictions. This review paper introduces the impact of this on mental health based on our recent survey studies of J...

Introduction Hikikomori is a Japanese term etymologically derived from ‘ hiku’ (i.e. ‘ to pull back’) and ‘ komoru’ (i.e. ‘ seclude oneself’), which identifies those subjects who deliberately withdraw themselves by social life, remaining confined into their own home/room. The phenomenon is widely diffused in Japan, even though it is currently sprea...

The augmentation of clozapine with electroconvulsive therapy (ECT) has been an optimal treatment option for patients with treatment- or clozapine-resistant schizophrenia. Using data from the Research on Asian Psychotropic Prescription Patterns for Antipsychotics survey, which was the largest international psychiatry research collaboration in Asia,...

Repetitive transcranial magnetic stimulation (rTMS) improves depressive symptoms in treatment-resistant depression (TRD). This study aimed to analyze changes in cerebrospinal fluid (CSF) metabolites in patients with TRD after rTMS. Five patients with TRD were enrolled in a high frequency (10-Hz) rTMS study. The concentration of 72 CSF metabolites w...

Down syndrome (DS) is one of the common genetic disorders caused by the trisomy of human chromosome 21 (HSA21). Mitochondrial dysfunction and redox imbalance play important roles in DS pathology, and altered dopaminergic regulation has been demonstrated in the brain of individuals with DS. However, the pathological association of these elements is...

Background: Because use and dosing of mood stabilizers (MSs) to treat bipolar disorder (BD) patients in Asia are not well documented, we examined prevalence and clinical correlates of treatment of Asian BD patients with relatively high doses of MSs. Methods: We conducted a pharmacoepidemiological survey across 13 Asian countries and territory in...

Microglia play a major role in immune response in the brain. Recent progress in studies for microglia suggests that stress causes morphological alterations in microglia and affects microglial humoral release and phagocytosis. In this review, we present a molecular mechanism by which stress impacts microglia. Then, we describe current findings for t...

Background We aimed to determine the similarities and differences in the roles of genic and regulatory copy number variations (CNVs) in bipolar disorder (BD), schizophrenia (SCZ), and autism spectrum disorder (ASD). Methods Based on high-resolution CNV data from 8708 Japanese samples, we performed the largest known cross-disorder analysis of genic...

Refractory pain disease plagues many people, and relieving chronic pain is a major challenge for all patients. Fibromyalgia, which is classified as intractable pain, is a disease that causes widespread severe pain and is known to be accompanied by various concomitant symptoms such as physical and psychiatric symptoms. On the other hand, fibromyalgi...

Background: The pathophysiology of hikikomori has not been clarified, and biological traits that objectively characterize it remain unexplored. Methods: Drug-free patients with hikikomori conditions (n=42) and healthy controls (n=41) were recruited. Psychological assessments for the severity of hikikomori (HQ-25) and depression (PHQ-9 and HAMD-17)...

Postmortem brain analysis and PET imaging analysis are two major methods to estimate microglial activation in human subjects, and these studies have suggested activation of human microglia in the brain of patients with various neuropsychiatric disorders. However, by using the above methods, only limited aspects of microglial activation can be measu...

Objective: Pharmacotherapy including mood stabilizers and antipsychotics are frequently used in bipolar disorder (BD); however, the lack of consensus regarding the definition of polypharmacy hinders conducting comparative studies across different settings and countries. Research on Asian Prescription Pattern (REAP) is the largest and the longest l...

Background Modern-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. Aim To determine possible associations between psychological traits related to MTD and the chronic pain of patients at psychiatric clinics. Method Two hundred and twe...

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 fema...

The symptom heterogeneity of schizophrenia is consistent with Wittgenstein’s analogy of a language game. From the perspective of precision medicine, this study aimed to estimate the symptom presentation and identify the psychonectome in Asian patients, using data obtained from the Research on Asian Psychotropic Prescription Patterns for Antipsychot...

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 e...

Cryopreservation of whole blood is useful for DNA collection, and clinical and basic research. Blood samples in ethylenediaminetetraacetic acid disodium salt (EDTA) tubes stored at − 80 °C are suitable for DNA extraction, but not for high-quality RNA extraction. Herein, a new methodology for high-quality RNA extraction from human blood samples is d...

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 pol...

Hikikomori, a severe form of social withdrawal, is a condition characterized by the avoidance of social participation and staying at home for more than 6 months. Hikikomori was initially reported in Japan in the 1990s and is now observed worldwide. Here, we introduce specialized psychodynamic group psychotherapy for persons with hikikomori, and ill...

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 si...

Transient receptor potential vanilloid member 4 (TRPV4) is a Ca²⁺ permeable nonselective cation channel, and mutations in the TRPV4 gene cause congenital skeletal dysplasias and peripheral neuropathies. Although TRPV4 is widely expressed in the brain, few studies have assessed the pathogenesis of TRPV4 mutations in the brain. We aimed to elucidate...

Stress is a trigger for depression and PTSD, with current studies suggesting the involvement of microglial hyperactivation and dysfunction in the pathophysiology of these diseases. In this review, we introduced microglial functional changes in animal models, which exhibit fear memory dysregulation that is characteristic of PTSD, and human microglia...

Hikikomori is a form of pathological social withdrawal or social isolation whose essential feature is physical isolation in one's home. The 2010 Japanese guidelines define that a person must meet the following criteria to be diagnosed with hikiikomori: a) marked social isolation in one's home; b) duration of continuous social isolation of at least...

Hikikomori (a severe form of social withdrawal) is a serious mental health issue. A family approach is the initial step to support hikikomori; thus effective family intervention programs are warranted. We recently developed a 5-day family intervention program (120 min weekly) based on Mental Health First Aid (MHFA) and Community Reinforcement and F...

Suicide is a leading cause of death among Japanese college and university students. Our previous study showed that the gatekeeper training (GKT) program significantly improved competence and confidence in the management of suicidal students in university administrative staff. However, we could not determine which component of the program was effect...

Neurofibromatosis type 1 is an autosomal dominant genetic disorder caused by mutation in the neurofibromin 1 ( NF1 ) gene. Its hallmarks are cutaneous findings including neurofibromas, benign peripheral nerve sheath tumors. We analyzed the collagen and matrix metalloproteinase 1 (MMP1) expression in Neurofibromatosis 1 cutaneous neurofibroma and fo...

Targeting the unique glioma immune microenvironment is a promising approach in developing breakthrough immunotherapy treatments. However, recent advances in immunotherapy, including the development of immune checkpoint inhibitors, have not improved the outcomes of patients with glioma. A way of monitoring biological activity of immune cells in neur...

Background Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive brain stimulation technique that is considered a valuable and promising technique for improving depressive symptoms in treatment-resistant depression (TRD). However, the exact mechanism by which rTMS ameliorates depressive symptoms remains to be clarified. Objective Th...

Microglia have been highlighted to understand the underlying pathophysiology of various neuropsychiatric disorders. Postmortem brain analysis and PET imaging analysis are two major methods to estimate microglial activation in humans, however only a limited aspect of microglial activation can be measured by these methods. Dynamic analysis using fres...

Technological innovations in the field of cell differentiation from iPS cells has made it possible to induce dopamine neurons, inhibitory GABA neurons, and even excitatory glutamate neurons, as well as peripheral neurons such as sensory and motor neurons. Thus, we have been able to analyze the mechanisms of disease in specific cells that are target...

Microglia are intrinsic immune cells that release factors including pro- and anti-inflammatory cytokines, nitric oxide (NO) and neurotrophins following activation in the brain. Elevation of intracellular Ca2+ concentration ([Ca2+ ]i) is important for microglial functions, such as the release of cytokines or NO from activated microglia. Brain-derive...

We herein report two cases with carbon monoxide- (CO-) induced delayed neuropsychiatric sequelae (DNS) successfully treated with hyperbaric oxygen therapy (HBOT) in attempt suicide by charcoal burning. The two patients with CO-induced DNS were successfully treated with a total of more than 100 sessions of HBOT. Frontal assessment battery (FAB) was...

Drug-induced extrapyramidal syndrome (EPS) remains a major problem in clinical psychiatry. This study aimed to examine the factor structure of drug-induced extrapyramidal symptoms observed in patients with schizophrenia and assessed using the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS). The participants were 1,478 patients with a diagnosis...

Purpose of review: Direct face-to-face interview between a psychiatrist and a patient is crucial in psychiatric evaluation, however, such traditional interviews are becoming difficult to conduct because of the infection risk in the COVID-19 era. As telepsychiatry, video interviews using internet are suggested to be useful to evaluate and assist in...

Interpersonal difficulties are often observed in major depressive disorder (MDD), while the underlying psychological and biological mechanisms have not yet been elucidated. In the present case–control study, a PC-based trust game was conducted for 38 drug-free MDD patients and 38 healthy controls (HC). In the trust game, participants invested money...

Background The relationship between depression and personality has long been suggested, however, biomarker investigations for depression have mostly overlooked this connection. Methods We collected personality traits from 100 drug-free patients with major depressive disorders (MDD) and 100 healthy controls based on the Five-Factor Model (FFM) such...

Microglia, immune cells in the brain, play a crucial role in brain inflammation and synaptic plasticity by releasing inflammatory mediators and neurotrophic factors as well as, phagocytosing synaptic elements. Recent studies have shown peripheral inflammation, immune alteration in the brain are associated with post-traumatic stress disorder (PTSD)...

Background: A severe form of pathological social withdrawal, 'hikikomori,' has been acknowledged in Japan, spreading worldwide, and becoming a global health issue. The pathophysiology of hikikomori has not been clarified, and its biological traits remain unexplored. Methods: Drug-free patients with hikikomori (n = 42) and healthy controls (n = 4...

Accumulating evidence suggests that elevated inflammation contributes to the pathophysiology of post-traumatic stress disorder (PTSD) and that anti-inflammatory drugs might be a new treatment strategy for PTSD. It has been reported that beta-hydroxybutyrate (BHB), one of the main ketone bodies produced, can have an anti-inflammatory and antidepress...

INTRODUCTION: As recent advancement of multimodal treatments including immune-check point inhibitors have not led to massive outcome improvement of glioma. Targeting the peculiar immune microenvironment of glioma is a promising approach to innovate a breakthrough treatment, however, there remains to be technical and ethical burdens for monitoring t...

Aim: Neurofibromatosis type 1 (NF1) is a multifaceted disease, and frequently comorbid with neurodevelopmental disorders such as autism spectrum disorder (ASD) and learning disorder. Dysfunction of adenylyl cyclase (AC) is one of the candidate pathways in abnormal development of neuronal cells in the brain of NF1 patients, while its dynamic abnorm...

Since optimal treatment at an early stage leads to remission of symptoms and recovery of function, putative biomarkers leading to early diagnosis and prediction of therapeutic responses are desired. The current study aimed to use a metabolomic approach to extract metabolites involved in both the diagnosis of major depressive disorder (MDD) and the...