Kyushu University Academic Staff Educational and Research Activities Database
List of Papers
Takahiro A. Kato Last modified date:2021.09.10

Associate Professor / Department of Neuropsychiatry, Graduate School of Medical Sciences / Department of Clinical Medicine / Faculty of Medical Sciences


Papers
1. Yamagata H*, Kobayashi A, Tsunedomi R, Seki T, Kobayashi M, Hagiwara K, Chen C, Uchida S, Okada G, Fuchikami M, Kamishikiryo T, Iga J, Numata S, Kinoshita M, Kato TA, Hashimoto R, Nagano H, Okamoto Y, Ueno S, Ohmori T, Nakagawa S, Optimized protocol for the extraction of RNA and DNA from frozen whole blood sample stored in a single EDTA tube, Scientific Reports, 10.1038/s41598-021-96567-2, 11, 1, 17075-17075, 2021.08.
2. Katsuki R, Kubo H, Yamakawa I, Shinfuku N, Sartorius N, Sakamoto S, Kato TA*, Association between self-restraint behavior, stigma and depressive tendency in office workers during the COVID-19 pandemic in Japan, Psychiatry International, 10.3390/psychiatryint2030023, 2, 3, 300-309, 2021.08.
3. Kubo H, Aida N, Kato TA*, Psychodynamic group psychotherapy for hikikomori: the case of a socially withdrawn male with schizoaffective disorder, Journal of Clinical Psychology, doi: 10.1002/jclp.23216, 2021.07.
4. Tsuji G*, Takai-Yumine A, Kato TA, Metalloproteinase 1 downregulation in neurofibromatosis 1: Therapeutic potential of antimalarial hydroxychloroquine and chloroquine, Cell Death and Disease, 10.1038/s41419-021-03802-9, 12, 6, 513-513, 2021.07.
5. Kubo H, Urata H, Sakai M, Nonaka S, Kishimoto J, Saito K, Tateno M, Kobara K, Fujisawa D, Hashimoto N, Suzuki Y, Honda Y, Otsuka K, Kanba S, Kuroki T, Kato TA*, Development of 3-day Intervention Program for Family Members of Hikikomori Sufferers. , Japanese Psychological Research, doi:10.1111/jpr.12368, 2021.06.
6. Tanaka S, Ohgidani M, Hata N, Inamine S, Sagata N, Shirouzu N, Mukae N, Suzuki SO, Hamasaki H, Hatae R, Sangatsuda Y, Fujioka Y, Takigawa K, Funakoshi Y, Iwaki T, Hosoi M, Iihara K, Mizoguchi M and Kato TA*, CD206 Expression in Induced Microglia-Like Cells From Peripheral Blood as a Surrogate Biomarker for the Specific Immune Microenvironment of Neurosurgical Diseases Including Glioma, Frontiers in Immunology, 10.3389/fimmu.2021.670131, 12, 2021.06.
7. Monji A, Tateishi H, Murakawa T, Matsushima J, Kunitake Y, Shiraishi T, Kojima R, Inaba T, Kato TA, Mizoguchi Y, Hyperbaric Oxygen Therapy for Carbon Monoxide-Induced Delayed Neuropsychiatric Sequelae: Case Report of Two Cases and Relevant Literature Review, Case Reports in Psychiatry, 10.1155/2021/6663824, 2021, 1-4, Article ID 6663824, 2021.03.
8. Kato TA, Sartorius N, Shinfuku N, Forced social isolation due to COVID-19 and consequent mental health problems: lessons from hikikomori, Psychiatry and Clinical Neurosciences, 10.1111/pcn.13112, 74, 9, 506-507, 2020.09.
9. Setoyama D, Yoshino A, Takamura M, Okada G, Iwata M, Tsunetomi K, Ohgidani M, Kuwano N, Yoshimoto J, Okamoto Y, Yamawaki S, Kanba S, Kang D, Kato TA, Personality classification enhances blood metabolome analysis and biotyping for major depressive disorders: two-species investigation, Journal of Affective Disorders, 10.1016/j.jad.2020.09.118, 279, 2021, 20-30, 2020.09.
10. Alan R. Teo, Sarah Nelson, Wynn Strange, Hiroaki Kubo, Ryoko Katsuki, Keita Kurahara, Shigenobu Kanba, Takahiro A. Kato, Social withdrawal in major depressive disorder
a case-control study of hikikomori in japan, Journal of Affective Disorders, 10.1016/j.jad.2020.06.011, 274, 1142-1146, 2020.09, Background: Social withdrawal is a feature of a number of psychiatric disorders including major depressive disorder (MDD), yet research examining social withdrawal as a feature of MDD is rare. Methods: This was a retrospective case-control study. Participants (N = 67) were recruited through an outpatient clinic at an academic medical center in Japan. Major depressive disorder (MDD) and social withdrawal were established with the Structured Clinical Interview for DSM-IV Axis I Disorders and a semi-structured psychiatric interview, respectively. Participants also completed self-report measures. Results: We classified 24 participants as cases (MDD with social withdrawal) and 43 participants as controls (MDD without social withdrawal). Cases, on average, were more likely to have lower education level, prior episodes of depression, and higher suicidal ideation at baseline than controls. In unadjusted regression models, cases had significantly less social connection, less reward dependence, less self-directedness, and higher scores on scales of modern-type depression and hikikomori. In adjusted regression models, associations between social withdrawal and hikikomori (p<0.01) and reward dependence (p = 0.03) remained significant. Limitations: The sample was limited in size and drawn from a single site. Conclusions: In patients with MDD, social withdrawal may have subtle associations with clinical symptoms, social connection, and personality traits. Developing a better understanding of social withdrawal's phenotype in depression requires more in-depth examination..
11. Seon-Cheol Park, Adarsh Tripathi, Ajit Avasthi, Sandeep Grover, Andi J. Tanra, Takahiro A. Kato, Toshiya Inada, Kok Yoon Chee, Mian-Yoon Chong, Shu-Yu Yang, Sih-Ku Lin, Kang Sim, Yu-Tao Xiang, Afzal Javed, Norman Sartorius, Naotaka Shinfuku, Yong Chon Park, Relationship Between Body Mass Index and Extrapyramidal Symptoms in Asian Patients with Schizophrenia: The Research on Asian Psychotropic Prescription Patterns for Antipsychotics (REAP-AP), Psychiatria Danubina, 10.24869/psyd.2020.176, 32, 2, 176-186, 2020.08.
12. Lim W K,Chew Q H, He YL, Si TM, Chiu FK H, Xiang Y T, Kato TA, Kanba S, Shinfuku N, Lee M S, Park SC, Park YC, Chong MY, Lin SK, u Yang SY, Tripathi A, Avasthi A, Grover S, Kallivayalil RA, Udomratn P, Chee KY, Tanra AJ, Rabbani MG, Javed A, Kathiarachchi S, Waas D, Myint WA, Sartorius N, Tran VC, Nguyen KV, Tan CH, Baldessarini RJ, Sim K*, Coprescription of mood stabilizers in schizophrenia, dosing, and clinical correlates: An international study, Human Psychopharmacology Clinical and Experimental, 10.1002/hup.2752, e2752-e2752, 2020.08.
13. Hiroshi Tateishi, Yoshito Mizoguchi, Atsushi Kawaguchi, Yoshiomi Imamura, Jun Matsushima, Hiroko Kunitake, Toru Murakawa, Yoshinori Haraguchi, Yutaka Kunitake, Toshihiko Maekawa, Takahiro A. Kato, Toyoko Asami, Akira Monji, Changes in interleukin-1 beta induced by rTMS are significantly correlated with partial improvement of cognitive dysfunction in treatment-resistant depression
a pilot study, Psychiatry research, 10.1016/j.psychres.2020.112995, 289, 2020.07, The impairment experienced by many individuals with depression is closely related to the cognitive symptoms of the disorder. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive brain stimulation method that provides a promising technique for improving cognitive symptoms in treatment-resistant depression (TRD). It has recently been demonstrated that TRD is associated with increased inflammatory process. In the present study, we investigated whether a relationship exists between changes in cognitive function and those in inflammatory cytokines before and after rTMS treatment. Eleven patients with TRD were enrolled in a high-frequency (10 Hz) rTMS study. Cognitive function, depressive symptoms and serum concentration of inflammatory cytokines (interleukin (IL)-1β, IL-6 and tumor necrosis factor-α) were measured at baseline and at the endpoint of rTMS treatment. rTMS treatment significantly improved depressive symptom scores and some subscales of cognitive dysfunction. The present study has demonstrated that partial changes in cognitive function and changes in IL-1β were significantly correlated. The partial improvement of cognitive dysfunction by rTMS in the present study might be attributable to the reduction of peripheral IL-1β levels. The present results should be replicated for verification in future studies..
14. Seon Cheol Park, Eun Young Jang, Yu Tao Xiang, Shigenobu Kanba, Takahiro A. Kato, Mian Yoon Chong, Shih Ku Lin, Shu Yu Yang, Ajit Avasthi, Sandeep Grover, Roy A. Kallivayalil, Pichet Udomratn, Kok Yoon Chee, Andi J. Tanra, Chay Hoon Tan, Kang Sim, Norman Sartorius, Yong Chon Park, Naotaka Shinfuku, Network analysis of the depressive symptom profiles in Asian patients with depressive disorders
Findings from the Research on Asian Psychotropic Prescription Patterns for Antidepressants (REAP-AD), Psychiatry and clinical neurosciences, 10.1111/pcn.12989, 74, 6, 344-353, 2020.06, Aim: We aimed to estimate the network structures of depressive symptoms using network analysis and evaluated the geographic regional differences in theses network structures among Asian patients with depressive disorders. Methods: Using data from the Research on Asian Psychotropic Prescription Patterns for Antidepressants (REAP-AD), the network of the ICD-10 diagnostic criteria for depressive episode was estimated from 1174 Asian patients with depressive disorders. The node strength centrality of all ICD-10 diagnostic criteria for a depressive episode was estimated using a community-detection algorithm. In addition, networks of depressive symptoms were estimated separately among East Asian patients and South or Southeast Asian patients. Moreover, networks were estimated separately among Asian patients from high-income countries and those from middle-income countries. Results: Persistent sadness, fatigue, and loss of interest were the most centrally situated within the network of depressive symptoms in Asian patients with depressive disorders overall. A community-detection algorithm estimated that when excluding psychomotor disturbance as an outlier, the other nine symptoms formed the largest clinically meaningful cluster. Geographic and economic variations in networks of depressive symptoms were evaluated. Conclusion: Our findings demonstrated that the typical symptoms of the ICD-10 diagnostic criteria for depressive episode are the most centrally situated within the network of depressive symptoms. Furthermore, our findings suggested that cultural influences related to geographic and economic distributions of participants could influence the estimated depressive symptom network in Asian patients with depressive disorders..
15. Seon Cheol Park, Gyung Mee Kim, Takahiro A. Kato, Mian Yoon Chong, Shih Ku Lin, Shu Yu Yang, Ajit Avasthi, Sandeep Grover, Roy Abraham Kallivayalil, Yu Tao Xiang, Kok Yoon Chee, Andi Jayalangkara Tanra, Chay Hoon Tan, Kang Sim, Norman Sartorius, Naotaka Shinfuku, Yong Chon Park, Toshiya Inada, Dyskinesia is most centrally situated in an estimated network of extrapyramidal syndrome in Asian patients with schizophrenia
findings from research on Asian psychotropic prescription patterns for antipsychotics, Nordic Journal of Psychiatry, 10.1080/08039488.2020.1777462, 2020.06, Background: Network analysis provides a new viewpoint that explicates intertwined and interrelated symptoms into dynamic causal architectures of symptom clusters. This is a process called ‘symptomics’ and is concurrently applied to various areas of symptomatology. Aims: Using the data from Research on Asian Psychotropic Prescription Patterns for Antipsychotics (REAP-AP), we aimed to estimate a network model of extrapyramidal syndrome in patients with schizophrenia. Methods: Using data from REAP-AP, extrapyramidal symptoms of 1046 Asian patients with schizophrenia were evaluated using the nine items of the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS). The estimated network of the ordered-categorical DIEPSS items consisted of nodes (symptoms) and edges (interconnections). A community detection algorithm was also used to identify distinctive symptom clusters, and correlation stability coefficients were used to evaluate the centrality stability. Results: An interpretable level of node strength centrality was ensured with a correlation coefficient. An estimated network of extrapyramidal syndrome showed that 26 (72.2%) of all possible 35 edges were estimated to be greater than zero. Dyskinesia was most centrally situated within the estimated network. In addition, earlier antipsychotic-induced extrapyramidal symptoms were divided into three distinctive clusters–extrapyramidal syndrome without parkinsonism, postural instability and gait difficulty-dominant parkinsonism, and tremor-dominant parkinsonism. Conclusions: Our findings showed that dyskinesia is the most central domain in an estimated network structure of extrapyramidal syndrome in Asian patients with schizophrenia. These findings are consistent with the speculation that acute dystonia, akathisia, and parkinsonism could be the risk factors of tardive dyskinesia..
16. Sachie Kaneko, Takahiro A. Kato, Manabu Makinodan, Takashi Komori, Rio Ishida, Naoko Kishimoto, Masato Takahashi, Yuka Yasuda, Ryota Hashimoto, Hidemi Iwasaka, Ayumi Tanaka, Yukiko Uchida, Shigenobu Kanba, Toshifumi Kishimoto, The Self-Construal Scale
A Potential Tool for Predicting Subjective Well-Being of Individuals With Autism Spectrum Disorder, Autism Research, 10.1002/aur.2242, 13, 6, 947-958, 2020.06, Despite accumulating evidence that culture shapes the symptoms of autism spectrum disorder (ASD), no studies have yet applied the Self-Construal Scale to individuals with ASD. We compared the self-construals (measured using the Self-Construal Scale) of 31 high-functioning Japanese individuals with ASD with those of 60 typically developing (TD) individuals. We also examined how the self-construals of individuals with ASD related to their intelligence quotient, adverse childhood experiences, attention deficit hyperactivity disorder, ASD symptoms during adulthood and preschool years, and subjective well-being. Individuals with ASD were more likely to display independent self-construals than were TD individuals; unexpectedly, however, a substantial proportion of individuals with ASD (43.8%) displayed relatively interdependent self-construals. Among individuals with ASD, self-construals were significantly associated with ASD symptoms during preschool years, and with satisfaction of the need for autonomy and frustration of the need for relatedness. Evaluating self-construals can help predict the subjective well-being of high-functioning individuals with ASD. Moreover, the Self-Construal Scale may be useful for understanding the heterogeneous phenotypes of ASD, based on its association with autistic symptoms during preschool years, suggesting that the scale is a potential tool to develop efficient interventions for high-functioning individuals with ASD. Autism Res 2020, 13: 947-958..
17. Takahiro A. Kato, Naotaka Shinfuku, Masaru Tateno, Internet society, internet addiction, and pathological social withdrawal
the chicken and egg dilemma for internet addiction and hikikomori, Current opinion in psychiatry, 10.1097/YCO.0000000000000601, 33, 3, 264-270, 2020.05, PURPOSE OF REVIEW: Internet society has made our daily life more convenient, while its negative consequences especially internet, smartphone, and gaming addiction are emerging. At the same time, the phenomenon of pathological social withdrawal called 'hikikomori' has been increasingly highlighted as a problematic behavior in Japan. Now hikikomori is becoming a global mental health issue. The interaction between internet society, internet addiction, and hikikomori has not been well clarified. RECENT FINDINGS: A case vignette survey among psychiatrists suggested that hikikomori cases could be comorbid with internet addiction. In reality, hikikomori cases with internet addiction have been reported internationally. A recent survey among college/university students in Japan has indicated positive interactions between internet addiction, smartphone addiction, gaming internet disorder, and hikikomori-tendencies. SUMMARY: The cause of hikikomori has not been well understood, and the emergence of internet may be one of the important contributing factors for the occurrence of hikikomori. Whether pathological social withdrawal creates internet addiction, or internet overuse creates hikikomori remains unclear. Both possibilities exist, and we herein propose the conceptual model of these hypothetical interactions. Clarifying the mechanisms of both conditions will help to solve these crucial issues for contemporary urban societies..
18. Chao Tian Tang, Ee Cheong Chua, Qian Hui Chew, Yan‐Ling He, Tian‐Mei Si, Helen F.‐K. Chiu, Yu‐Tao Xiang,Takahiro A. Kato ,Shigenobu Kanba, Naotaka Shinfuku, Min‐Soo Lee, Seon‐Cheol Park, Yong‐Chon Park, Mian‐Yoon Chong, Shih‐Ku Lin, Shu‐Yu Yang, Adarsh Tripathi, Ajit Avasthi, Sandeep Grover, Roy A. Kallivayalil, Pichet Udomratn, Kok Yoon Chee, Andi J. Tanra, Md Golam Rabbani, Afzal Javed, Samudra Kathiarachchi, Dulshika Waas, Wing Aung Myint, Norman Sartorius, Van Cuong Tran, Kim Viet Nguyen, Chay‐Hoon Tan, Ross J. Baldessarini, Kang Sim, Patterns of Long Acting Injectable Antipsychotic Use and Associated Clinical Factors in Schizophrenia Amongst 15 Asian Countries and Region, Asia-Pacific Psychiatry, 10.1111/appy.12393, e12393, 2020.05, [URL].
19. Tan MPJ*, Lee WE, Kato TA, International experience of Hikikomori (prolonged social withdrawal), and its relevance to psychiatric research, BJPsych International, 10.1192/bji.2020.20, 1-3, 2020.05.
20. Takahiro A. Kato, Shigenobu Kanba, Alan R. Teo, Defining pathological social withdrawal proposed diagnostic criteria for hikikomori, World Psychiatry, 10.1002/wps.20705, 19, 1, 116-117, 2020.02.
21. Kanako Nozaki, Hikaru Ito, Masahiro Ohgidani, Yosuke Yamawaki, Ezgi Hatice Sahin, Takashi Kitajima, Seishi Katsumata, Shigeto Yamawaki, Takahiro A. Kato, Hidenori Aizawa, Antidepressant effect of the translocator protein antagonist ONO-2952 on mouse behaviors under chronic social defeat stress, Neuropharmacology, 10.1016/j.neuropharm.2019.107835, 162, 2020.01, In preclinical models, it has been reported that social defeat stress activates microglial cells in the CNS. Translocator protein 18 kDa (TSPO) is a mitochondrial protein expressed on microglia in the CNS that has been proposed to be a useful biomarker for brain injury and inflammation. We hypothesized that a TSPO antagonist, ONO-2952, would inhibit the neuroinflammation induced by microglial hyperactivation and associated depressive-like behaviors. An in vitro analysis showed that ONO-2952 suppressed the release of pro-inflammatory cytokines and mitochondrial reactive oxygen species in cultured microglia stimulated by lipopolysaccharide. In mice submitted to chronic social defeat stress, microglia predominantly expressed TSPO in limbic areas implicated in depressive-like behaviors, including the amygdala, ventral hippocampus and nucleus accumbens, in which an increase in the production of pro-inflammatory cytokines in vivo were associated. Treating animals with ONO-2952 during chronic social defeat stress ameliorated impairments in social avoidance and anxiety-like behaviors and suppressed pro-inflammatory cytokine production, suggesting that ONO-2952 exerted an anti-stress effect in this animal model of depression. Thus, targeting TSPO as a candidate for the development of antidepressants that reduce susceptibility to chronic stress could pave the way toward therapeutic interventions for relapse prophylaxis in depression..
22. Hiroaki Kubo, Hiromi Urata, Motohiro Sakai, Shunsuke Nonaka, Kazuhiko Saito, Masaru Tateno, Keiji Kobara, Naoki Hashimoto, Daisuke Fujisawa, Yuriko Suzuki, Kotaro Otsuka, Hiroho Kamimae, Yuya Muto, Takashi Usami, Yoko Honda, Junji Kishimoto, Toshihide Kuroki, Shigenobu Kanba, Takahiro A. Kato, Development of 5-day hikikomori intervention program for family members
A single-arm pilot trial, Heliyon, 10.1016/j.heliyon.2019.e03011, 6, 1, 2020.01, Clinical psychology; Depression; Mental health; Psychiatry; Suicide; Pathological social withdrawal (hikikomori); Depression; Social anxiety; Mental health first aid (MHFA); Community reinforcement and family training (CRAFT); Family support.
23. Hidetoshi Tozaki-Saitoh, Izumi Sasaki, Tomohiro Yamashita, Masako Hosoi, Takahiro A. Kato, Makoto Tsuda, Involvement of exchange protein directly activated by cAMP and tumor progression locus 2 in IL-1β production in microglial cells following activation of β-adrenergic receptors, Journal of Pharmacological Sciences, 10.1016/j.jphs.2020.03.004, 2020.01, Endogenous noradrenaline (NA) has multiple bioactive functions and, in the central nervous system (CNS), has been implicated in modulating neuroinflammation via β-adrenergic receptors (β-ARs). Microglia, resident macrophages in the CNS, have a central role in the brain immune system and have been reported to be activated by NA. However, intracellular signaling mechanisms of the AR-mediated proinflammatory responses of microglia are not fully understood. Using a rapid and stable in vitro reporter assay system to evaluate IL-1β production in microglial BV2 cells, we found that NA and the β-AR agonist isoproterenol upregulated the IL-1β reporter activity. This effect was suppressed by β-AR antagonists. We further examined the involvement of EPAC (exchange protein directly activated by cAMP) and TPL2 (tumor progression locus 2, MAP3K8) and found that inhibitors for EPAC and TPL2 reduced AR agonist-induced IL-1β reporter activity. These inhibitors also suppressed NA-induced endogenous Il1b mRNA expression and IL-1β protein production. Our results suggest that EPAC and TPL2 are involved in β-AR-mediated IL-1β production in microglial cells, and extend our understanding of its intracellular signaling mechanism..
24. Hiroshi Tateishi, Masashi Nishihara, Atsushi Kawaguchi, Jun Matsushima, Toru Murakawa, Yoshinori Haraguchi, Yutaka Kunitake, Toshihiko Maekawa, Takahiro A. Kato, Toyoko Asami, Yoshito Mizoguchi, Akira Monji, Improvement of frontal lobe dysfunction and white matter integrity by rTMS in treatment-resistant depression, Neuropsychiatric Disease and Treatment, 10.2147/NDT.S228501, 15, 3079-3087, 2019.11, Aim: The impairment experienced by many individuals with depression is closely related to the cognitive symptoms of the disorder. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive brain stimulation method providing a promising technique for improving cognitive symptoms in treatment-resistant depression (TRD). In the present study, we investigated whether a relationship exists between improvements in frontal lobe dysfunction induced by rTMS and improvement of white matter integrity revealed by diffusion tensor imaging (DTI) in TRD patients receiving rTMS treatment. Methods: A total of 12 patients with TRD were enrolled in a high-frequency (10 Hz) rTMS study (August 2013-January 2019). Frontal lobe function and depressive symptoms were assessed at baseline and at the endpoint of rTMS treatment. Fractional anisotropy (FA), as a measure of white matter integrity obtained from DTI, was investigated using a region-ofinterest (ROI) approach. Results: rTMS treatment significantly improved depressive symptom scores and some subscales of frontal lobe dysfunction. Category scores in the Word Fluency Test and scores on part 3 of the Color Stroop Test were improved independently of the improvement of depressive symptoms. In the ROI analysis, none of the FA increases in any region were correlated with improvement of any frontal lobe function (n = 12). Conclusion: Although rTMS resulted in partial improvement of frontal lobe dysfunction as well as white matter integrity, we found no correlation between improved frontal lobe dysfunction and improved white matter integrity in TRD patients..
25. Seon Cheol Park, Eun Young Jang, Kiwon Kim, Hoseon Lee, Joonho Choi, Amitava Dan, Arshad Hussain, Andi Jayalangkara Tanra, Takahiro A. Kato, Kok Yoon Chee, Sih Ku Lin, Chay Hoon Tan, Afzal Javed, Norman Sartorius, Naotaka Shinfuku, Yong Chon Park, Establishing the cut-off scores for the severity ranges of schizophrenia on the BPRS-6 scale
findings from the REAP-AP, Psychiatry and Clinical Psychopharmacology, 10.1080/24750573.2019.1695994, 29, 4, 895-898, 2019.10, Objective: Using data from the Research on Asian Psychotropic Prescription Patterns for Antipsychotics (REAP-AP), our study aimed to establish the remission and severity ranges (mild, moderate, and severe) of schizophrenia on the Brief Psychiatric Rating Scale-6 (BPRS-6). Methods: A total of 1,438 patients with schizophrenia from India, Indonesia, Japan, Malaysia, and Taiwan were enrolled in the study. Using the receiver operating characteristic (ROC) curve analyses, the optimal cut-off scores for the remission and severity ranges on the BPRS-6 were established. Results: The scalability of the BPRS-6 was considered to have an acceptable “unidimensionality” (coefficient of scalability = 0.43). The cut-off scores for the remission of schizophrenia and mild, moderate, and severe schizophrenia can be optimally defined as the BPRS-6 total score of <5, 5–9, 10–19 and >20, respectively. Conclusion: The BPRS-6 can be a promising, brief, and unidimensional rating scale to supplement the measurement-based care of schizophrenia..
26. Takaya Ishii, Mitsuru Ishikawa, Koki Fujimori, Takuji Maeda, Itaru Kushima, Yuko Arioka, Daisuke Mori, Yuhki Nakatake, Bun Yamagata, Shintaro Nio, Takahiro A. Kato, Nan Yang, Marius Wernig, Shigenobu Kanba, Masaru Mimura, Norio Ozaki, Hideyuki Okano, In vitro modeling of the bipolar disorder and schizophrenia using patient-derived induced pluripotent stem cells with copy number variations of PCDH15 and RELN, eNeuro, 10.1523/ENEURO.0403-18.2019, 6, 5, 2019.10, (Figure Presented) Bipolar disorder (BP) and schizophrenia (SCZ) are major psychiatric disorders, but the molecular mechanisms underlying the complicated pathologies of these disorders remain unclear. It is difficult to establish adequate in vitro models for pathological analysis because of the heterogeneity of these disorders. In the present study, to recapitulate the pathologies of these disorders in vitro, we established in vitro models by differentiating mature neurons from human induced pluripotent stem cells (hiPSCs) derived from BP and SCZ patient with contributive copy number variations, as follows: two BP patients with PCDH15 deletion and one SCZ patient with RELN deletion. Glutamatergic neurons and GABAergic neurons were induced from hiPSCs under optimized conditions. Both types of induced neurons from both hiPSCs exhibited similar phenotypes of MAP2 (microtubule-associated protein 2)-positive dendrite shortening and decreasing synapse numbers. Additionally, we analyzed isogenic PCDH15-or RELN-deleted cells. The dendrite and synapse phenotypes of isogenic neurons were partially similar to those of patient-derived neurons. These results suggest that the observed phenotypes are general phenotypes of psychiatric disorders, and our in vitro models using hiPSC-based technology may be suitable for analysis of the pathologies of psychiatric disorders..
27. Andrea Pozza, Anna Coluccia, Takahiro Kato, Marco Gaetani, Fabio Ferretti, The Hikikomori' syndrome
Worldwide prevalence and co-occurring major psychiatric disorders: A systematic review and meta-analysis protocol, BMJ open, 10.1136/bmjopen-2018-025213, 9, 9, 2019.09, Introduction The Hikikomori' syndrome (HS) consists of prolonged and severe social withdrawal. It has been studied first in Japan and recently has increasingly drawn the attention of researchers and clinicians all over the world. It is unclear whether it exists in other cultural contexts than Asia. The existing systematic reviews did not provide a quantitative synthesis on its prevalence. In addition, a summary of the co-occurring rates of psychiatric disorders is lacking. To provide a more comprehensive understanding of the clinical picture, it seems important to investigate which psychiatric disorders listed in the classification systems are most frequently associated with this psychological condition affecting young people. This paper describes a systematic review and meta-analysis protocol summarising worldwide prevalence of the HS in general population and clinical samples with psychiatric disorders. The review will also assess the co-occurrence between HS and each psychiatric disorder defined by any version of the Diagnostic and Statistical Manual of Mental Disorders (DSM) or International Classification of Diseases (ICD) in any clinical samples with psychiatric disorders. Methods and analysis A systematic review will be conducted according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Studies will be included if they use youth aged 12-35 years, recruited from general population or population with psychiatric disorders, if they use international criteria to diagnose HS. No restriction about design or language will be applied. The search will be conducted during the first week of November 2019 by two independent reviewers through the databases Scopus, PubMed, PsycINFO, Web of Science, by examining study references, by looking for conference proceedings/dissertations/theses, by contacting study corresponding authors. Random-effect meta-analysis will be performed by computing effect sizes as logit event rates. Study quality will be assessed through the Newcastle-Ottawa Scale. Ethics and dissemination The current review does not require ethics approval. The results will be disseminated through conference presentations and publications in peer-reviewed journals. PROSPERO registration number CRD 42018098747..
28. Takahiro Kato, Ryoko Katsuki, Hiroaki Kubo, Norihiro Shimokawa, Mina Sato-Kasai, Kohei Hayakawa, Nobuki Kuwano, Wakako Umene-Nakano, Masaru Tateno, Daiki Setoyama, Dongchon Kang, Motoki Watabe, Shinji Sakamoto, Alan R. Teo, Shigenobu Kanba, Development and validation of the 22-item Tarumi's Modern-Type Depression Trait Scale
Avoidance of Social Roles, Complaint, and Low Self-Esteem (TACS-22), Psychiatry and Clinical Neurosciences, 10.1111/pcn.12842, 73, 8, 448-457, 2019.08, Aim: Understanding premorbid personality is important, especially when considering treatment selection. Historically, the premorbid personality of patients with major depression in Japan was described as Shuchaku-kishitsu [similar to Typus melancholicus], as proposed by Shimoda in the 1930s. Since around 2000, there have been increased reports in Japan of young adults with depression who have had premorbid personality differing from the traditional type. In 2005, Tarumi termed this novel condition ‘dysthymic-type depression,’ and more recently the condition has been called Shin-gata/Gendai-gata Utsu-byo [modern-type depression (MTD)]. We recently developed a semi-structured diagnostic interview to evaluate MTD. Development of a tool that enables understanding of premorbid personality in a short time, especially at the early stage of treatment, is desirable. The object of this study was to develop a self-report scale to evaluate the traits of MTD, and to assess the scale's psychometric properties, diagnostic accuracy, and biological validity. Methods: A sample of 340 participants from clinical and community settings completed measures. Psychometric properties were assessed with factor analysis. Diagnostic accuracy of the MTD traits was compared against a semi-structured interview. Results: The questionnaire contained 22 items across three subscales, thus we termed it the 22-item Tarumi's Modern-Type Depression Trait Scale: Avoidance of Social Roles, Complaint, and Low Self-Esteem (TACS-22). Internal consistency, test–retest reliability, and convergent validity were all satisfactory. Among patients with major depression, the area under the curve was 0.757 (sensitivity of 63.1% and specificity of 82.9%) and the score was positively correlated with plasma tryptophan. Conclusion: The TACS-22 possessed adequate psychometric properties and diagnostic accuracy in an initial sample of Japanese adults. Additional research on its ability to support clinical assessment of MTD is warranted..
29. Seon Cheol Park, Hong Seok Oh, Adarsh Tripathi, Roy Abraham Kallivayalil, Ajit Avasthi, Sandeep Grover, Andi Jayalangkara Tanra, Shigenobu Kanba, Takahiro A. Kato, Toshiya Inada, Kok Yoon Chee, Mian Yoon Chong, Shih Ku Lin, Kang Sim, Yu Tao Xiang, Chay Hoon Tan, Afzal Javed, Norman Sartorius, Naotaka Shinfuku, Yong Chon Park, Cannabis use correlates with aggressive behavior and long-acting injectable antipsychotic treatment in Asian patients with schizophrenia, Nordic Journal of Psychiatry, 10.1080/08039488.2019.1632381, 73, 6, 323-330, 2019.08, Background: Although cannabis use has been linked with schizophrenia in a dose–response pattern, to our knowledge, the relationship between cannabis and schizophrenia has rarely been reported in Asian population. Aim: We compared the clinical characteristics and psychotropic prescription patterns between cannabis users and non-users among Asian patients with schizophrenia. Moreover, we aimed to identify the independent correlates of cannabis use in these subjects. Methods: We performed the analysis of the data from the Research on Asian Psychotropic Prescription Patterns for Antipsychotics (REAP-AP), a collaborative consortium survey used to collate the prescription patterns for antipsychotic and other psychotropic medications in patients with schizophrenia in Asia. We included 132 schizophrenia patients in the group of lifetime cannabis use and 1756 in the group that had never used cannabis. A binary logistic model was fitted to detect the clinical correlates of lifetime cannabis use. Results: Adjusting for the effects of age, sex, geographical region, income group, duration of untreated psychosis, and Charlson comordity index level, a binary logistic regression model revealed that lifetime cannabis use was independently associated with aggressive behavior [adjusted odds ratio (aOR) = 1.582, 95% confidence interval (CI) = 1.006–2.490, p =.047] and with long-acting injectable antipsychotic treatment (aOR = 1.796, 95% CI = 1.444–2.820, p =.001). Conclusion: Our findings indicate a close link between lifetime cannabis use and aggressive behavior. The use of long-acting, injectable antipsychotics preferentially treats the aggressive behavior cannabis users among patients with schizophrenia in Asia, especially, the South or Southeast Asia..
30. Eisuke Hayakawa, Masahiro Ohgidani, Yoshinori Fujimura, Shigenobu Kanba, Daisuke Miura, Takahiro A. Kato, Cuprizone-treated mice, a possible model of schizophrenia, highlighting the simultaneous abnormalities of GABA, serine and glycine in hippocampus, Schizophrenia research, 10.1016/j.schres.2019.06.010, 210, 326-328, 2019.08.
31. Masaru Tateno, Dai Jin Kim, Alan R. Teo, Norbert Skokauskas, Anthony P.S. Guerrero, Takahiro Kato, Smartphone addiction in Japanese college students
Usefulness of the japanese version of the smartphone addiction scale as a screening tool for a new form of internet addiction, Psychiatry Investigation, 10.30773/pi.2018.12.25.2, 16, 2, 115-120, 2019.02, ObjectiveaaSmartphone use is pervasive among youth in Japan, as with many other countries, and is associated with spending time online and on social media anywhere at any time. This study aimed to test a Japanese version of the Smartphone Addiction Scale-Short Version (SAS-SV) among Japanese college students. MethodsaaThe subjects of this study were 602 college students in Japan. The study questionnaire consisted of questions about demographics (age, gender etc.), possession of a smartphone, internet use [length of internet use on weekdays and weekend, favorite social networking service (SNS) etc.], Young’s Internet Addiction Test (IAT), and the Smartphone Addiction Scale-Short Version (SAS-SV) translated into Japanese. ResultsaaThere was a total of 573 respondents (180 male, 393 female) who completed the questionnaire (mean 19.3±1.3 years). LINE was the most popular social media platform (52.0%) followed by Twitter (36.3%). The overall Internet Addiction Test (IAT) score was 45.3±13.2, with 4.5% classified as having severe addiction (IAT ≥70). The mean SAS-SV scores were 24.4±10.0 for males and 26.8±9.9 for females. Based on proposed cutoff scores, 22.8% of males and 28.0% of females screened positive for smartphone addiction. The total scores of the SAS-SV and the IAT was correlated significantly. ConclusionaaAs the number of smartphone users becomes higher, problems related to smartphone use also become more serious. Our results suggest that the Japanese version of SAS-SV may assist in early detection of problematic use of smartphones..
32. Hisaomi Suzuki, Masahiro Ohgidani, Nobuki Kuwano, Fabrice Chrétien, Geoffroy Lorin de la Grandmaison, Mitsumoto Onaya, Itaru Tominaga, Daiki Setoyama, Dongchon Kang, Masaru Mimura, Shigenobu Kanba, Takahiro Kato, Suicide and microglia
Recent findings and future perspectives based on human studies, Frontiers in Cellular Neuroscience, 10.3389/fncel.2019.00031, 13, 1-10, 2019.01, Suicide is one of the most disastrous outcomes for psychiatric disorders. Recent advances in biological psychiatry have suggested a positive relationship between some specific brain abnormalities and specific symptoms in psychiatric disorders whose organic bases were previously completely unknown. Microglia, immune cells in the brain, are regarded to play crucial roles in brain inflammation by releasing inflammatory mediators and are suggested to contribute to various psychiatric disorders such as depression and schizophrenia. Recently, activated microglia have been suggested to be one of the possible contributing cells to suicide and suicidal behaviors via various mechanisms especially including the tryptophan-kynurenine pathway. Animal model research focusing on psychiatric disorders has a long history, however, there are only limited animal models that can properly express psychiatric symptoms. In particular, to our knowledge, animal models of human suicidal behaviors have not been established. Suicide is believed to be limited to humans, therefore human subjects should be the targets of research despite various ethical and technical limitations. From this perspective, we introduce human biological studies focusing on suicide and microglia. We first present neuropathological studies using the human postmortem brain of suicide victims. Second, we show recent findings based on positron emission tomography (PET) imaging and peripheral blood biomarker analysis on living subjects with suicidal ideation and/or suicide-related behaviors especially focusing on the tryptophan-kynurenine pathway. Finally, we propose future perspectives and tasks to clarify the role of microglia in suicide using multi-dimensional analytical methods focusing on human subjects with suicidal ideation, suicide-related behaviors and suicide victims..
33. Ryoko Katsuki, Ayako Inoue, Sílvia Indias, Keita Kurahara, Nobuki Kuwano, Fumika Funatsu, Hiroaki Kubo, Shigenobu Kanba, Takahiro Kato, Clarifying deeper psychological characteristics of hikikomori using the rorschach comprehensive system
A pilot case-control study, Frontiers in Psychiatry, 10.3389/fpsyt.2019.00412, 10, JUN, 2019.01, Hikikomori, a form of severe social withdrawal more than 6 months, has increasingly become a crucial issue especially among adolescents. Loneliness, avoidant personality, Japanese culture-related attachment style ("amae"), and difficulty in expressing emotions are suggested to be related to hikikomori. However, deeper psychological aspects have not been well clarified. The Rorschach test is one of the most popular psychological assessment tools to evaluate deeper personality traits. The Rorschach Comprehensive System (CS) has been established as the most reliable scoring method. Until now, no CS research has been conducted focusing on hikikomori. Therefore, we herein conducted a pilot case-control study using CS in clinical cases with and without hikikomori condition. Participants were recruited from the Mood Disorder/Hikikomori Clinic at Kyushu University Hospital. Twenty-Two patients with hikikomori (HK patients) and 18 patients without hikikomori (non-HK patients) participated in the present study. All the 40 participants conducted the self-report Structured Clinical Interview for DSM-IV Axis II Personality Disorders (SCID-II) personality questionnaire and CS. Regarding the SCID-II personality questionnaire, various personality traits including passive aggressive trait were significantly higher in HK patients. Among CS variables, HK patients showed higher scores on FC (Form Color) and SumT (total number of texture-related responses). In addition, frequency of SumT was higher in HK patients. The present results suggest that persons with hikikomori are more likely to express emotions indirectly and expect others to presume their feelings and thoughts. Persons with hikikomori may also have difficulty in becoming independent emotionally from primitive dependence and attachment on significant others. Further investigations with larger samples are warranted for validation..
34. Seon Cheol Park, Eun Young Jang, Gyung Mee Kim, Ajit Avasthi, Sandeep Grover, Andi Jayalangkara Tanra, Takahiro Kato, Kok Yoon Chee, Mian Yoon Chong, Afzal Javed, Chay Hoon Tan, Norman Sartorius, Naotaka Shinfuku, Yong Chon Park, Establishing the cut-off score for aggression on the Brief Psychiatric Rating Scale-Excited Component (BPRS-EC) in schizophrenia patients, Psychiatry and Clinical Psychopharmacology, 10.1080/24750573.2019.1626067, 2019.01, OBJECTIVE: We aimed to present the scalability and cut-off score for the presence of aggression on the Brief Psychiatric Rating Scale-Excited Component (BPRS-EC) in schizophrenia patients. METHODS: From the Research on Asian Psychotropic Prescription Patterns for Antipsychotics, 1,438 Asian patients with schizophrenia were recruited in present study. The Mokken analysis was used to evaluate scalability of the BPRS-EC. The receiver operating characteristic (ROC) curve was used to establish the optimal cut-off score for the presence of aggression on the BPRS-6 in schizophrenia patients. RESULTS: The Mokken model presented that the scalability of the BPRS-EC was considered to have a strong “unidimensionality” (coefficient of scalability = 0.57). The ROC curve showed that, with the cut-off score of 5, the total score on the BPRS-EC distinguished the absence and presence of aggression in schizophrenia patients. CONCLUSION: The BPRS-EC can be used as a supplementary scale for evaluating aggression in patients with schizophrenia..
35. John C. Wong, Michelle J. Wan, Leoniek M. Kroneman, Takahiro Kato, Wing T. Lo, Paul W. Wong, Chan H. Gloria, Hikikomori phenomenon in East Asia
Regional perspectives, challenges and opportunities for social health agencies, Frontiers in Psychiatry, 10.3389/fpsyt.2019.00512, 10, JUN, 2019.01.
36. Masaru Tateno, Alan R. Teo, Wataru Ukai, Junichiro Kanazawa, Ryoko Katsuki, Hiroaki Kubo, Takahiro Kato, Internet addiction, smartphone addiction, and hikikomori trait in Japanese young adult
Social isolation and social network, Frontiers in Psychiatry, 10.3389/fpsyt.2019.00455, 10, JULY, 2019.01, Background: As the number of internet users increases, problems related to internet overuse are becoming more and more serious. Adolescents and youth may be particularly attracted to and preoccupied with various online activities. In this study, we investigated the relationship of internet addiction, smartphone addiction, and the risk of hikikomori, severe social withdrawal, in Japanese young adult. Methods: The subjects were 478 college/university students in Japan. They were requested to complete the study questionnaire, which consisted of questions about demographics, internet use, the Internet Addiction Test (IAT), the Smartphone Addiction Scale (SAS)-Short Version (SV), the 25-item Hikikomori Questionnaire (HQ-25), etc. We investigated the difference and correlation of the results between two groups based on the purpose of internet use or the total score of each self-rating scale, such as screened positive or negative for the risk of internet addiction, smartphone addiction, or hikikomori. Results: There was a trend that males favored gaming in their internet use while females used the internet mainly for social networking via smartphone, and the mean SAS-SV score was higher in females. Two-group comparisons between gamers and social media users, according to the main purpose of internet use, showed that gamers used the internet longer and had significantly higher mean IAT and HQ-25 scores. Regarding hikikomori trait, the subjects at high risk for hikikomori on HQ-25 had longer internet usage time and higher scores on both IAT and SAS-SV. Correlation analyses revealed that HQ-25 and IAT scores had a relatively strong relationship, although HQ-25 and SAS-SV had a moderately weak one. Discussion: Internet technology has changed our daily lives dramatically and altered the way we communicate as well. As social media applications are becoming more popular, users are connected more tightly to the internet and their time spent with others in the real world continues to decrease. Males often isolate themselves from the social community in order to engage in online gaming while females use the internet as to not be excluded from their communications online. Mental health providers should be aware of the seriousness of internet addictions and hikikomori..
37. Shih-Ku Lin, Yen-Feng Lin, Shu-Yu Yang, Yan-Ling He, Takahiro A Kato, Kohei Hayakawa, Yongchon Park, Kang Sim, Helen Fung-Kum Chiu, Yu-tao Xiang, Mian-Yoon Chong, Chay-Hoon Tan, Toshiya Inada, Naotaka Shinfuku, Comparison of the Defined Daily Dose and Chlorpromazine Equivalent Methods in Antipsychotic Drug Utilization in Six Asian Countries, Neuropsychiatry, DOI: 10.4172/Neuropsychiatry.1000527, 8, 6, 1847-1852, 2018.12.
38. Hiroaki Kubo, Hiromi Urata, Ryoko Katsuki, Miyako Hirashima, Shion Ueno, Yuriko Suzuki, Daisuke Fujisawa, Naoki Hashimoto, Keiji Kobara, Tetsuji Cho, Toshiko Mitsui, Shigenobu Kanba, Kotaro Otsuka, Takahiro Kato, Development of MHFA-based 2-h educational program for early intervention in depression among office workers
A single-arm pilot trial, PloS one, 10.1371/journal.pone.0208114, 13, 12, 2018.12, Objective In the workplace depression and suicide are serious mental health problems. A lack of knowledge and mental health skills along with the stigma toward mental health problems often results in delays in seeking professional help. Interventions targeting not only persons with mental health problems but also people around the individual are warranted in order to encourage supporting behavior within entire workplace. In the present study, we investigated the efficacy of our newly developed educational training program in the management with depression and suicidal risk in the workplace as a single-arm pilot trial. Methods The program is a two-hour (2-h) training course for employees based on the Mental Health First Aid (MHFA) program which aims to increase public mental health literacy. We conducted this program at a company workplace among 91 employees, and ultimately 83 participants completed the self-rated questionnaires. Changes in confidence and practical skills in early intervention of depression and suicide-prevention, and stigma toward mental health problems were evaluated using self-rated questionnaires at 3 time-points; pre-program, immediately post-program, and 1 month after the program. Results Confidence and practical skills were significantly improved even 1 month after the program, and stigma reduced just after the program. Conclusions Our pilot study suggests that the program has a positive impact on encouraging employees to support their co-workers with mental health problems, and is applicable for busy workers due to its short duration. A single-arm design, evaluation using self-rated questionnaire and short-term follow up period are the main limitations of the present study. Hence, future research is required to validate the effects of this program with control groups, and also to assess long-term effectiveness and objective changes such as absenteeism and sick leave..
39. Takahiro A Kato, Comparison of the Defined Daily Dose and Chlorpromazine Equivalent Methods in Antipsychotic Drug Utilization in Six Asian Countries, Neuropsychiatry(London), 8, 6, 1847-1852, 2018.12.
40. Nobuki Kuwano, Takahiro A. Kato, Masato Mitsuhashi, Mina Sato-Kasai, Norihiro Shimokawa, Kohei Hayakawa, Masahiro Ohgidani, Noriaki Sagata, Hiroaki Kubo, Takeshi Sakurai, Shigenobu Kanba, Neuron-related Blood Inflammatory Markers as an Objective Evaluation Tool for Major Depressive Disorder: An Exploratory Pilot Case-Control Study, Journal of Affective Disorders, 10.1016/j.jad.2018.07.040, 240, 88-98, 2018.11.
41. Masaru Tateno, Nikolina Jovanović, Julian Beezhold, Kumi Uehara-Aoyama, Wakako Umene-Nakano, Takashi Nakamae, Naoki Uchida, Naoki Hashimoto, Saya Kikuchi, Yosuke Wake, Daisuke Fujisawa, Keisuke Ikari, Kotaro Otsuka, Katsuyoshi Takahashi, Gaku Okugawa, Norio Watanabe, Tomohiro Shirasaka, Takahiro Kato, Suicidal ideation and burnout among psychiatric trainees in Japan, Early Intervention in Psychiatry, 10.1111/eip.12466, 12, 5, 935-937, 2018.10, Aim: Burnout is a psychological condition that may occur in all workers after being exposed to excessive work-related stresses. We investigated suicidal ideation and burnout among Japanese psychiatric trainees as a part of the Burnout Syndrome Study (BoSS) International. Methods: In the Japanese branch, 91 trainees fully completed suicide ideation and behaviour questionnaire (SIBQ) and Maslach Burnout Inventory—General Survey (MBI-GS). Results: Passive suicidal ideation was reported by 38.5% of Japanese trainees and 22.0% of them had experienced active suicidal ideation. The burnout rate among Japanese subjects was 40.0%. These results were worse compared to the all 1980 trainees who fully completed the main outcome measure in BoSS International, 25.9%, 20.4% and 36.7%, respectively. Conclusions: Our results suggest a higher risk of suicide among Japanese residents. Japan has a higher suicide rate than other countries. Early detection of, and appropriate intervention for, suicidal ideation is important in preventing suicide in psychiatry residents..
42. Yuka Fujii, Yoshito Mizoguchi, Jun Masuoka, yayoi matsuda, Tatsuya Abe, Keizo Anzai, Yutaka Kunitake, Hiroshi Tateishi, Takayoshi Inaba, Toru Murakawa, Takahiro Kato, Akira Monji, Cushing's Syndrome and Psychosis
A Case Report and Literature Review, The primary care companion for CNS disorders, 10.4088/PCC.18br02279, 20, 5, 2018.09, Psychiatric complications of Cushing's syndrome include irritability, anxiety, depressed mood, and cognitive impairment. Psychosis is a rare manifestation of Cushing's syndrome; therefore, the literature on the subject is limited and consists mainly of clinical case reports. We report a case of Cushing's syndrome misdiagnosed as schizophrenia-like psychosis for more than 10 years. Transsphenoidal adenomectomy resulted in amelioration of psychiatric symptoms as well as improvement of cognitive ability. Clinicians should consider the presence of psychiatric symptoms predating the diagnosis of Cushing's syndrome, especially when these symptoms are persistent and treatment-resistant, as seen in the present case..
43. Yukako Nakagami, Hiroaki Kubo, Ryoko Katsuki, Tomomichi Sakai, Genichi Sugihara, Chisako Naito, Hiroyuki Oda, Kohei Hayakawa, Yuriko Suzuki, Daisuke Fujisawa, Naoki Hashimoto, Keiji Kobara, Tetsuji Cho, Hironori Kuga, Kiyoshi Takao, Yoko Kawahara, Yumi Matsumura, Toshiya Murai, Koichi Akashi, Shigenobu Kanba, Kotaro Otsuka, Takahiro Kato, Development of a 2-h suicide prevention program for medical staff including nurses and medical residents
A two-center pilot trial, Journal of Affective Disorders, 10.1016/j.jad.2017.08.074, 225, 569-576, 2018.08, Background Suicide is a crucial global health concern and effective suicide prevention has long been warranted. Mental illness, especially depression is the highest risk factor of suicide. Suicidal risk is increased in people not only with mental illness but also with physical illnesses, thus medical staff caring for physically-ill patients are also required to manage people with suicidal risk. In the present study, we evaluated our newly developed suicide intervention program among medical staff. Methods We developed a 2-h suicide intervention program for medical staff, based on the Mental Health First Aid (MHFA), which had originally been developed for the general population. We conducted this program for 74 medical staff members from 2 hospitals. Changes in knowledge, perceived skills, and confidence in early intervention of depression and suicide-prevention were evaluated using self-reported questionnaires at 3 points; pre-program, immediately after the program, and 1 month after program. Results This suicide prevention program had significant effects on improving perceived skills and confidence especially among nurses and medical residents. These significant effects lasted even 1 month after the program. Limitations Design was a single-arm study with relatively small sample size and short-term follow up. Conclusions The present study suggests that the major target of this effective program is nurses and medical residents. Future research is required to validate the effects of the program with control groups, and also to assess long-term effectiveness and actual reduction in suicide rates..
44. Tateno M*, Tateno Y, Kamikobe C, Monden R, Sakaoka O, Kanazawa J, Kato TA, Saito T, Internet addiction and ADHD traits among female college students in Japan, Journal of the Korean Academy of Child and Adolescent Psychiatry, doi: org/10.5765/jkacap.180011, 29, 3, 144-148, 2018.07.
45. Lucia Lin Liu, Tim M.H. Li, Alan R. Teo, Takahiro Kato, Paul W.C. Wong, Harnessing social media to explore youth social withdrawal in three major cities in China
Cross-sectional web survey, Journal of Medical Internet Research, 10.2196/mental.8509, 20, 5, 2018.05, Background: Socially withdrawn youth belong to an emerging subgroup of youth who are not in employment, education, or training and who have limited social interaction intention and opportunities. The use of the internet and social media is expected to be an alternative and feasible way to reach this group of young people because of their reclusive nature. Objective: The aim of this study was to explore the possibility of using various social media platforms to investigate the existence of the phenomenon of youth social withdrawal in 3 major cities in China. Methods: A cross-sectional open Web survey was conducted from October 2015 to May 2016 to identify and reach socially withdrawn youth in 3 metropolitan cities in China: Beijing, Shanghai, and Shenzhen. To advertise the survey, 3 social media platforms were used: Weibo, WeChat, and Wandianba, a social networking gaming website. Results: In total, 137 participants completed the survey, among whom 13 (9.5%) were identified as belonging to the withdrawal group, 7 (5.1%) to the asocial group, and 9 (6.6%) to the hikikomori group (both withdrawn and asocial for more than 3 months). The cost of recruitment via Weibo was US $7.27 per participant. Conclusions: Several social media platforms in China are viable and inexpensive tools to reach socially withdrawn youth, and internet platforms that specialize in a certain culture or type of entertainment appeared to be more effective in reaching socially withdrawn youth..
46. Takahiro Kato, Shigenobu Kanba, Is a socio-cultural analysis of depressive disorders a matter of concern? Response to Kaiya, American Journal of Psychiatry, 10.1176/appi.ajp.2018.17121404r, 175, 5, 483-484, 2018.05.
47. Alan R. Teo, Jason I. Chen, Hiroaki Kubo, Ryoko Katsuki, Mina Sato-Kasai, Norihiro Shimokawa, Kohei Hayakawa, Wakako Umene-Nakano, James E. Aikens, Shigenobu Kanba, Takahiro A Kato, Development and validation of the 25-item Hikikomori Questionnaire (HQ-25), Psychiatry and Clinical Neurosciences, 10.1111/pcn.12691, 2018.05, Aim: Hikikomori, a form of severe social withdrawal, is an emerging issue in mental health, for which validated measurement tools are lacking. The object was to develop a self-report scale of hikikomori, and assess its psychometric properties and diagnostic accuracy. Methods: A sample of 399 participants from clinical and community settings completed measures. Psychometric properties were assessed with factor analysis; diagnostic accuracy was compared against a semi-structured diagnostic interview. Results: The Hikikomori Questionnaire contained 25 items across three subscales representing socialization, isolation, and emotional support. Internal consistency, test-retest reliability, and convergent validity were all satisfactory. The area under the curve was 0.86 (95% confidence interval, 0.80-0.92). A cut-off score of 42 (out of 100) was associated with a sensitivity of 94%, specificity of 61%, and positive predictive value of 17%. Conclusion: The 25-item Hikikomori Questionnaire (HQ-25) possesses robust psychometric properties and diagnostic accuracy in an initial sample of Japanese adults. Additional research on its psychometric properties and ability to support clinical assessment of hikikomori is warranted..
48. Nobuki Kuwano, Takahiro Kato, Daiki Setoyama, Mina Sato-Kasai, Norihiro Shimokawa, Kohei Hayakawa, Masahiro Ohgidani, Noriaki Sagata, Hiroaki Kubo, Junji Kishimoto, Dongchon Kang, Shigenobu Kanba, Tryptophan-kynurenine and lipid related metabolites as blood biomarkers for first-episode drug-naïve patients with major depressive disorder
An exploratory pilot case-control study, Journal of Affective Disorders, 10.1016/j.jad.2018.01.014, 231, 74-82, 2018.04, Background: 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. Methods: 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. Results: 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 (HDL-C) was the predictive biomarker for severity of depression in MDD group (R2 = 0.444). Interestingly, depressive symptoms were variously correlated with plasma tryptophan-kynurenine and lipid related metabolites. Moreover, plasma tryptophan-kynurenine metabolites and cholesteryl esters (CEs) were significantly correlated in MDD group, but not in HC group. Limitations: This study had small sample size, and we did not use the multiple test correction. Conclusions: This is the first study to suggest that not only tryptophan-kynurenine metabolites but also HDL-C and CEs are important blood biomarkers for first-episode drug-naïve MDD patients. The present study sheds new light on early intervention in clinical practice in depression, and further clinical studies especially large-scale prospective studies are warranted..
49. Kohei Hayakawa, Takahiro Kato, Motoki Watabe, Alan R. Teo, Hideki Horikawa, Nobuki Kuwano, Norihiro Shimokawa, Mina Sato-Kasai, Hiroaki Kubo, Masahiro Ohgidani, Noriaki Sagata, Hiroyuki Toda, Masaru Tateno, Naotaka Shinfuku, Junji Kishimoto, Shigenobu Kanba, Blood biomarkers of Hikikomori, a severe social withdrawal syndrome, Scientific Reports, 10.1038/s41598-018-21260-w, 8, 1, 2018.02, Hikikomori, a severe form of social withdrawal syndrome, is a growing social issue in Japan and internationally. The pathophysiology of hikikomori has not yet been elucidated and an effective treatment remains to be established. Recently, we revealed that avoidant personality disorder is the most common comorbidity of hikikomori. Thus, we have postulated that avoidant personality is the personality underpinning hikikomori. First, we herein show relationships between avoidant personality traits, blood biomarkers, hikikomori-related psychological features, and behavioural characteristics assessed by a trust game in non-hikikomori volunteers. Avoidant personality traits were negatively associated with high-density lipoprotein cholesterol (HDL-C) and uric acid (UA) in men, and positively associated with fibrin degeneration products (FDP) and high sensitivity C-reactive protein (hsCRP) in women. Next, we recruited actual individuals with hikikomori, and compared avoidant personality traits, blood biomarkers, and psychological features between individuals with hikikomori and age-matched healthy controls. Individuals with hikikomori had higher avoidant personality scores in both sexes, and showed lower serum UA levels in men and lower HDL-C levels in women compared with healthy controls. This is the first report showing possible blood biomarkers for hikikomori, and opens the door to clarify the underlying biological pathophysiology of hikikomori..
50. Yohei Minami, Noriyuki Sonoda, Eiichi Hayashida, Hiroaki Makimura, Makoto Ide, Noriko Ikeda, Masahiro Ohgidani, Takahiro Kato, Yoshihiro Seki, Yasutaka Maeda, Shigenobu Kanba, Ryoichi Takayanagi, Yoshihiro Ogawa, Toyoshi Inoguchi, P66Shc Signaling Mediates Diabetes-Related Cognitive Decline, Scientific Reports, 10.1038/s41598-018-21426-6, 8, 1, 2018.02, Accumlating evidence have suggested that diabetes mellitus links dementia, notably of Alzheimer's disease (AD). However, the underlying mechanism remains unclear. Several studies have shown oxidative stress (OS) to be one of the major factors in the pathogenesis of diabetic complications. Here we show OS involvement in brain damage in a diabetic animal model that is at least partially mediated through an AD-pathology-independent mechanism apart from amyloid-β accumulation. We investigated the contribution of the p66Shc signaling pathway to diabetes-related cognitive decline using p66Shc knockout (-/-) mice. p66Shc (-/-) mice have less OS in the brain and are resistant to diabetes-induced brain damage. Moreover, p66Shc (-/-) diabetic mice show significantly less cognitive dysfunction and decreased levels of OS and the numbers of microglia. This study postulates a p66Shc-mediated inflammatory cascade leading to OS as a causative pathogenic mechanism in diabetes-associated cognitive impairment that is at least partially mediated through an AD-pathology-independent mechanism..
51. Takahiro Kato, Shigenobu Kanba, Alan R. Teo, Hikikomori
experience in Japan and international relevance, World Psychiatry, 10.1002/wps.20497, 17, 1, 105-106, 2018.02, 九州大学を拠点するひきこもり国際共同ネットワークによる成果の概要をまとめた報告である。.
52. Masaru Tateno, Alan R. Teo, Takahiro Kato, Does LINE addiction exist? Potential concerns about Japan's most popular form of social media on smartphones, Psychiatry and Clinical Neurosciences, 10.1111/pcn.12672, 2018.01.
53. Tomonari Fujita, Yoshito Mizoguchi, Yutaka Kunitake, Hiroshi Tateishi, Takayoshi Inaba, Takahiro Kato, Akira Monji, Second-generation antipsychotic-induced hypoglycemia, The primary care companion for CNS disorders, 10.4088/PCC.17br02186, 20, 1, 2018.01, Complaints of hypoglycemia resemble the sedative effect of antipsychotics. As such, clinicians may overlook hypoglycemia in patients with psychiatric disorders. Here, a case of hypoglycemia associated with hyperinsulinemia induced by quetiapine in a female patient with bipolar disorder is reported. The case suggests that clinicians should be aware of the potential for hypoglycemia induced by second-generation antipsychotics..
54. Takayoshi Inaba, Rintaro Sogawa, Yoshito Mizoguchi, Hiroshi Tateishi, Yutaka Kunitake, Takahiro Kato, Akira Monji, Lamotrigine rechallenge in treatment-resistant bipolar disorder, The primary care companion for CNS disorders, 10.4088/PCC.17m02231, 20, 2, 2018.01, Background: Although lamotrigine may be useful for treating patients with treatment-resistant bipolar disorder, some lamotrigine-associated adverse effects, including mild to moderate skin rash, may prevent the continuation of treatment. Methods: We investigated lamotrigine rechallenge for the treatment of bipolar disorder. The present study was based on retrospective chart review of outpatients with bipolar disorder (DSM-5 criteria) who visited the hospital’s psychiatric department between July 2011 and August 2017. The review revealed 12 patients with bipolar disorder who underwent lamotrigine rechallenge following lamotrigine discontinuation due to various adverse reactions, including skin rash. None of the patients showed Stevens-Johnson syndrome. All patients suffered from treatment-resistant bipolar disorder that was refractory to treatments other than lamotrigine. For each patient, the severity of the adverse reaction to lamotrigine was weighed against the potential for therapeutic benefit. Results: In 9 of 12 cases, a positive outcome of lamotrigine rechallenge was observed. In all cases with initial skin rash with very slow titration of lamotrigine, rechallenge was successful with no recurrence of the rash. In the 3 cases for which lamotrigine was unsuccessful, lamotrigine was discontinued owing to movement disorders, ie, oral dyskinesia and action tremor, and liver dysfunction, respectively. Conclusions: The present results suggest that lamotrigine rechallenge may be a viable option for treatment-resistant bipolar disorder..
55. Masaru Tateno, Alan R. Teo, Masaki Shiraishi, Masaya Tayama, Chiaki Kawanishi, Takahiro Kato, Prevalence rate of Internet addiction among Japanese college students
Two cross-sectional studies and reconsideration of cut-off points of Young's Internet Addiction Test in Japan, Psychiatry and Clinical Neurosciences, 10.1111/pcn.12686, 2018.01, Aim: Due to variation in estimates of the prevalence of Internet addiction (IA) in prior research, we conducted two cross-sectional studies over 2years investigating the prevalence rate of IA in college students in Japan and reconsidered appropriate cut-off points of a self-rating scale to screen possible IA. Methods: This study was composed of two parts: survey I in 2014 and survey II in 2016, which were conducted in the same schools with an interval of 2years. The study questionnaire included questions about demographics and Internet use, and Young's Internet Addiction Test (IAT). Additionally, the subjects in survey II were asked about self-reported IA. Results: There were 1005 respondents in total with a mean age (± SD) of 18.9±1.3 years. The mean IAT scores remained stable between 2014 and 2016: 45.2±12.6 in survey I and 45.5±13.1 in survey II (overall mean IAT score of 45.4±13.0). With respect to self-reported IA in survey II, a total of 21.6% admitted to having IA (score of 5 or 6 on a 6-point Likert scale). We categorized these subjects as IA, and the remainder as non-IA. The mean IAT score showed a significant difference between these two groups (57.8±14.3 vs 42.1±10.7, P<0.001). Conclusion: The severity of IA symptoms among Japanese college students has appeared stable in recent years, with mean IAT scores of over 40. Our results suggest that a screening score cut-off of 40 on the IAT could be reconsidered and that 50 might be proposed for the cut-off..
56. Satoshi Akamine, Noriaki Sagata, Yasunari Sakai, Takahiro Kato, Takeshi Nakahara, Yuki Matsushita, Osamu Togao, Hiwatashi Akio, Masafumi Sanefuji, Yoshito Ishizaki, Hiroyuki Torisu, Hirotomo Saitsu, Naomichi Matsumoto, Toshiro Hara, Akira Sawa, Shinichi Kano, Masutaka Furue, Shigenobu Kanba, Chad A. Shaw, Shoichi Ohga, Early-onset epileptic encephalopathy and severe developmental delay in an association with de novo double mutations in NF1 and MAGEL2, Epilepsia Open, 10.1002/epi4.12085, 3, 1, 81-85, 2018.01, 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 in NF1 and the Schaaf-Yang syndrome-associated gene, MAGEL2. 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 that neuronal cells from 9 patients with NF1 expressed significantly lower levels of MAGEL2 (54%, p = 0.0047) than those from healthy individuals. These data provide the first evidence that pathogenic mutations of NF1 deregulate the expression of other neurodevelopmental disease-associated genes. De novo mutations in multiple genes may lead to severe developmental phenotypes through their cumulative effects or synergistic interactions..
57. Yu Tao Xiang, Takahiro Kato, Taishiro Kishimoto, Gabor S. Ungvari, Helen F.K. Chiu, Tian Mei Si, Shu Yu Yang, Senta Fujii, Chee H. Ng, Naotaka Shinfuku, Comparison of treatment patterns in schizophrenia between China and Japan (2001-2009), Asia-Pacific Psychiatry, 10.1111/appy.12277, 9, 4, 2017.12, Introduction: To date no study has compared the treatment patterns for schizophrenia specifically between China and Japan. This study examined the cross-national differences in the use of psychotropic drugs and electroconvulsive therapy (ECT) in schizophrenia. Method: Data on 3248 schizophrenia inpatients (n = 1524 in China and n = 1724 in Japan) were collected by either chart review or interviews during the designated 3 study periods between 2001 and 2009. Patients' socio-demographic and clinical characteristics, prescriptions of psychotropic drugs, and ECT use were recorded using a standardized protocol and data collection procedure. Results: Multivariate analyses revealed that compared to their Japanese counterparts, Chinese inpatients had a shorter length of current hospitalization, were significantly less frequently prescribed second-generation antipsychotics (except clozapine), antipsychotic polypharmacy, benzodiazepines, and mood stabilizers, and more likely to receive clozapine, antidepressants, and ECT. Discussion: Substantial variations in inpatient treatment patterns for schizophrenia were found between China and Japan. The common use of ECT and clozapine in Chinese inpatients and the frequent use of antipsychotic polypharmacy and high antipsychotic doses in Japanese inpatients need to be addressed..
58. Paul W.C. Wong, Lucia L. Liu, Tim M.H. Li, Takahiro Kato, Alan R. Teo, Does hikikomori (severe social withdrawal) exist among young people in urban areas of China?, Asian Journal of Psychiatry, 10.1016/j.ajp.2017.10.026, 30, 175-176, 2017.12.
59. Yoshinori Haraguchi, Yoshito Mizoguchi, Masahiro Ohgidani, Yoshiomi Imamura, Toru Murakawa-Hirachi, Hiromi Nabeta, Hiroshi Tateishi, Takahiro Kato, Akira Monji, Donepezil suppresses intracellular Ca2+ mobilization through the PI3K pathway in rodent microglia, Journal of Neuroinflammation, 10.1186/s12974-017-1033-0, 14, 1, 2017.12, Background: 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 Ca2+ signaling is important for microglial functions such as release of NO and cytokines. In addition, alteration of intracellular Ca2+ signaling underlies the pathophysiology of AD, while it remains unclear how donepezil, an acetylcholinesterase inhibitor, affects intracellular Ca2+ mobilization in microglial cells. Methods: We examined whether pretreatment with donepezil affects the intracellular Ca2+ mobilization using fura-2 imaging and tested the effects of donepezil on phagocytic activity by phagocytosis assay in rodent microglial cells. Results: In this study, we observed that pretreatment with donepezil suppressed the TNFα-induced sustained intracellular Ca2+ elevation in both rat HAPI and mouse primary microglial cells. On the other hand, pretreatment with donepezil did not suppress the mRNA expression of both TNFR1 and TNFR2 in rodent microglia we used. Pretreatment with acetylcholine but not donepezil suppressed the TNFα-induced intracellular Ca2+ elevation through the nicotinic α7 receptors. In addition, sigma 1 receptors were not involved in the donepezil-induced suppression of the TNFα-mediated intracellular Ca2+ elevation. Pretreatment with donepezil suppressed the TNFα-induced intracellular Ca2+ elevation through the PI3K pathway in rodent microglial cells. Using DAF-2 imaging, we also found that pretreatment with donepezil suppressed the production of NO induced by TNFα treatment and the PI3K pathway could be important for the donepezil-induced suppression of NO production in rodent microglial cells. Finally, phagocytosis assay showed that pretreatment with donepezil promoted phagocytic activity of rodent microglial cells through the PI3K but not MAPK/ERK pathway. Conclusions: These suggest that donepezil could directly modulate the microglial function through the PI3K pathway in the rodent brain, which might be important to understand the effect of donepezil in the brain..
60. Noriaki Sagata, Takahiro Kato, Shin Ichi Kano, Masahiro Ohgidani, Norihiro Shimokawa, Mina Sato-Kasai, Kohei Hayakawa, Nobuki Kuwano, Ashley M. Wilson, Koko Ishizuka, Shiori Kato, Takeshi Nakahara, Makiko Nakahara-Kido, Daiki Setoyama, Yasunari Sakai, Shoichi Ohga, Masutaka Furue, Akira Sawa, Shigenobu Kanba, Dysregulated gene expressions of MEX3D, FOS and BCL2 in human induced-neuronal (iN) cells from NF1 patients
A pilot study, Scientific Reports, 10.1038/s41598-017-14440-7, 7, 1, 2017.12, Direct conversion technique to produce induced-neuronal (iN) cells from human fibroblasts within 2 weeks is expected to discover unknown neuronal phenotypes of neuropsychiatric disorders. Here, we present unique gene expression profiles in iN cells from patients with neurofibromatosis type 1 (NF1), a single-gene multifaceted disorder with comparatively high co-occurrence of autism spectrum disorder (ASD). Microarray-based transcriptomic analysis on iN cells from male healthy controls and male NF1 patients (NF1-iN cells) revealed that 149 genes expressions were significantly different (110 upregulated and 39 downregulated). We validated that mRNA of MEX3D (mex-3 RNA binding family member D) was lower in NF1-iN cells by real-time PCR with 12 sex-mixed samples. In NF1-iN cells on day 14, higher expression of FOS mRNA was observed with lower expression of MEX3D mRNA. Interestingly, BCL2 mRNA was higher in NF1-iN cells on day 5 (early-period) but not on day 14. Our data suggest that aberrant molecular signals due to NF1 mutations may disturb gene expressions, a subset of which defines continuum of the neuronal phenotypes of NF1 with ASD. Further translational studies using induced pluripotent stem (iPS) cell-derived neuronal cells are needed to validate our preliminary findings especially confirming meanings of analysis using early-period iN cells..
61. Masahiro Ohgidani, Takahiro Kato*, Masako Hosoi, Tsuda Makoto, Kohei Hayakawa, Chie Hayaki, Rie Iwaki, Noriaki Sagata, Ryota Hashimoto, Kazuhide Inoue, Nobuyuki Sudo, Shigenobu Kanba, Fibromyalgia and microglial TNF-α
Translational research using human blood induced microglia-like cells, Scientific Reports, 10.1038/s41598-017-11506-4, 7, 1, 2017.12, Fibromyalgia is a refractory disease characterized by chronic intractable pain and psychological suffering, the cause of which has not yet been elucidated due to its complex pathology. Activation of immune cells in the brain called microglia has attracted attention as a potential underlying pathological mechanism in chronic pain. Until recently, however, technological and ethical considerations have limited the ability to conduct research using human microglia. To overcome this limitation, we have recently developed a technique to create human-induced microglia-like (iMG) cells from human peripheral blood monocytes. In this study, we created the iMG cells from 14 patients with fibromyalgia and 10 healthy individuals, and compared the activation of iMG cells between two groups at the cellular level. The expression of tumor necrosis factor (TNF)-α at mRNA and protein levels significantly increased in ATP-stimulated iMG cells from patients with fibromyalgia compared to cells from healthy individuals. Interestingly, there was a moderate correlation between ATP-induced upregulation of TNF-α expression and clinical parameters of subjective pain and other mental manifestations of fibromyalgia. These findings suggest that microglia in patients with fibromyalgia are hypersensitive to ATP. TNF-α from microglia may be a key factor underlying the complex pathology of fibromyalgia..
62. Takahiro Kato*, Shigenobu Kanba, Modern-type depression as an "adjustment" disorder in Japan
The intersection of collectivistic society encounteringanindividualisticperformance-basedsystem, American Journal of Psychiatry, 10.1176/appi.ajp.2017.17010059, 174, 11, 1051-1053, 2017.11, うつ病の現代における課題に関して、特に適応の障害という観点から論じた論文である。.
63. Takahiro Kato, Masahiro Ohgidani, Shigenobu Kanba, Translational research on neuropsychiatrie disorders
Focusing on microglia hypothesis, Brain and Nerve, 69, 9, 1007-1015, 2017.09, 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)..
64. Yutaka Kunitake, Yoshito Mizoguchi, Rintaro Sogawa, Jun Matsushima, Takahiro Kato, Toshiro Kawashima, Akira Monji, Effect of excessive coffee consumption on the clinical course of a patient with bipolar disorder
A case report and literature review, Clinical Neuropharmacology, 10.1097/WNF.0000000000000222, 40, 4, 160-162, 2017.07, Objective The aim of this study was to examine the impact of excessive caffeine consumption on therapeutic outcomes in bipolar disorder. Methods and Results We report on a case of a patient with bipolar disorder whose psychiatric symptoms were ameliorated with the elevation of lithium concentrations after the reduction of excessive daily coffee consumption, and we review the relevant literatures. Conclusions Excessive coffee consumption may exacerbate the therapeutic course of bipolar disorder through its effects on the mechanisms underlying bipolar disorder itself, as well as by affecting the blood concentration of lithium..
65. Kohei Hayakawa, Takahiro Kato, Shigeru Imamura, Naofumi Kasai, Shigenobu Kanba, Progressive brain atrophy and cognitive decline along with multiple episodes of delirium, Psychiatry and Clinical Neurosciences, 10.1111/pcn.12527, 71, 6, 418-419, 2017.06.
66. Daisuke Ikawa, Manabu Makinodan, Keiko Iwata, Masahiro Ohgidani, Takahiro Kato, Yasunori Yamashita, Kazuhiko Yamamuro, Sohei Kimoto, Michihiro Toritsuka, Takahira Yamauchi, Shin ichi Fukami, Hiroki Yoshino, Kazuki Okumura, Tatsuhide Tanaka, Akio Wanaka, Yuji Owada, Masatsugu Tsujii, Toshiro Sugiyama, Kenji Tsuchiya, Norio Mori, Ryota Hashimoto, Hideo Matsuzaki, Shigenobu Kanba, Toshifumi Kishimoto, Microglia-derived neuregulin expression in psychiatric disorders, Brain, Behavior, and Immunity, 10.1016/j.bbi.2017.01.003, 61, 375-385, 2017.03, 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 translate these findings for application in clinical psychiatry, we measured levels of NRG1 splice-variant expression in clinically available PBMCs of patients with ASD. Levels of NRG1 type III expression in PBMCs were positively correlated with impairments in social interaction in children with ASD (as assessed using the Autistic Diagnostic Interview-Revised test: ADI-R). These findings suggest that immune cell-derived NRGs may be implicated in the pathobiology of psychiatric disorders such as ASD..
67. Masahiro Ohgidani, Takahiro Kato, Yoshinori Haraguchi, Toshio Matsushima, Yoshito Mizoguchi, Toru Murakawa-Hirachi, Noriaki Sagata, Akira Monji, Shigenobu Kanba, Microglial CD206 gene has potential as a state marker of bipolar disorder, Frontiers in Immunology, 10.3389/fimmu.2016.00676, 7, JAN, 2017.01, 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 depressive states. The profiling pattern of case 1 showed that M1 microglia is dominant in the manic state compared to the depressive state. However, the patterns of cases 2 and 3 were not consistent with the pattern of case 1. CD206, a mannose receptor known as a typical M2 marker, was significantly downregulated in the manic state among all three patients. This is the first report to indicate the importance of shifting microglial M1/M2 characteristics, especially the CD206 gene expression pattern between depressive and manic states. Further translational studies are needed to dig up the microglial roles in the underlying biological mechanisms of bipolar disorder..
68. Takahiro Kato, Alan R. Teo, Masaru Tateno, Motoki Watabe, Hiroaki Kubo, Shigenobu Kanba, Can Pokémon GO rescue shut-ins (hikikomori) from their isolated world?, Psychiatry and Clinical Neurosciences, 10.1111/pcn.12481, 71, 1, 75-76, 2017.01.
69. Mina Sato-Kasai, Takahiro Kato, Masahiro Ohgidani, Yoshito Mizoguchi, Noriaki Sagata, Shogo Inamine, Hideki Horikawa, Kohei Hayakawa, Norihiro Shimokawa, Sota Kyuragi, Yoshihiro Seki, Akira Monji, Shigenobu Kanba, Aripiprazole inhibits polyI
C-induced microglial activation possibly via TRPM7, Schizophrenia Research, 10.1016/j.schres.2016.08.022, 178, 1-3, 35-43, 2016.12, Viral infections during fetal and adolescent periods, as well as during the course of schizophrenia itself have been linked to the onset and/or relapse of a psychosis. We previously reported that the unique antipsychotic aripiprazole, a partial D2 agonist, inhibits the release of tumor necrosis factor (TNF)-α from interferon-γ-activated rodent microglial cells. Polyinosinic-polycytidylic acid (polyI:C) has recently been used as a standard model of viral infections, and recent in vitro studies have shown that microglia are activated by polyI:C. Aripiprazole has been reported to ameliorate behavioral abnormalities in polyI:C-induced mice. To clarify the anti-inflammatory properties of aripiprazole, we investigated the effects of aripiprazole on polyI:C-induced microglial activation in a cellular model of murine microglial cells and possible surrogate cells for human microglia. PolyI:C treatment of murine microglial cells activated the production of TNF-α and enhanced the p38 mitogen-activated protein kinase (MAPK) pathway, whereas aripiprazole inhibited these responses. In addition, polyI:C treatment of possible surrogate cells for human microglia markedly increased TNF-α mRNA expression in cells from three healthy volunteers. Aripiprazole inhibited this increase in cells from two individuals. PolyI:C consistently increased intracellular Ca2 + concentration ([Ca2 +]i) in murine microglial cells by influx of extracellular Ca2 +. We demonstrated that transient receptor potential in melastatin 7 (TRPM7) channels contributed to this polyI:C-induced increase in [Ca2 +]i. Taken together, these data suggest that aripiprazole may be therapeutic for schizophrenia by reducing microglial inflammatory reactions, and TRPM7 may be a novel therapeutic target for schizophrenia. Further studies are needed to validate these findings..
70. Masaru Tateno, Alan R. Teo, Tomohiro Shirasaka, Masaya Tayama, Motoki Watabe, Takahiro A. Kato, Internet addiction and self-evaluated attention-deficit hyperactivity disorder traits among Japanese college students, Psychiatry and clinical neurosciences, 10.1111/pcn.12454, 70, 12, 567-572, 2016.12, Aim: 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. Methods: Severity of IA and ADHD traits was assessed by self-report scales. Subjects were 403 college students (response rate 78%) who completed a questionnaire including Young's Internet Addiction Test (IAT) and the Adult ADHD Self-Report Scale–V1.1. Results: Out of 403 subjects, 165 were male. The mean age was 18.4 ± 1.2 years, 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 40–69), and 15 (3.7%) had severe addiction (IAT ≥ 70). Mean length of Internet use was 4.1 ± 2.8 h/day on weekdays and 5.9 ± 3.7 h/day on the weekend. Females used the Internet mainly for social networking services while males preferred online games. Students with a positive ADHD screen scored significantly higher on the IAT than those negative for ADHD screen (50.2 ± 12.9 vs 43.3 ± 12.0). Conclusion: Our results suggest that Internet misuse may be related to ADHD traits among Japanese youth. Further investigation of the links between IA and ADHD is warranted..
71. Daiki Setoyama, Takahiro A. Kato, Ryota Hashimoto, Hiroshi Kunugi, Kotaro Hattori, Kohei Hayakawa, Mina Sato-Kasai, Norihiro Shimokawa, Sachie Kaneko, Sumiko Yoshida, Yu Ichi Goto, Yuka Yasuda, Hidenaga Yamamori, Masahiro Ohgidani, Noriaki Sagata, Daisuke Miura, Dongchon Kang, Shigenobu Kanba, Plasma metabolites predict severity of depression and suicidal ideation in psychiatric patients-a multicenter pilot analysis, PloS one, 10.1371/journal.pone.0165267, 11, 12, 2016.12, 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-aminobutyric acid (GABA)) are commonly associated with SOD in all three independent cohort sets regardless of the presence or absence of medication and diagnostic difference. In addition, we have shown several metabolites are independently associated with sub-symptoms of depression including SI. We successfully created a classification model to discriminate depressive patients with or without SI by machine learning technique. Finally, we produced a pilot algorithm to predict a grade of SI with citrate and kynurenine. The above metabolites may have strongly been associated with the underlying novel biological pathophysiology of SOD. We should explore the biological impact of these metabolites on depressive symptoms by utilizing a cross species study model with human and rodents. The present multicenter pilot study offers a potential utility for measuring blood metabolites as a novel objective tool for not only assessing SOD but also evaluating therapeutic efficacy in clinical practice. In addition, modification of these metabolites by diet and/or medications may be a novel therapeutic target for depression. To clarify these aspects, clinical trials measuring metabolites before/after interventions should be conducted. Larger cohort studies including non-clinical subjects are also warranted to clarify our pilot findings..
72. Masaru Tateno, Norbert Skokauskas, Takahiro A. Kato, Alan R. Teo, Anthony P.S. Guerrero, New game software (Pokémon Go) may help youth with severe social withdrawal, hikikomori, Psychiatry research, 10.1016/j.psychres.2016.10.038, 246, 848-849, 2016.12.
73. Joji Maruo, Yoshinori Haraguchi, Hiroshi Tateishi, Tomoyuki Noguchi, Yoshito Mizoguchi, Takahiro A. Kato, Toshiro Kawashima, Akira Monji, Abnormal behaviours during pramipexole treatment for Cotard's syndrome
a case report, Psychogeriatrics, 10.1111/psyg.12148, 16, 4, 283-286, 2016.07, Cotard's syndrome is a relatively rare condition that involves a delusion of negation in which an individual believes he or she has lost his or her soul, is dead, or is without functional body systems. This syndrome is observed in various neuropsychiatric disorders but most commonly in mood disorders. Pramipexole has often been used in the adjunctive treatment of both bipolar and unipolar depression, and it is known to cause rare but serious adverse effects such as compulsive behaviours in the treatment of Parkinson's disease. Here we report a case of Cotard's syndrome in treatment-resistant major depression associated with abnormal behaviours that might be caused by pramipexole. In the present case, the patient's abnormal behaviours gradually disappeared about 2 months after the discontinuation of pramipexole. The hypoperfusion in the bilateral parieto-occipital lobe found on single-photon emission computed tomography suggests the presence of Lewy body disease pathology. Nonetheless, the patient's abnormal behaviours disappeared after the discontinuation of pramipexole, indicating that they are mainly attributable to pramipexole treatment. However, the possible existence of Lewy body pathology could facilitate the emergence of abnormal behaviours after treatment with pramipexole. The patient's abnormal behaviours, such as eating other patients' food and taking her medicine before the scheduled time, might differ from typical compulsive behaviours induced by pramipexole (such as pathological gambling and hypersexuality), but they could be regarded as disinhibition. Therefore, we should follow up on the clinical course of this case carefully through neuroimaging investigation and neurocognitive assessment..
74. Yoshinori Haraguchi, Yoshito Mizoguchi, Tomoyuki Noguchi, Takeo Arai, Junko Fukuyama, Takahiro A. Kato, Toshiro Kawashima, Akira Monji, A patient with Alzheimer's disease complicated by elderly-onset Cushing's syndrome who had undergone surgical treatment for adrenocorticotropic hormone-independent macronodular adrenal hyperplasia, Psychogeriatrics, 10.1111/psyg.12146, 16, 4, 274-276, 2016.07, 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..
75. Masahiro Ohgidani, Takahiro A. Kato, Noriaki Sagata, Kohei Hayakawa, Norihiro Shimokawa, Mina Sato-Kasai, Shigenobu Kanba, TNF-α from hippocampal microglia induces working memory deficits by acute stress in mice, Brain, Behavior, and Immunity, 10.1016/j.bbi.2015.08.022, 55, 17-24, 2016.07, The role of microglia in stress responses has recently been highlighted, yet the underlying mechanisms of action remain unresolved. The present study examined disruption in working memory due to acute stress using the water-immersion resistant stress (WIRS) test in mice. Mice were subjected to acute WIRS, and biochemical, immunohistochemical, and behavioral assessments were conducted. Spontaneous alternations (working memory) significantly decreased after exposure to acute WIRS for 2 h. We employed a 3D morphological analysis and site- and microglia-specific gene analysis techniques to detect microglial activity. Morphological changes in hippocampal microglia were not observed after acute stress, even when assessing ramification ratios and cell somata volumes. Interestingly, hippocampal tumor necrosis factor (TNF)-α levels were significantly elevated after acute stress, and acute stress-induced TNF-α was produced by hippocampal-ramified microglia. Conversely, plasma concentrations of TNF-α were not elevated after acute stress. Etanercept (TNF-α inhibitor) recovered working memory deficits in accordance with hippocampal TNF-α reductions. Overall, results suggest that TNF-α from hippocampal microglia is a key contributor to early-stage stress-to-mental responses..
76. Takahiro A. Kato, Shigenobu Kanba, Alan R. Teo, A 39-year-old "adultolescent"
Understanding social withdrawal in Japan, American Journal of Psychiatry, 10.1176/appi.ajp.2015.15081034, 173, 2, 112-114, 2016.02.
77. Takahiro A. Kato, Shigenobu Kanba, Boundless syndromes in modern society
An interconnected world producing novel psychopathology in the 21st century, Psychiatry and clinical neurosciences, 10.1111/pcn.12368, 70, 1, 1-2, 2016.01.
78. Naoki Hashimoto, Yuriko Suzuki, Takahiro A. Kato, Daisuke Fujisawa, Ryoko Sato, Kumi Aoyama-Uehara, Maiko Fukasawa, Satoshi Asakura, Ichiro Kusumi, Kotaro Otsuka, Effectiveness of suicide prevention gatekeeper-training for university administrative staff in Japan, Psychiatry and clinical neurosciences, 10.1111/pcn.12358, 70, 1, 62-70, 2016.01, Aims Suicide is 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. However, no studies have investigated the effectiveness of such programs in university settings in Japan. The aim of this study was to investigate the effectiveness of the gatekeeper-training program for administrative staff in Japanese universities. Methods We developed a 2.5-h gatekeeper-training program based on the Mental Health First Aid program, which was originally developed for the general public. Seventy-six administrative staff at 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. Results We found a significant improvement in competence in the management of suicidal students. We also found improvements in confidence in management of suicidal students and behavioral intention as a gatekeeper after training, though questionnaires for those secondary outcomes were not validated. These improvements continued for a month. About 95% of the participants rated the program as useful or very useful and one-third of the participants had one or more chances to utilize their skills within a month. Conclusions The current results suggest the positive effects of the training program in university settings in Japan. Future evaluation that includes comparison with standard didactic trainings and an assessment of long-term effectiveness are warranted..
79. Hiroshi Tateishi, Toru Hirachi, Joji Maruo, Yoshinori Haraguchi, Tomoyuki Noguchi, Yoshito Mizoguchi, Takahiro A. Kato, Toshiro Kawashima, Akira Monji, Neurocognitive Disorders in Chronic Kidney Disease
A Case Report and Literature Review, Psychosomatics, 10.1016/j.psym.2015.07.007, 57, 1, 107-112, 2016.01.
80. T. Hirachi, H. Ishii, Y. Tada, T. Noguchi, Y. Haraguchi, H. Tateishi, Y. Mizoguchi, T. A. Kato, T. Kawashima, A. Monji, Mania occurring during systemic lupus erythematosus relapse and its amelioration on clinical and neuroimaging follow-up, Lupus, 10.1177/0961203315570161, 24, 9, 990-993, 2015.08, Psychiatric manifestations of systemic lupus erythematosus (SLE) that are commonly preceded by organic syndromes include confusional states, anxiety disorder, cognitive dysfunction, mood disorder and psychosis. A 35-year-old woman was admitted to hospital with a relapse of SLE. Laboratory data were exacerbated, with some physical symptoms, and her primary psychiatric symptom was mania. The symptoms were reduced by treatment with prednisolone, methylprednisolone and aripiprazole. Magnetic resonance imaging and single-photon emission computed tomography (SPECT) using 123I-IMP was then performed and analyzed with three-dimensional stereotactic surface projection. This case emphasizes that SLE can commence with organic syndromes and relapse with predominantly psychiatric symptoms, and that the treatment efficacy may be confirmed using a follow-up of SPECT..
81. Alan R. Teo, Kyle Stufflebam, Somnath Saha, Michael D. Fetters, Masaru Tateno, Shigenobu Kanba, Takahiro A. Kato, Psychopathology associated with social withdrawal
Idiopathic and comorbid presentations, Psychiatry research, 10.1016/j.psychres.2015.04.033, 228, 1, 182-183, 2015.07.
82. Paul C. Guest, Keiko Iwata, Takahiro A. Kato, Johann Steiner, Andrea Schmitt, Christoph W. Turck, Daniel Martins-De-Souza, MK-801 treatment affects glycolysis in oligodendrocytes more than in astrocytes and neuronal cells
Insights for schizophrenia, Frontiers in Cellular Neuroscience, 10.3389/fncel.2015.00180, 9, MAY, 2015.05, 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 oligodendrocytes, which had altered levels of hexokinase 1 (HK1), enolase 2 (ENO2), phosphoglycerate kinase (PGK), and phosphoglycerate mutase 1 after acute MK-801 treatment (8 h), and HK1, ENO2, PGK, and triosephosphate isomerase (TPI) following long term treatment (72 h). Addition of the antipsychotic clozapine to the cultures resulted in counter-regulatory effects to the MK-801 treatment by normalizing the levels of ENO2 and PGK in both the acute and long term cultures. In astrocytes, MK-801 affected only aldolase C (ALDOC) under both acute conditions and HK1 and ALDOC following long term treatment, and TPI was the only enzyme affected under long term conditions in the neuronal cells. In conclusion, MK-801 affects glycolysis in oligodendrocytes to a larger extent than neuronal cells and this may be modulated by antipsychotic treatment. Although cell culture studies do not necessarily reflect the in vivo pathophysiology and drug effects within the brain, these results suggest that neurons, astrocytes, and oligodendrocytes are affected differently in schizophrenia. Employing in vitro models using neurotransmitter agonists and antagonists may provide new insights about the pathophysiology of schizophrenia which could lead to a novel system for drug discovery..
83. Takahiro A. Kato, Fuminori Hyodo, Mayumi Yamato, Hideo Utsumi, Shigenobu Kanba, Redox and microglia in the pathophysiology of schizophrenia, Yakugaku Zasshi, 10.1248/yakushi.14-00235-4, 135, 5, 739-743, 2015.05, Altered antioxidant status has been implicated in schizophrenia. Microglia are major sources of free radicals such as superoxide in the brain, and play crucial roles in various brain diseases. Recent postmortem and imaging studies have in-dicated microglial activation in the brain of schizophrenia patients. Animal models that express some phenotypes of schizophrenia have revealed the underlying microglial pathology. In addition, minocycline, an antibiotic and the best known inhibitor of microglial activation, has therapeutic e‹cacy in schizophrenia. We have recently revealed that vari- ous antipsychotics directly affect microglia via proin‰ammatory reactions such as oxidative stress, by in vitro studies using rodent microglial cells. Based on these ˆndings, we have suggested that microglia are crucial players in the brain in schizophrenia, and modulating microglia may be a novel therapeutic target. In this review paper, we introduce our hypothesis based on the above evidence. The technique of in vivo molecular redox imaging is expected to be a powerful tool to clarify this hypothesis..
84. Motoki Watabe, Takahiro A. Kato, Alan R. Teo, Hideki Horikawa, Masaru Tateno, Kohei Hayakawa, Norihiro Shimokawa, Shigenobu Kanba, Relationship between trusting behaviors and psychometrics associated with social network and depression among young generation
A pilot study, PloS one, 10.1371/journal.pone.0120183, 10, 4, 2015.04, 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 realworld 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 (PHQ)-9. Consistent with previous research, male participants trusted partners more than female participants. Regression analysis revealed that LSNS-family (perceived support from family) for male participants, and item 8 of PHQ-9 (subjective agitation and/or retardation) for female participants were associated with participants' trusting behaviors. Consistent with claims by social scientists, our data suggest that, for males, support from family was negatively associated with cooperative behavior toward non-family members. Females with higher subjective agitation (and/or retardation) gave less money toward males and high attractive females, but not toward low attractive females in interpersonal relationships. We believe that our data indicate the possible impact of economic games in psychiatric research and clinical practice, and validation in clinical samples including modern-type depression and hikikomori should be investigated..
85. Alan R. Teo, Michael D. Fetters, Kyle Stufflebam, Masaru Tateno, Yatan Balhara, Tae Young Choi, Shigenobu Kanba, Carol A. Mathews, Takahiro A. Kato, Identification of the hikikomori syndrome of social withdrawal
Psychosocial features and treatment preferences in four countries, International Journal of Social Psychiatry, 10.1177/0020764014535758, 61, 1, 64-72, 2015.03, Background: Hikikomori, a form of social withdrawal first reported in Japan, may exist globally but cross-national studies of cases of hikikomori are lacking. Aims: To identify individuals with hikikomori in multiple countries and describe features of the condition. Method: Participants were recruited from sites in India, Japan, Korea and the United States. Hikikomori was defined as a 6-month or longer period of spending almost all time at home and avoiding social situations and social relationships, associated with significant distress/impairment. Additional measures included the University of California, Los Angeles (UCLA) Loneliness Scale, Lubben Social Network Scale (LSNS-6), Sheehan Disability Scale (SDS) and modified Cornell Treatment Preferences Index. Results: A total of 36 participants with hikikomori were identified, with cases detected in all four countries. These individuals had high levels of loneliness (UCLA Loneliness Scale M = 55.4, SD = 10.5), limited social networks (LSNS-6 M = 9.7, SD = 5.5) and moderate functional impairment (SDS M = 16.5, SD = 7.9). Of them 28 (78%) desired treatment for their social withdrawal, with a significantly higher preference for psychotherapy over pharmacotherapy, in-person over telepsychiatry treatment and mental health specialists over primary care providers. Across countries, participants with hikikomori had similar generally treatment preferences and psychosocial features. Conclusion: Hikikomori exists cross-nationally and can be assessed with a standardized assessment tool. Individuals with hikikomori have substantial psychosocial impairment and disability, and some may desire treatment..
86. Alan R. Teo, Takahiro A. Kato, The prevalence and correlates of severe social withdrawal in Hong Kong, International Journal of Social Psychiatry, 10.1177/0020764014554923, 61, 1, 102, 2015.03.
87. S. Kano, M. Yuan, R. A. Cardarelli, G. Maegawa, N. Higurashi, M. Gaval-Cruz, A. M. Wilson, C. Tristan, M. A. Kondo, Y. Chen, M. Koga, C. Obie, K. Ishizuka, S. Seshadri, R. Srivastava, T. A. Kato, Y. Horiuchi, T. W. Sedlak, Y. Lee, J. L. Rapoport, S. Hirose, H. Okano, D. Valle, P. O’Donnell, A. Sawa, M. Kai, Clinical utility of neuronal cells directly converted from fibroblasts of patients for neuropsychiatric disorders
Studies of lysosomal storage diseases and channelopathy, Current Molecular Medicine, 10.2174/1566524015666150303110300, 15, 2, 138-145, 2015.03, Methodologies for generating functional neuronal cells directly from human fibroblasts [induced neuronal (iN) cells] have been recently developed, but the research so far has only focused on technical refinements or recapitulation of known pathological phenotypes. A critical question is whether this novel technology will contribute to elucidation of novel disease mechanisms or evaluation of therapeutic strategies. Here we have addressed this question by studying Tay-Sachs disease, a representative lysosomal storage disease, and Dravet syndrome, a form of severe myoclonic epilepsy in infancy, using human iN cells with feature of immature postmitotic glutamatergic neuronal cells. In Tay-Sachs disease, we have successfully characterized canonical neuronal pathology, massive accumulation of GM2 ganglioside, and demonstrated the suitability of this novel cell culture for future drug screening. In Dravet syndrome, we have identified a novel functional phenotype that was not suggested by studies of classical mouse models and human autopsied brains. Taken together, the present study demonstrates that human iN cells are useful for translational neuroscience research to explore novel disease mechanisms and evaluate therapeutic compounds. In the future, research using human iN cells with well-characterized genomic landscape can be integrated into multidisciplinary patient-oriented research on neuropsychiatric disorders to address novel disease mechanisms and evaluate therapeutic strategies..
88. Yoshito Mizoguchi, Takahiro A. Kato, Hideki Horikawa, Akira Monji, Microglial intracellular Ca2+ signaling as a target of antipsychotic actions for the treatment of schizophrenia, Frontiers in Cellular Neuroscience, 10.3389/fncel.2014.00370, 8, November, 1-5, 2014.11, 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 Ca2+ 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 Ca2+ signaling underlies the pathophysiology of schizophrenia, while it remains unclear how typical or atypical antipsychotics affect intracellular Ca2+ 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 Ca2+ signaling and reinforces the importance of the ER of microglial cells as a target of antipsychotics for the treatment of schizophrenia..
89. Kazuhiko Yamamura, Shiori Kato, Takahiro A. Kato, Yoshito Mizoguchi, Akira Monji, Shigenobu Kanba, Masutaka Furue, Satoshi Takeuchi, Anti-allergic mechanisms of Japanese herbal medicine, yokukansan on mast cells, Journal of Dermatology, 10.1111/1346-8138.12578, 41, 9, 808-814, 2014.09, We previously reported that the addition of orally administered yokukansan (YKS), a traditional Japanese herbal medicine, to the standard regimen using histamine H1-receptor inhibitors was effective in controlling refractory chronic urticaria, but the mechanism remained unknown. YKS has also been reported to be effective on inhibiting the development of atopic dermatitis-like skin lesions in NC/Nga mice. As known, the release of various chemical mediators including histamine from degranulated mast cells is strongly related to the mechanism of these diseases. Thus the purpose of this study was to examine the mechanisms behind the medicinal effects of YKS on mast cells using an in vitro system and rat basophil leukemia (RBL-2H3) cells. The degree of degranulation was measured by β-hexosaminidase secretion assay and intracellular calcium influx assay. ELISA for cytokines (TNF-α and IL-4) was also conducted using cell culture media. Furthermore, we investigated the effects of YKS on the expression of adhesion molecules (ICAM-1, VCAM-1, E-selectin) and cytokine production (IL-8) in human dermal microvascular endothelial cells using gene-transcriptional- and immunohisotoligical analysis. We found that YKS inhibited secretion of β-hexosaminidase, intracellular calcium increase, production of TNF-α and ICAM-1 expression, and that several YKS ingredients may be the key effectors. In conclusion, YKS may suppress several mast cell functions such as degranulation and calcium increase that eventually inhibits the release of proinflammatory cytokines. Furthermore, YKS suppresses ICAM-1 expression on human microvascular endothelial cells. These findings may promote our understanding of the beneficial effects of YKS on mast cell-associated allergic diseases..
90. Y. Suzuki, T. A. Kato, R. Sato, D. Fujisawa, K. Aoyama-Uehara, N. Hashimoto, N. Yonemoto, M. Fukasawa, K. Otsuka, Effectiveness of brief suicide management training programme for medical residents in Japan
A cluster randomized controlled trial, Epidemiology and Psychiatric Sciences, 10.1017/S2045796013000334, 23, 2, 167-176, 2014.06, 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 examined immediately after the intervention in the adjusted model, with a mean difference in score of 9.98 (95% confidence interval: 4.39-15.56; p = 0.001). Conclusions. The structured programme was not proven to improve competency in suicide management when measured by the SIRI-1 score. Further elaboration of the programme and valid measurement of its outcome would be needed to show the program's effectiveness..
91. Yoshito Mizoguchi, Takahiro A. Kato, Yoshihiro Seki, Masahiro Ohgidani, Noriaki Sagata, Hideki Horikawa, Yusuke Yamauchi, Mina Sato-Kasai, Kohei Hayakawa, Ryuji Inoue, Shigenobu Kanba, Akira Monji, Brain-derived neurotrophic factor (BDNF) induces sustained intracellular Ca2+ elevation through the up-regulation of surface transient receptor potential 3 (TRPC3) channels in rodent microglia, Journal of Biological Chemistry, 10.1074/jbc.M114.555334, 289, 26, 18549-18555, 2014.06, Microglia are immune cells that release factors, including proinflammatory cytokines, nitric oxide (NO), and neurotrophins, following activation after disturbance in the brain. Elevation of intracellular Ca2+ concentration ([Ca2+]i) is important for microglial functions such as the release of cytokines and NO from activated microglia. There is increasing evidence suggesting that pathophysiology of neuropsychiatric disorders is related to the inflammatory responses mediated by microglia. Brain-derived neurotrophic factor (BDNF) is a neurotrophin well known for its roles in the activation of microglia as well as in pathophysiology and/or treatment of neuropsychiatric disorders. In this study, we sought to examine the underlying mechanism of BDNF-induced sustained increase in [Ca2+]j in rodent microglial cells. We observed that canonical transient receptor potential 3 (TRPC3) channels contribute to the maintenance of BDNF-induced sustained intracellular Ca2+ elevation. Immunocytochemical technique and flow cytometry also revealed that BDNF rapidly up-regulated the surface expression of TRPC3 channels in rodent microglial cells. In addition, pretreatment with BDNF suppressed the production of NO induced by tumor necrosis factor α (TNFα), which was prevented by co-adiministration of a selective TRPC3 inhibitor. These suggest that BDNF induces sustained intracellular Ca2+ elevation through the up-regulation of surface TRPC3 channels and TRPC3 channels could be important for the BDNF-induced suppression of the NO production in activated microglia. We show that TRPC3 channels could also play important roles in microglial functions, which might be important for the regulation of inflammatory responses and may also be involved in the pathophysiology and/or the treatment of neuropsychiatric disorders..
92. Masahiro Ohgidani, Takahiro A. Kato, Daiki Setoyama, Noriaki Sagata, Ryota Hashimoto, Kazue Shigenobu, Tetsuhiko Yoshida, Kohei Hayakawa, Norihiro Shimokawa, Daisuke Miura, Hideo Utsumi, Shigenobu Kanba, Direct induction of ramified microglia-like cells from human monocytes
Dynamic microglial dysfunction in Nasu-Hakola disease, Scientific reports, 10.1038/srep04957, 4, 2014.05, Microglia have been implicated in various neurological and psychiatric disorders in rodent and human postmortem studies. However, the dynamic actions of microglia in the living human brain have not been clarified due to a lack of studies dealing with in situ microglia. Herein, we present a novel technique for developing induced microglia-like (iMG) cells from human peripheral blood cells. An optimized cocktail of cytokines, GM-CSF and IL-34, converted human monocytes into iMG cells within 14 days. The iMG cells have microglial characterizations; expressing markers, forming a ramified morphology, and phagocytic activity with various cytokine releases. To confirm clinical utilities, we developed iMG cells from a patient of Nasu-Hakola disease (NHD), which is suggested to be directly caused by microglial dysfunction, and observed that these cells from NHD express delayed but stronger inflammatory responses compared with those from the healthy control. Altogether, the iMG-technique promises to elucidate unresolved aspects of human microglia in various brain disorders..
93. Kohei Hayakawa, Takahiro A. Kato, Masaomi Kohjiro, Akira Monji, Shigenobu Kanba, Minocycline, a microglial inhibitor, diminishes terminal patients' delirium?, American Journal of Geriatric Psychiatry, 10.1016/j.jagp.2013.11.003, 22, 3, 314-315, 2014.03.
94. Shigenobu Kanba, Takahiro Kato, Microglial hypothesis of schizophrenia, Japanese Journal of Neuropsychopharmacology, 34, 1, 11-13, 2014.02, 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..
95. , Kitty Farooq, Gregory J. Lydall, Amit Malik, David M. Ndetei, Dinesh Bhugra, Yonas Baheretibeb Alemu, Sammy Ohene, Muthoni Mathai, Benson Gakinya, Richard Uwakwa, Femi Olugbile, Kiyeti Hauli, Joyce Mugaza, Gad Kilonzo, Seggane Musisi, Samuel Maling, Paul Ravi, Rubens Luis Folchini Fernandes, Luiz Antonio Nogueira-Martins, Jair de Jesus Mari, Sergio Baldassin, Nilson Rodrigues da Silva, Karen Saperson, Martina Rojnic Kuzman, Petra Lovrec, Mia Smoljan, Benjamin Vicente, Leonardo Rosel, Alexander Nawka, Lucie Nawkova, Boris Dvoracek, Olivier Andlauer, Emmanuel Haffen, Daniel Sechter, William Guicherd, Bernard Bonin, Iris Tatjana Calliess, Volkhard Fischer, Anke Mittelstädt, Vanessa Wong, P. S.V.N. Sharma, Sumit Deora, Suma Udupa, A. Rasoul Yasiri, Basil Al-Chalabi, Ali Al-Hamzawi, Sirwan Ali, Akeel Al-Sabbagh, Takahiro A. Kato, Shigenobu Kanba, Why medical students choose psychiatry - A 20 country cross-sectional survey, BMC Medical Education, 10.1186/1472-6920-14-12, 14, 1, 2014.01, Background: Recruitment to psychiatry is insufficient to meet projected mental health service needs world-wide. We report on the career plans of final year medical students from 20 countries, investigating factors identified from the literature which influence psychiatric career choice. Methods. Cross sectional electronic or paper survey. Subjects were final year medical students at 46 medical schools in participating countries. We assessed students' career intentions, motivations, medical school teaching and exposure to psychiatry. We assessed students' attitudes and personality factors. The main outcome measure was likelihood of specializing in psychiatry. Multilevel logistic regression was used to examine the joint effect of factors upon the main outcome. Results: 2198 of 9135 (24%) of students responded (range 4 to 91%) across the countries. Internationally 4.5% of students definitely considered psychiatry as a career (range 1 to 12%). 19% of students (range 0 to 33%) were "quite likely", and 25% were "definitely not" considering psychiatry. Female gender, experience of mental/physical illness, media portrayal of doctors, and positive attitudes to psychiatry, but not personality factors, were associated with choosing psychiatry. Quality of psychiatric placement (correlation coefficient = 0.22, p < 0.001) and number of placements (correlation coefficient =0.21, p < 0.001) were associated with higher ATP scores. During medical school, experience of psychiatric enrichment activities (special studies modules and university psychiatry clubs), experience of acutely unwell patients and perceived clinical responsibility were all associated with choice of psychiatry. Multilevel logistic regression revealed six factors associated with students choosing psychiatry: importance of own vocation, odds ratio (OR) 3.01, 95% CI 1.61 to 5.91, p < 0.001); interest in psychiatry before medical school, OR 10.8 (5.38 to 21.8, p < 0.001); undertaking a psychiatry special study module, OR 1.45 (1.05 to 2.01, p = 0.03) or elective OR 4.28 (2.87- 6.38, p < 0.001); membership of a university psychiatry club, OR 3.25 (2.87 to 6.38, p < 0.001); and exposure to didactic teaching, OR 0.54 (0.40 to 0.72, p < 0.001). Conclusions: We report factors relevant to medical student selection and psychiatry teaching which affect career choice. Addressing these factors may improve recruitment to psychiatry internationally..
96. Kitty Farooq, Gregory J Lydall, Amit Malik, David M Ndetei, ISOSCCIP Group, Dinesh Bhugra, Yonas Baheretibeb Alemu, Sammy Ohene, Muthoni Mathai, Benson Gakinya, Richard Uwakwa, Femi Olugbile, Kiyeti Hauli, Joyce Mugaza, Gad Kilonzo, Seggane Musisi, Samuel Maling, Paul Ravi, Rubens Luis Folchini Fernandes, Luiz Antonio Nogueira-Martins, Jair de Jesus Mari, Sergio Baldassin, Nilson Rodrigues da Silva, Karen Saperson, Martina Rojnic Kuzman, Petra Lovrec, Mia Smoljan, Benjamin Vicente, Leonardo Rosel, Alexander Nawka, Lucie Nawkova, Boris Dvoracek, Olivier Andlauer, Emmanuel Haffen, Daniel Sechter, William Guicherd, Bernard Bonin, Iris Tatjana Calliess, Volkhard Fischer, Anke Mittelstädt, Vanessa Wong, P. S.V.N. Sharma, Sumit Deora, Suma Udupa, A-Rasoul Yasiri, Basil Al-Chalabi, Ali Al-Hamzawi, Sirwan Ali, Akeel Al-Sabbagh, Eyal Dahan, Karin Schlossberg, Silvia Ferrari, Corinna Reggianini, Giorgio Mattei, Luca Pingani, Takahiro A. Kato, Shigenobu Kanba, Masaru Tateno, Soraya Seedat, Sharain Suliman, Wolfgang Gerke, Ulrich Schnyder, François Ferrero, Guido Bondolf, Neel Halder, Christiana Hadjidemetriou, Rachel Pearson, Why medical students choose psychiatry - A 20 country cross-sectional survey, BMC Medical Education, 10.1186/1472-6920-14-12, 14, 1, 2014.01, Background: Recruitment to psychiatry is insufficient to meet projected mental health service needs world-wide. We report on the career plans of final year medical students from 20 countries, investigating factors identified from the literature which influence psychiatric career choice. Methods. Cross sectional electronic or paper survey. Subjects were final year medical students at 46 medical schools in participating countries. We assessed students' career intentions, motivations, medical school teaching and exposure to psychiatry. We assessed students' attitudes and personality factors. The main outcome measure was likelihood of specializing in psychiatry. Multilevel logistic regression was used to examine the joint effect of factors upon the main outcome. Results: 2198 of 9135 (24%) of students responded (range 4 to 91%) across the countries. Internationally 4.5% of students definitely considered psychiatry as a career (range 1 to 12%). 19% of students (range 0 to 33%) were "quite likely", and 25% were "definitely not" considering psychiatry. Female gender, experience of mental/physical illness, media portrayal of doctors, and positive attitudes to psychiatry, but not personality factors, were associated with choosing psychiatry. Quality of psychiatric placement (correlation coefficient = 0.22, p <
0.001) and number of placements (correlation coefficient =0.21, p <
0.001) were associated with higher ATP scores. During medical school, experience of psychiatric enrichment activities (special studies modules and university psychiatry clubs), experience of acutely unwell patients and perceived clinical responsibility were all associated with choice of psychiatry. Multilevel logistic regression revealed six factors associated with students choosing psychiatry: importance of own vocation, odds ratio (OR) 3.01, 95% CI 1.61 to 5.91, p <
0.001)
interest in psychiatry before medical school, OR 10.8 (5.38 to 21.8, p <
0.001)
undertaking a psychiatry special study module, OR 1.45 (1.05 to 2.01, p = 0.03) or elective OR 4.28 (2.87- 6.38, p <
0.001)
membership of a university psychiatry club, OR 3.25 (2.87 to 6.38, p <
0.001)
and exposure to didactic teaching, OR 0.54 (0.40 to 0.72, p <
0.001). Conclusions: We report factors relevant to medical student selection and psychiatry teaching which affect career choice. Addressing these factors may improve recruitment to psychiatry internationally. © 2014 Farooq et al.
licensee BioMed Central Ltd..
97. Yoshihiro Seki, Takahiro A. Kato, Akira Monji, Yoshito Mizoguchi, Hideki Horikawa, Mina Sato-Kasai, Daigo Yoshiga, Shigenobu Kanba, Pretreatment of aripiprazole and minocycline, but not haloperidol, suppresses oligodendrocyte damage from interferon-γ-stimulated microglia in co-culture model, Schizophrenia research, 10.1016/j.schres.2013.09.011, 151, 1-3, 20-28, 2013.12, 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 suppressed apoptosis of oligodendrocytes in the co-culture model with interferon-γ (IFN-γ)-activated microglia, while haloperidol, a traditional antipsychotic drug, did not. Aripiprazole and minocycline inhibited the production of tumor necrosis factor-alpha (TNF-α) from IFN-γ-activated microglia. Moreover, aripiprazole and minocycline attenuated the phosphorylation of signal transducer and activator of transcription 1 (STAT1) in microglia. Overall, our results suggest that aripiprazole and minocycline may have antipsychotic effects through reducing oligodendrocyte damage caused by microglial activation. These results put forward a novel therapeutic hypothesis in schizophrenia research. Future in vivo studies to confirm the present results should be performed..
98. Seki Y, Kato TA, Monji A, Mizoguchi Y, Horikawa H, Sato-Kasai M, Yoshiga D, Kanba S, Pretreatment of aripiprazole and minocycline, but not haloperidol, suppresses oligodendrocyte damage from interferon-γ-stimulated microglia in co-culture model., Schizophrenia research, 10.1016/j.schres.2013.09.011, 151, 1-3, 20-28, 2013.12.
99. Daisuke Fujisawa, Yuriko Suzuki, Takahiro A. Kato, Naoki Hashimoto, Ryoko Sato, Kumi Aoyama-Uehara, Maiko Fukasawa, Masayuki Tomita, Koichiro Watanabe, Haruo Kashima, Kotaro Otsuka, Suicide intervention skills among Japanese medical residents, Academic Psychiatry, 10.1176/appi.ap.10110154, 37, 6, 402-407, 2013.11, Objectives: Patient suicide is a tragic occurrence, and it can be a demoralizing experience for medical residents. Few studies, however, have assessed suicide management skills among these front-line healthcare professionals. This study evaluated the selfassessed competence and confidence of medical residents with regard to the management of potentially suicidal patients and assessed the correlation with the residents' background characteristics. Method: The authors conducted a multicenter, cross-sectional survey of 114 medical residents in Japan, using a modified version of the Suicide Intervention Response Inventory (SIRI22), the Medical Outcomes Study 8-Item Short-Form Health Survey (SF28), and a 5-point Likert scale to assess confidence in suicide management. Results: A majority (89.5%) of the residents rated their confidence in managing suicidal patients as Not At All Confident or Rather Not Confident, although most were close to completing their psychiatric rotation. Results on the SIRI22 suggested intermediate competence in managing suicidal behavior, as compared with that of other healthcare professionals. Competence as indicated by the SIRI22 score was weakly and negatively correlated with the score for self-perceived Vitality on the SF28 scale. Conclusion: Insufficient skills and lack of confidence in the management of suicidal patients was observed in this sample of Japanese medical residents, thus highlighting the need for improved suicide-management programs for junior medical residents in Japanese hospitals..
100. Daisuke Fujisawa, Yuriko Suzuki, Takahiro A. Kato, Naoki Hashimoto, Ryoko Sato, Kumi Aoyama-Uehara, Maiko Fukasawa, Masayuki Tomita, Koichiro Watanabe, Haruo Kashima, Kotaro Otsuka, Suicide Intervention Skills Among Japanese Medical Residents, ACADEMIC PSYCHIATRY, 10.1176/appi.ap.10110154, 37, 6, 402-407, 2013.11, Objectives: Patient suicide is a tragic occurrence, and it can be a demoralizing experience for medical residents. Few studies, however, have assessed suicide management skills among these front-line healthcare professionals. This study evaluated the self-assessed competence and confidence of medical residents with regard to the management of potentially suicidal patients and assessed the correlation with the residents' background characteristics.
Method: The authors conducted a multicenter, cross-sectional survey of 114 medical residents in Japan, using a modified version of the Suicide Intervention Response Inventory (SIRI-2), the Medical Outcomes Study 8-Item Short-Form Health Survey (SF-8), and a 5-point Likert scale to assess confidence in suicide management.
Results: A majority (89.5%) of the residents rated their confidence in managing suicidal patients as Not At All Confident or Rather Not Confident, although most were close to completing their psychiatric rotation. Results on the SIRI-2 suggested intermediate competence in managing suicidal behavior, as compared with that of other healthcare professionals. Competence as indicated by the SIRI-2 score was weakly and negatively correlated with the score for self-perceived Vitality on the SF-8 scale.
Conclusion: Insufficient skills and lack of confidence in the management of suicidal patients was observed in this sample of Japanese medical residents, thus highlighting the need for improved suicide-management programs for junior medical residents in Japanese hospitals..
101. Kato TA, Balhara YPS, Chawla JM, Tateno M, Kanba S, Undergraduate medical students' attitudes toward psychiatry: an international cross-sectional survey between India and Japan., International Review of Psychiatry, 25, 4, 378-384, 2013.09.
102. Isomura S, Monji A, Sasaki K, Baba S, Onitsuka T, Ohara T, Mizoguchi Y, Kato TA, Horikawa H, Seki Y, Kanba S:, FTD with catatonia-like signs that temporarily resolved with zolpidem, Neurology: Clinical Practice, 10.1212/CPJ.0b013e318296f263, 3, 4, 354-357, 2013.08.
103. Takahiro A. Kato, Yatan Pal Singh Balhara, Jatinder Mohan Chawla, Masaru Tateno, Shigenobu Kanba, Undergraduate medical students' attitudes towards psychiatry
An international cross-sectional survey between India and Japan, International Review of Psychiatry, 10.3109/09540261.2013.812959, 25, 4, 378-384, 2013.08, Undergraduate psychiatric education has an important role in developing psychiatric knowledge, decreasing stigma towards mental illness, and promoting psychiatry as a career choice. The attitudes and beliefs of medical students towards psychiatry have not been well understood, especially in non-western countries. To clarify this aspect, we have conducted a cross-sectional study between India and Japan. This study, conducted at two centres, one each in India and Japan, used a semi-structured questionnaire to evaluate the attitudes and beliefs of third-year medical students towards mental illness and psychiatry; such as emotions experienced dealing with psychiatric patients, aetiology and treatment of psychiatric disorders, and psychiatry as a career choice. A total of 79 medical students from India and 77 from Japan participated in the present study. Significant differences were observed in the emotions experienced by the medical students while dealing with psychiatric patients. Most medical students (> 90%) from both study sites favoured psychiatrists for treatment of psychiatric illness. Psychiatry as a carrier choice was significantly related to the nationality of the medical students. The findings of the current study provide insight in to the attitudes of third-year medical students from India and Japan towards psychiatric patients..
104. Motoki Watabe, Takahiro A. Kato, Sho Tsuboi, Katsuhiko Ishikawa, Kazuhide Hashiya, Akira Monji, Hideo Utsumi, Shigenobu Kanba, Minocycline, a microglial inhibitor, reduces 'honey trap' risk in human economic exchange, Scientific reports, 10.1038/srep01685, 3, 2013.04, Recently, minocycline, a tetracycline antibiotic, has been reported to improve symptoms of psychiatric disorders and to facilitate sober decision-making in healthy human subjects. Here we show that minocycline also reduces the risk of the 'honey trap' during an economic exchange. Males tend to cooperate with physically attractive females without careful evaluation of their trustworthiness, resulting in betrayal by the female. In this experiment, healthy male participants made risky choices (whether or not to trust female partners, identified only by photograph, who had decided in advance to exploit the male participants). The results show that trusting behaviour in male participants significantly increased in relation to the perceived attractiveness of the female partner, but that attractiveness did not impact trusting behaviour in the minocycline group. Animal studies have shown that minocycline inhibits microglial activities. Therefore, this minocycline effect may shed new light on the unknown roles microglia play in human mental activities..
105. Akira Monji, Takahiro A. Kato, Yoshito Mizoguchi, Hideki Horikawa, Yoshihiro Seki, Mina Kasai, Yusuke Yamauchi, Shigeto Yamada, Shigenobu Kanba, Neuroinflammation in schizophrenia especially focused on the role of microglia, Progress in Neuro-Psychopharmacology and Biological Psychiatry, 10.1016/j.pnpbp.2011.12.002, 42, 115-121, 2013.04, 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 through the inhibition of microglial activation may shed new light on the therapeutic strategy of schizophrenia..
106. Motoki Watabe, Takahiro A. Kato, Sho Tsuboi, Katsuhiko Ishikawa, Kazuhide Hashiya, Akira Monji, Hideo Utsumi, Shigenobu Kanba, Minocycline, a microglial inhibitor, reduces 'honey trap' risk in human economic exchange, Scientific Reports, 10.1038/srep01685, 3, 1685, 2013.04, Recently, minocycline, a tetracycline antibiotic, has been reported to improve symptoms of psychiatric disorders and to facilitate sober decision-making in healthy human subjects. Here we show that minocycline also reduces the risk of the 'honey trap' during an economic exchange. Males tend to cooperate with physically attractive females without careful evaluation of their trustworthiness, resulting in betrayal by the female. In this experiment, healthy male participants made risky choices (whether or not to trust female partners, identified only by photograph, who had decided in advance to exploit the male participants). The results show that trusting behaviour in male participants significantly increased in relation to the perceived attractiveness of the female partner, but that attractiveness did not impact trusting behaviour in the minocycline group. Animal studies have shown that minocycline inhibits microglial activities. Therefore, this minocycline effect may shed new light on the unknown roles microglia play in human mental activities..
107. Akira Monji, Takahiro A. Kato, Yoshito Mizoguchi, Hideki Horikawa, Yoshihiro Seki, Mina Kasai, Yusuke Yamauchi, Shigeto Yamada, Shigenobu Kanba, Neuroinflammation in schizophrenia especially focused on the role of microglia, PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY, 10.1016/j.pnpbp.2011.12.002, 42, 115-121, 2013.04, 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 through the inhibition of microglial activation may shed new light on the therapeutic strategy of schizophrenia. (C) 2012 Elsevier Inc. All rights reserved..
108. Umene-Nakano Wakako, Kato A. Takahiro, Kikuchi S, Tateno M, Fujisawa D, Hoshuyama T, Nakamura J, Nationwide Survey of Work Environment, Work-Life Balance and Burnout among Psychiatrists in Japan., PLoS ONE, 10.1371/journal.pone.0055189, 8, 2, e55189, 2013.02.
109. Masaru Tateno, Tae W. Park, Takahiro A. Kato, Wakako Umene-Nakano, Toshikazu Saito, Hikikomori as a possible clinical term in psychiatry
a questionnaire survey, BMC Psychiatry, 10.1186/1471-244X-12-169, 12, 2012.10, Background: The word hikikomori, the abnormal avoidance of social contact, has become increasingly well-known. However, a definition of this phenomenon has not been discussed thoroughly. The aim of this study is to gain a better understanding of the perception of hikikomori amongst health-related students and professionals and to explore possible psychiatric conditions underlying hikikomori.Methods: A total of 1,038 subjects were requested to complete a questionnaire regarding hikikomori phenomenon.Results: While some differences in the perception of hikikomori do exist, all subjects tended to disagree with the statement, " hikikomori is NOT a disorder" . Regarding the underlying psychiatric disorders of hikikomori, approximately 30% of psychiatrists chose schizophrenia as the most applicable ICD-10 diagnosis for hikikomori, whereas 50% of pediatricians chose neurotic or stress-related disorders.Conclusions: An argument still exists regarding the relationship between hikikomori and psychiatric disorders. We propose that the term hikikomori could be used to describe severe social withdrawal in the setting of a number of psychiatric disorders..
110. Masaru Tateno, Tae Woo Park, Takahiro A. Kato, Wakako Umene-Nakano, Toshikazu Saito, Hikikomori as a possible clinical term in psychiatry: a questionnaire survey, BMC PSYCHIATRY, 10.1186/1471-244X-12-169, 12, 169, 2012.10, Background: The word hikikomori, the abnormal avoidance of social contact, has become increasingly well-known. However, a definition of this phenomenon has not been discussed thoroughly. The aim of this study is to gain a better understanding of the perception of hikikomori amongst health-related students and professionals and to explore possible psychiatric conditions underlying hikikomori.
Methods: A total of 1,038 subjects were requested to complete a questionnaire regarding hikikomori phenomenon.
Results: While some differences in the perception of hikikomori do exist, all subjects tended to disagree with the statement, "hikikomori is NOT a disorder". Regarding the underlying psychiatric disorders of hikikomori, approximately 30% of psychiatrists chose schizophrenia as the most applicable ICD-10 diagnosis for hikikomori, whereas 50% of pediatricians chose neurotic or stress-related disorders.
Conclusions: An argument still exists regarding the relationship between hikikomori and psychiatric disorders. We propose that the term hikikomori could be used to describe severe social withdrawal in the setting of a number of psychiatric disorders..
111. Takahiro A. Kato, Masaru Tateno, Naotaka Shinfuku, Daisuke Fujisawa, Alan R. Teo, Norman Sartorius, Tsuyoshi Akiyama, Tetsuya Ishida, Tae Young Choi, Yatan Pal Singh Balhara, Ryohei Matsumoto, Umene Nakano Wakako, Yota Fujimura, Anne Wand, Jane Pei Chen Chang, Rita Yuan Feng Chang, Behrang Shadloo, Helal Uddin Ahmed, Tiraya Lerthattasilp, Shigenobu Kanba, Does the 'hikikomori' syndrome of social withdrawal exist outside Japan? A preliminary international investigation, Social Psychiatry and Psychiatric Epidemiology, 10.1007/s00127-011-0411-7, 47, 7, 1061-1075, 2012.07, Purpose: To explore whether the 'hikikomori' syndrome (social withdrawal) described in Japan exists in other countries, and if so, how patients with the syndrome are diagnosed and treated. Methods: Two hikikomori case vignettes were sent to psychiatrists in Australia, Bangladesh, India, Iran, Japan, Korea, Taiwan, Thailand and the USA. Participants rated the syndrome's prevalence in their country, etiology, diagnosis, suicide risk, and treatment. Results: Out of 247 responses to the questionnaire (123 from Japan and 124 from other countries), 239 were enrolled in the analysis. Respondents' felt the hikikomori syndrome is seen in all countries examined and especially in urban areas. Biopsychosocial, cultural, and environmental factors were all listed as probable causes of hikikomori, and differences among countries were not significant. Japanese psychiatrists suggested treatment in outpatient wards and some did not think that psychiatric treatment is necessary. Psychiatrists in other countries opted for more active treatment such as hospitalization. Conclusions: Patients with the hikikomori syndrome are perceived as occurring across a variety of cultures by psychiatrists in multiple countries. Our results provide a rational basis for study of the existence and epidemiology of hikikomori in clinical or community populations in international settings..
112. Takahiro A. Kato, Motoki Watabe, Sho Tsuboi, Katsuhiko Ishikawa, Kazuhide Hashiya, Akira Monji, Hideo Utsumi, Shigenobu Kanba, Minocycline modulates human social decision-making
Possible impact of microglia on personality-oriented social behaviors, PloS one, 10.1371/journal.pone.0040461, 7, 7, 2012.07, Background: Microglia, one of the glial cells, play important roles in various brain pathologies including psychiatric disorders. In addition, microglia have recently been proved to monitor synaptic reactions via direct-touching even in normal brain. Human microglia may modulate various social/mental functions, while microglial social/mental roles remain unresolved especially in healthy humans. There is no known drug with the specific effect of modulating microglia. Therefore, using minocycline, a tetracycline antibiotic and the most famous microglial inhibitor, is one of the best alternative approaches to clarify microglial functions on human social/mental activities. Methodology/Principal Findings: We conducted a double-blind randomized trial of trust game, a monetary decision-making experiment, with ninety-nine human adult males who decided how much to trust an anonymous partner after a four-day administration of minocycline. Our previous pilot trial indicated a positive effect of minocycline, while the underlying mechanisms were not clarified. Therefore, in this trial with larger samples, we additionally measured the effects of anxiety and personality. The monetary score in trust game was significantly lower in the minocycline group. Interestingly, participants' ways of decision-making were significantly shifted; cooperativeness, one component of personality, proved to be the main modulating factor of decision-making in the placebo group, on the other hand, the minocycline group was mainly modulated by state anxiety and trustworthiness. Conclusions/Significance: Our results suggest that minocycline led to more situation-oriented decision-making, possibly by suppressing the effects of personality traits, and furthermore that personality and social behaviors might be modulated by microglia. Early-life events may activate human microglia, establish a certain neuro-synaptic connection, and this formation may determine each human's personality and personality- oriented social behaviors in later life. To explore these mechanisms, further translational research is needed..
113. Takahiro A. Kato, Masaru Tateno, Naotaka Shinfuku, Daisuke Fujisawa, Alan R. Teo, Norman Sartorius, Tsuyoshi Akiyama, Tetsuya Ishida, Tae Young Choi, Yatan Pal Singh Balhara, Ryohei Matsumoto, Wakako Umene-Nakano, Yota Fujimura, Anne Wand, Jane Pei-Chen Chang, Rita Yuan-Feng Chang, Behrang Shadloo, Helal Uddin Ahmed, Tiraya Lerthattasilp, Shigenobu Kanba, Does the 'hikikomori' syndrome of social withdrawal exist outside Japan? A preliminary international investigation, SOCIAL PSYCHIATRY AND PSYCHIATRIC EPIDEMIOLOGY, 10.1007/s00127-011-0411-7, 47, 7, 1061-1075, 2012.07, To explore whether the 'hikikomori' syndrome (social withdrawal) described in Japan exists in other countries, and if so, how patients with the syndrome are diagnosed and treated.
Two hikikomori case vignettes were sent to psychiatrists in Australia, Bangladesh, India, Iran, Japan, Korea, Taiwan, Thailand and the USA. Participants rated the syndrome's prevalence in their country, etiology, diagnosis, suicide risk, and treatment.
Out of 247 responses to the questionnaire (123 from Japan and 124 from other countries), 239 were enrolled in the analysis. Respondents' felt the hikikomori syndrome is seen in all countries examined and especially in urban areas. Biopsychosocial, cultural, and environmental factors were all listed as probable causes of hikikomori, and differences among countries were not significant. Japanese psychiatrists suggested treatment in outpatient wards and some did not think that psychiatric treatment is necessary. Psychiatrists in other countries opted for more active treatment such as hospitalization.
Patients with the hikikomori syndrome are perceived as occurring across a variety of cultures by psychiatrists in multiple countries. Our results provide a rational basis for study of the existence and epidemiology of hikikomori in clinical or community populations in international settings..
114. Takahiro A. Kato, Motoki Watabe, Sho Tsuboi, Katsuhiko Ishikawa, Kazuhide Hashiya, Akira Monji, Hideo Utsumi, Shigenobu Kanba, Minocycline Modulates Human Social Decision-Making: Possible Impact of Microglia on Personality-Oriented Social Behaviors, PLOS ONE, 10.1371/journal.pone.0040461, 7, 7, e40461, 2012.07, Background: Microglia, one of the glial cells, play important roles in various brain pathologies including psychiatric disorders. In addition, microglia have recently been proved to monitor synaptic reactions via direct-touching even in normal brain. Human microglia may modulate various social/mental functions, while microglial social/mental roles remain unresolved especially in healthy humans. There is no known drug with the specific effect of modulating microglia. Therefore, using minocycline, a tetracycline antibiotic and the most famous microglial inhibitor, is one of the best alternative approaches to clarify microglial functions on human social/mental activities.
Methodology/Principal Findings: We conducted a double-blind randomized trial of trust game, a monetary decision-making experiment, with ninety-nine human adult males who decided how much to trust an anonymous partner after a four-day administration of minocycline. Our previous pilot trial indicated a positive effect of minocycline, while the underlying mechanisms were not clarified. Therefore, in this trial with larger samples, we additionally measured the effects of anxiety and personality. The monetary score in trust game was significantly lower in the minocycline group. Interestingly, participants' ways of decision-making were significantly shifted; cooperativeness, one component of personality, proved to be the main modulating factor of decision-making in the placebo group, on the other hand, the minocycline group was mainly modulated by state anxiety and trustworthiness.
Conclusions/Significance: Our results suggest that minocycline led to more situation-oriented decision-making, possibly by suppressing the effects of personality traits, and furthermore that personality and social behaviors might be modulated by microglia. Early-life events may activate human microglia, establish a certain neuro-synaptic connection, and this formation may determine each human's personality and personality-oriented social behaviors in later life. To explore these mechanisms, further translational research is needed..
115. Motoki Watabe, Takahiro A. Kato, Akira Monji, Hideki Horikawa, Shigenobu Kanba, Does minocycline, an antibiotic with inhibitory effects on microglial activation, sharpen a sense of trust in social interaction?, Psychopharmacology, 10.1007/s00213-011-2509-8, 220, 3, 551-557, 2012.04, Rationale Minocycline has long been applied to various infectious diseases as a tetracycline antibiotic and recently has found new application in the treatment of brain diseases such as stroke and multiple sclerosis. In addition, minocy-cline has also been suggested as an effective drug for psychiatric diseases. These suggestions imply that minocy-cline may modulate our mental activities, while the underlying mechanism remains to be clarified. Objective To investigate how minocycline influences human mental activity, we experimentally examined how minocycline works on human social decision making in a double-blind randomized trial. Methods Forty-nine healthy volunteers were administered minocycline or placebo over four days, after which they played (1) a trust game, in which they decided how much to trust an anonymous partner, and (2) a dictator game, in which they decided how to divide resources between themselves and an anonymous partner. Results The minocycline group did not display increased trusting behavior or more altruistic resource allocation. In fact, the minocycline group displayed a slight reduction in trusting behavior. However, the minocycline group did show a strong positive correlation between the degree of risk taking in the trust game and in a separate evaluation of others' trustworthiness, whereas the placebo group showed no such correlation. Conclusions These results suggest that minocycline led to more rational decision-making strategies, possibly by increasing emotion regulation. Since minocycline is a well-known inhibitor of microglial activation, our findings may open a new optional pathway for treating mental states in which a component of rational decision making is impaired..
116. Motoki Watabe, Takahiro A. Kato, Akira Monji, Hideki Horikawa, Shigenobu Kanba, Does minocycline, an antibiotic with inhibitory effects on microglial activation, sharpen a sense of trust in social interaction?, PSYCHOPHARMACOLOGY, 10.1007/s00213-011-2509-8, 220, 3, 551-557, 2012.04, Minocycline has long been applied to various infectious diseases as a tetracycline antibiotic and recently has found new application in the treatment of brain diseases such as stroke and multiple sclerosis. In addition, minocycline has also been suggested as an effective drug for psychiatric diseases. These suggestions imply that minocycline may modulate our mental activities, while the underlying mechanism remains to be clarified.
To investigate how minocycline influences human mental activity, we experimentally examined how minocycline works on human social decision making in a double-blind randomized trial.
Forty-nine healthy volunteers were administered minocycline or placebo over four days, after which they played (1) a trust game, in which they decided how much to trust an anonymous partner, and (2) a dictator game, in which they decided how to divide resources between themselves and an anonymous partner.
The minocycline group did not display increased trusting behavior or more altruistic resource allocation. In fact, the minocycline group displayed a slight reduction in trusting behavior. However, the minocycline group did show a strong positive correlation between the degree of risk taking in the trust game and in a separate evaluation of others' trustworthiness, whereas the placebo group showed no such correlation.
These results suggest that minocycline led to more rational decision-making strategies, possibly by increasing emotion regulation. Since minocycline is a well-known inhibitor of microglial activation, our findings may open a new optional pathway for treating mental states in which a component of rational decision making is impaired..
117. Takahiro A. Kato, Naotaka Shinfuku, Daisuke Fujisawa, Masaru Tateno, Tetsuya Ishida, Tsuyoshi Akiyama, Norman Sartorius, Alan R. Teo, Tae Young Choi, Anne P.F. Wand, Yatan Pal Singh Balhara, Jane Pei Chen Chang, Rita Yuan Feng Chang, Behrang Shadloo, Helal Uddin Ahmed, Tiraya Lerthattasilp, Wakako Umene-Nakano, Hideki Horikawa, Ryohei Matsumoto, Hironori Kuga, Masuo Tanaka, Shigenobu Kanba, Introducing the concept of modern depression in Japan; An international case vignette survey, Journal of Affective Disorders, 10.1016/j.jad.2011.06.030, 135, 1-3, 66-76, 2011.12, Aim: Japanese psychiatrists have increasingly reported patients with depression that does not seem to fit the criteria of the ICD-10 and the DSM-IV, and which has recently been called modern type depression (MTD). We explored whether MTD is frequently seen in Japan and also in other countries, and if so, how patients with MTD are diagnosed and treated. Methods: The questionnaires, with two case vignettes (traditional type depression (TTD) and MTD), were sent to psychiatrists in Australia, Bangladesh, India, Iran, Japan, Korea, Taiwan, Thailand and the USA. Participants rated their opinions about each case's prevalence in their country, etiology, diagnosis, suicide risk, and treatment using Likert scales. Results: Out of 247 responses (123 from Japan and 124 from other countries), two hundred thirty-nine valid responses were received. MTD was recognized in all participating countries, and especially in urban areas. Generally, the factor of personality was regarded as the most probable cause of MTD. Whereas about 90% of Japanese psychiatrists applied the ICD/DSM criteria to TTD, only about 60% applied the criteria to MTD. Conclusion: Our results indicate that Japan's MTD seems to be occurring in many other countries, and that the present ICD/DSM criteria may not be sufficient to diagnose MTD. Therefore, it could be an important candidate for a new international diagnostic criterion as a subtype of depression. A clear diagnostic framework and consensus on the interventions to treat MTD would be valuable. Further clinical, psychopathological and international epidemiological studies are needed to confirm our preliminary findings of MTD..
118. Takahiro A. Kato, Naotaka Shinfuku, Daisuke Fujisawa, Masaru Tateno, Tetsuya Ishida, Tsuyoshi Akiyama, Norman Sartorius, Alan R. Teo, Tae Young Choi, Anne P. F. Wand, Yatan Pal Singh Balhara, Jane Pei-Chen Chang, Rita Yuan-Feng Chang, Behrang Shadloo, Helal Uddin Ahmed, Tiraya Lerthattasilp, Wakako Umene-Nakano, Hideki Horikawa, Ryohei Matsumoto, Hironori Kuga, Masuo Tanaka, Shigenobu Kanba, Introducing the concept of modern depression in Japan; an international case vignette survey, JOURNAL OF AFFECTIVE DISORDERS, 10.1016/j.jad.2011.06.030, 135, 1-3, 66-76, 2011.12, Aim: Japanese psychiatrists have increasingly reported patients with depression that does not seem to fit the criteria of the ICD-10 and the DSM-IV, and which has recently been called modern type depression (MTD). We explored whether MTD is frequently seen in Japan and also in other countries, and if so, how patients with MTD are diagnosed and treated.
Methods: The questionnaires, with two case vignettes (traditional type depression (TTD) and MTD), were sent to psychiatrists in Australia, Bangladesh, India, Iran, Japan, Korea, Taiwan, Thailand and the USA. Participants rated their opinions about each case's prevalence in their country, etiology, diagnosis, suicide risk, and treatment using Likert scales.
Results: Out of 247 responses (123 from Japan and 124 from other countries), two hundred thirty-nine valid responses were received. MTD was recognized in all participating countries, and especially in urban areas. Generally, the factor of personality was regarded as the most probable cause of MTD. Whereas about 90% of Japanese psychiatrists applied the ICD/DSM criteria to TTD, only about 60% applied the criteria to MID.
Conclusion: Our results indicate that Japan's MID seems to be occurring in many other countries, and that the present ICD/DSM criteria may not be sufficient to diagnose MID. Therefore, it could be an important candidate for a new international diagnostic criterion as a subtype of depression. A clear diagnostic framework and consensus on the interventions to treat MID would be valuable. Further clinical, psychopathological and international epidemiological studies are needed to confirm our preliminary findings of MID. (C) 2011 Elsevier B.V. All rights reserved..
119. Akira Monji, Takahiro Kato, Yoshito Mizoguchi, Hideki Horikawa, Yoshihiro Seki, Shigenobu Kanba, Visual and auditory hallucinations during normal use of paroxetine for treatment of major depressive disorder, Journal of Neuropsychiatry and Clinical Neurosciences, 23, 4, 14-15, 2011.10.
120. Visual and auditory hallucinations during normal use of paroxetine for treatment of major depressive disorder..
121. Takahiro A. Kato, Naotaka Shinfuku, Norman Sartorius, Shigenobu Kanba, Are Japan's hikikomori and depression in young people spreading abroad?, The Lancet, 10.1016/S0140-6736(11)61475-X, 378, 9796, 1070, 2011.09.
122. Takahiro A. Kato, Naotaka Shinfuku, Norman Sartorius, Shigenobu Kanba, Are Japan's hikikomori and depression in young people spreading abroad?, LANCET, 10.1016/S0140-6736(11)61475-X, 378, 9796, 1070-1070, 2011.09.
123. Takahiro A. Kato, Akira Monji, Keiji Yasukawa, Yoshito Mizoguchi, Hideki Horikawa, Yoshihiro Seki, Sadayuki Hashioka, Youn Hee Han, Mina Kasai, Noriyuki Sonoda, Eiichi Hirata, Yasutaka Maeda, Toyoshi Inoguchi, Hideo Utsumi, Shigenobu Kanba, Aripiprazole inhibits superoxide generation from phorbol-myristate-acetate (PMA)-stimulated microglia in vitro
Implication for antioxidative psychotropic actions via microglia, Schizophrenia research, 10.1016/j.schres.2011.03.019, 129, 2-3, 172-182, 2011.07, Altered antioxidant status has been implicated in schizophrenia. Microglia, major sources of free radicals such as superoxide (O2-), play crucial roles in various brain pathologies. Recent postmortem and imaging studies have indicated microglial activation in the brain of schizophrenic patients. We previously demonstrated that atypical antipsychotics including aripiprazole significantly inhibited the release of nitric oxide and proinflammatory cytokines from interferon-γ-stimulated microglia in vitro. Antioxidative effects of antipsychotics via modulating microglial superoxide generation have never been reported. Therefore, we herein investigated the effects of antipsychotics on the O2- generation from phorbol-myristate-acetate (PMA)-stimulated rodent microglia by the electron spin resonance (ESR) spectroscopy and also examined the intracellular mechanism by intracellular Ca2+ imaging and immunostaining. Neuronal damage induced by microglial activation was also investigated by the co-culture experiment.Among various antipsychotics, only aripiprazole inhibited the O2- generation from PMA-stimulated microglia. Aripiprazole proved to inhibit the O2- generation through the cascade of protein kinase C (PKC) activation, intracellular Ca2+ regulation and NADPH oxidase activation via cytosolic p47phox translocation to the plasma/phagosomal membranes. Formation of neuritic beading, induced by PMA-stimulated microglia, was attenuated by pretreatment of aripiprazole.D2R antagonism has long been considered as the primary therapeutic action for schizophrenia. Aripiprazole with D2R partial agonism is effective like other antipsychotics with fewer side effects, while aripiprazole's therapeutic mechanism itself remains unclear. Our results imply that aripiprazole may have psychotropic effects by reducing the microglial oxidative reactions and following neuronal reactions, which puts forward a novel therapeutic hypothesis in schizophrenia research..
124. Takahiro A. Kato, Akira Monji, Keiji Yasukawa, Yoshito Mizoguchi, Hideki Horikawa, Yoshihiro Seki, Sadayuki Hashioka, Youn-Hee Han, Mina Kasai, Noriyuki Sonoda, Eiichi Hirata, Yasutaka Maeda, Toyoshi Inoguchi, Hideo Utsumi, Shigenobu Kanba, Aripiprazole inhibits superoxide generation from phorbol-myristate-acetate (PMA)-stimulated microglia in vitro: Implication for antioxidative psychotropic actions via microglia, SCHIZOPHRENIA RESEARCH, 10.1016/j.schres.2011.03.019, 129, 2-3, 172-182, 2011.07, Altered antioxidant status has been implicated in schizophrenia. Microglia, major sources of free radicals such as superoxide (.O(2)(-)), play crucial roles in various brain pathologies. Recent postmortem and imaging studies have indicated microglial activation in the brain of schizophrenic patients. We previously demonstrated that atypical antipsychotics including aripiprazole significantly inhibited the release of nitric oxide and proinflammatory cytokines from interferon-gamma-stimulated microglia in vitro. Antioxidative effects of antipsychotics via modulating microglial superoxide generation have never been reported. Therefore, we herein investigated the effects of antipsychotics on the .O(2)(-) generation from phorbol-myristate-acetate (PMA)-stimulated rodent microglia by the electron spin resonance (ESR) spectroscopy and also examined the intracellular mechanism by intracellular Ca(2+) imaging and immunostaining. Neuronal damage induced by microglial activation was also investigated by the co-culture experiment.
Among various antipsychotics, only aripiprazole inhibited the .O(2)(-) generation from PMA-stimulated microglia. Aripiprazole proved to inhibit the .O(2)(-) generation through the cascade of protein kinase C (PKC) activation, intracellular Ca(2+) regulation and NADPH oxidase activation via cytosolic p47(phox) translocation to the plasma/phagosomal membranes. Formation of neuritic beading, induced by PMA-stimulated microglia, was attenuated by pretreatment of aripiprazole.
D2R antagonism has long been considered as the primary therapeutic action for schizophrenia. Aripiprazole with D2R partial agonism is effective like other antipsychotics with fewer side effects, while aripiprazole's therapeutic mechanism itself remains unclear. Our results imply that aripiprazole may have psychotropic effects by reducing the microglial oxidative reactions and following neuronal reactions, which puts forward a novel therapeutic hypothesis in schizophrenia research. (C) 2011 Elsevier B.V. All rights reserved..
125. [Views on the new psychiatric specialist certification system from the perspective of those experiencing the postgraduate psychiatric training system in Japan]..
126. Shiori Kato, Takahiro A. Kato, Haruko Nishie, Sankei Nishima, Tomoaki Iwanaga, Akira Monji, Misa Nakano, Hiromichi Takeshita, Masutaka Furue, Successful treatment of chronic urticaria with a Japanese herbal medicine, yokukansan, Journal of Dermatology, 10.1111/j.1346-8138.2010.00937.x, 37, 12, 1066-1067, 2010.12.
127. Takahiro A. Kato, Yuriko Suzuki, Ryoko Sato, Daisuke Fujisawa, Kumi Uehara, Naoki Hashimoto, Yasunori Sawayama, Jun Hayashi, Shigenobu Kanba, Kotaro Otsuka, Development of 2-hour suicide intervention program among medical residents
First pilot trial, Psychiatry and clinical neurosciences, 10.1111/j.1440-1819.2010.02114.x, 64, 5, 531-540, 2010.10, Aim: Suicide is associated not only with primary psychiatric disorders but also with physical disorders. Physicians' education on suicide prevention contributes to reducing suicide. Therefore, medical residents, who contact patients daily and who eventually become primary physicians in each specialty, might be the most appropriate candidates for intervention. In this article, we introduce our newly developed suicide intervention program among medical residents. Methods: We developed a 2-hour suicide intervention program among medical residents, based on the Mental Health First Aid (MHFA), which had originally been developed for the public. The program contains a 1-hour lecture and a 1-hour role-play session. As the first pilot trial, we conducted the program among 44 first-year medical residents at a university hospital and evaluated its effectiveness. Changes in confidence, attitudes and behavior toward suicidal people were evaluated using self-reported questionnaires before, immediately after, and 6 months after the program. Results: Participants' confidence and attitudes significantly improved after the program. The total mean score (standard deviation) of the Suicide Intervention Response Inventory improved from 18.4 (2.0) before the intervention to 19.4 (2.0) immediately after the intervention. However, the effectiveness was limited after 6 months. In the course of 6 months, the participants learned to apply the MHFA principles in their daily clinical practice. Conclusion: Our newly developed brief suicide intervention program demonstrating its effectiveness among medical residents should be modified in order to be more effective in the long term. The next trial with a control group ought to be conducted to evaluate our developed program..
128. Takahiro A. Kato, Masaru Tateno, Wakako Umene-Nakano, Yatan P.S. Balhara, Alan R. Teo, Daisuke Fujisawa, Ryuji Sasaki, Tetsuya Ishida, Shigenobu Kanba, Impact of biopsychosocial factors on psychiatric training in Japan and overseas
Are psychiatrists oriented to mind, brain, or sociocultural issues?, Psychiatry and clinical neurosciences, 10.1111/j.1440-1819.2010.02133.x, 64, 5, 520-530, 2010.10, Aim: To clarify the impact of biopsychosocial factors on psychiatric training under the new and traditional postgraduate medical education system in Japan and to compare them with young psychiatrists from other countries. Methods: Psychiatric residents and early-career psychiatrists were recruited in Japan and other countries. Using mail-based and web-based self-administered questionnaires, we evaluated participants' demographic information, motivation to become psychiatrists, interest and commitment to various aspects of psychiatry, and reactions to a case vignette, focusing on biopsychosocial factors. Results: A total of 137 responses, 81 from Japan and 56 from other countries, were collected. Before starting psychiatric training, Japanese participants showed a strong interest in 'mind' and less interest in 'brain' and 'environmental factors', while the interest in 'brain' and 'environmental factors' is presently as high as that in 'mind.' Japanese participants reported less commitment to their training toward ICD/DSM-based diagnosis, interview, pharmacotherapy, psychosocial treatment and epidemiology, compared with participants from other countries. In particular, Japanese participants showed less commitment to their training in suicide prevention, despite their perception of its high importance due to a high suicide rate in Japan. Suicide risk of a case vignette proved to be differently assessed according to participants' commitment levels to each aspect of psychiatry. Conclusion: Our results suggest that young psychiatrists' attitudes concerning the biopsychosocial model generally become well-balanced with psychiatric training, however sociocultural factors do not seem to be well represented in the Japanese psychiatric training system. Additional training on sociocultural issues, such as suicide in Japan, should be considered..
129. Hideki Horikawa, Takahiro A. Kato, Yoshito Mizoguchi, Akira Monji, Yoshihiro Seki, Takatoshi Ohkuri, Leo Gotoh, Megumi Yonaha, Tadashi Ueda, Sadayuki Hashioka, Shigenobu Kanba, Inhibitory effects of SSRIs on IFN-γ induced microglial activation through the regulation of intracellular calcium, Progress in Neuro-Psychopharmacology and Biological Psychiatry, 10.1016/j.pnpbp.2010.07.015, 34, 7, 1306-1316, 2010.10, Microglia, which are a major glial component of the central nervous system (CNS), have recently been suggested to mediate neuroinflammation through the release of pro-inflammatory cytokines and nitric oxide (NO). Microglia are also known to play a critical role as resident immunocompetent and phagocytic cells in the CNS. Immunological dysfunction has recently been demonstrated to be associated with the pathophysiology of depression. However, to date there have only been a few studies on the relationship between microglia and depression. We therefore investigated if antidepressants can inhibit microglial activation in vitro. Our results showed that the selective serotonin reuptake inhibitors (SSRIs) paroxetine and sertraline significantly inhibited the generation of NO and tumor necrosis factor (TNF)-α from interferon (IFN)-γ-activated 6-3 microglia. We further investigated the intracellular signaling mechanism underlying NO and TNF-α release from IFN-γ-activated 6-3 microglia. Our results suggest that paroxetine and sertraline may inhibit microglial activation through inhibition of IFN-γ-induced elevation of intracellular Ca2+. Our results suggest that the inhibitory effect of paroxetine and sertraline on microglial activation may not be a prerequisite for antidepressant function, but an additional beneficial effect..
130. Masaru Tateno, Takahiro Kato, Wakako Nakano, Shigenobu Kanba, Jun Nakamura, Toshikazu Saito, Differences in the preferred antipsychotics for acute schizophrenia among young psychiatrists in two regions of Japan, Asian Journal of Psychiatry, 10.1016/j.ajp.2010.03.005, 3, 2, 60-63, 2010.06, Background: Effective emergency intervention for acute schizophrenia is of great concern to psychiatrists. To investigate whether differences in attitudes toward pharmacotherapy exist in the emergency setting, we surveyed two regions of Japan. Methods: The subjects were 100 psychiatrists. The clinical experience of all subjects was not more than 15 years. A questionnaire with a case vignette was sent to them and returned anonymously. Thirty-five out of 42 subjects in Hokkaido and 30 out of 58 subjects in Fukuoka responded. Results: We found a difference in the preferred route of administration of haloperidol, the agent chosen by 46.2% of the respondents. Most psychiatrists in Hokkaido preferred intravenous administration, but none of the Fukuoka psychiatrists chose this route preferring intramuscular administration. The mean dose of haloperidol was significantly higher in Hokkaido (7.29 ± 2.5 mg) compared to that in Fukuoka (5.56 ± 1.7 mg). Conclusion: The difference in preferred route of administration and dose of haloperidol probably reflects the content of training at each hospital and suggests that early training determines the subsequent clinical custom of each psychiatrist..
131. Masaru Tateno, Takahiro Kato, Wakako Nakano, Shigenobu Kanba, Jun Nakamura, Toshikazu Saito, Differences in the preferred antipsychotics for acute schizophrenia among young psychiatrists in two regions of Japan, Asian Journal of Psychiatry, 10.1016/j.ajp.2010.03.005, 3, 2, 60-63, 2010.06, Background: Effective emergency intervention for acute schizophrenia is of great concern to psychiatrists. To investigate whether differences in attitudes toward pharmacotherapy exist in the emergency setting, we surveyed two regions of Japan. Methods: The subjects were 100 psychiatrists. The clinical experience of all subjects was not more than 15 years. A questionnaire with a case vignette was sent to them and returned anonymously. Thirty-five out of 42 subjects in Hokkaido and 30 out of 58 subjects in Fukuoka responded. Results: We found a difference in the preferred route of administration of haloperidol, the agent chosen by 46.2% of the respondents. Most psychiatrists in Hokkaido preferred intravenous administration, but none of the Fukuoka psychiatrists chose this route preferring intramuscular administration. The mean dose of haloperidol was significantly higher in Hokkaido (7.29 ± 2.5 mg) compared to that in Fukuoka (5.56 ± 1.7 mg). Conclusion: The difference in preferred route of administration and dose of haloperidol probably reflects the content of training at each hospital and suggests that early training determines the subsequent clinical custom of each psychiatrist. © 2010 Elsevier B.V. All rights reserved..
132. Masaru Tateno, Takahiro Kato, Wakako Nakano, Alan R. Teo, Atsuo Nakagawa, Kaya Miyajima, Shigenobu Kanba, Jun Nakamura, Toshikazu Saito, Attitudes of early-career psychiatrists in Japan toward child and adolescent psychiatry and their career decision, Psychiatry and clinical neurosciences, 10.1111/j.1440-1819.2010.02062.x, 64, 2, 199-201, 2010.04, The aim of the present study was to carry out a national survey to understand the attitude of early-career psychiatrists toward child and adolescent psychiatry (CAP). The subjects were 348 early-career psychiatrists. A questionnaire was sent to the subjects and returned anonymously. A total of 234 subjects (67.2%) responded. Ten out of 115 psychiatrists (8.9%) in their first-third year of experience, and 18 of 119 psychiatrists (15.1%) in their fourth-10th year answered that they had interest in CAP. Psychiatry rotations with adequate CAP cases may be necessary to attract early-career psychiatrists to CAP..
133. Masaru Tateno, Takahiro Kato, Wakako Nakano, Alan R. Teo, Atsuo Nakagawa, Kaya Miyajima, Shigenobu Kanba, Jun Nakamura, Toshikazu Saito, Attitudes of early-career psychiatrists in Japan toward child and adolescent psychiatry and their career decision, PSYCHIATRY AND CLINICAL NEUROSCIENCES, 10.1111/j.1440-1819.2010.02062.x, 64, 2, 199-201, 2010.04, The aim of the present study was to carry out a national survey to understand the attitude of early-career psychiatrists toward child and adolescent psychiatry (CAP). The subjects were 348 early-career psychiatrists. A questionnaire was sent to the subjects and returned anonymously. A total of 234 subjects (67.2%) responded. Ten out of 115 psychiatrists (8.9%) in their first-third year of experience, and 18 of 119 psychiatrists (15.1%) in their fourth-10th year answered that they had interest in CAP. Psychiatry rotations with adequate CAP cases may be necessary to attract early-career psychiatrists to CAP..
134. Takahiro A. Kato, Masaru Tateno, Wakako Umene-Nakano, Yatan P. S. Balhara, Alan R. Teo, Daisuke Fujisawa, Ryuji Sasaki, Tetsuya Ishida, Shigenobu Kanba, Impact of biopsychosocial factors on psychiatric training in Japan and overseas: Are psychiatrists oriented to mind, brain, or sociocultural issues?, PSYCHIATRY AND CLINICAL NEUROSCIENCES, 10.1111/j.1440-1819.2010.02133.x, 64, 5, 520-530, 2010.04, Aim:
To clarify the impact of biopsychosocial factors on psychiatric training under the new and traditional postgraduate medical education system in Japan and to compare them with young psychiatrists from other countries.
Methods:
Psychiatric residents and early-career psychiatrists were recruited in Japan and other countries. Using mail-based and web-based self-administered questionnaires, we evaluated participants' demographic information, motivation to become psychiatrists, interest and commitment to various aspects of psychiatry, and reactions to a case vignette, focusing on biopsychosocial factors.
Results:
A total of 137 responses, 81 from Japan and 56 from other countries, were collected. Before starting psychiatric training, Japanese participants showed a strong interest in 'mind' and less interest in 'brain' and 'environmental factors', while the interest in 'brain' and 'environmental factors' is presently as high as that in 'mind.' Japanese participants reported less commitment to their training toward ICD/DSM-based diagnosis, interview, pharmacotherapy, psychosocial treatment and epidemiology, compared with participants from other countries. In particular, Japanese participants showed less commitment to their training in suicide prevention, despite their perception of its high importance due to a high suicide rate in Japan. Suicide risk of a case vignette proved to be differently assessed according to participants' commitment levels to each aspect of psychiatry.
Conclusion:
Our results suggest that young psychiatrists' attitudes concerning the biopsychosocial model generally become well-balanced with psychiatric training, however sociocultural factors do not seem to be well represented in the Japanese psychiatric training system. Additional training on sociocultural issues, such as suicide in Japan, should be considered..
135. [Issues and the current situation of the new compulsory residency training program in Japan: the results of an attitude survey for young career psychiatrists]..
136. Tateno M, Kato T, Nakano W, Kanba S, Nakamura J, Saito T, Differences in the preferred route of administration of haloperidol for acute schizophrenia among young psychiatrists in two regions of Japan., Asian Journal of Psychiatry, 3.0, 60–63, 2010.01.
137. Wakako Nakano, Takahiro Kato, Masaru Tateno, Keisuke Ikari, Teppei Tanaka, Takashi Nakamae, Tsutomu Hojusan, Jun Nakamura, A thought on postgraduate psychiatric education from the viewpoint of residents in the latter stage of training based on the system of training of psychiatric specialists--the latter part of the psychiatric training at university hospitals, Seishin shinkeigaku zasshi = Psychiatria et neurologia Japonica, 111, 10, 1214-1219, 2009.12.
138. Wakako Nakano, Takahiro Kato, Masaru Tateno, Jun Nakamura, Postgraduate psychiatric training in Japan, Seishin shinkeigaku zasshi = Psychiatria et neurologia Japonica, 111, 10, 1246-1249, 2009.12.
139. Takahiro Kato, Masaru Tateno, Wakako Nakano, Yatan Pal Singh Balhara, R. Teo Teo, Daisuke Fujisawa, Ryuji Sasaki, Mai Uchida, Re-evaluation of the "road to becoming a psychiatrist"--learning from the interaction with young psychiatrists from overseas, Seishin shinkeigaku zasshi = Psychiatria et neurologia Japonica, 111, 10, 1226-1233, 2009.12.
140. Yoshito Mizoguchi, Akira Monji, Takahiro Kato, Yoshihiro Seki, Leo Gotoh, Hideki Horikawa, Satoshi O. Suzuki, Toru Iwaki, Miyuki Yonaha, Sadayuki Hashioka, Shigenobu Kanba, Brain-derived neurotrophic factor induces sustained elevation of intracellular Ca2+ in rodent microglia, Journal of Immunology, 10.4049/jimmunol.0901326, 183, 12, 7778-7786, 2009.12, Microglia are intrinsic immune cells that release factors, including proinflammatory cytokines, NO, and neurotrophins, following activation after disturbance in the brain. Elevation of intracellular Ca2+ concentration ([Ca2+]i) is important for microglial functions, such as the release of cytokines and NO from activated microglia. There is increasing evidence suggesting that pathophysiology of neuropsychiatric disorders is related to the inflammatory responses mediated by microglia. Brain-derived neurotrophic factor (BDNF) is a neurotrophin well known for its roles in the activation of microglia as well as in pathophysiology and/or treatment of neuropsychiatric disorders. In this study, we observed that BDNF induced a sustained increase in [Ca2+]i through binding with the truncated tropomyosin-related kinase B receptor, resulting in activation of the PLC pathway and store-operated calcium entry in rodent microglial cells. RT-PCR and immunocytochemical techniques revealed that truncated tropomyosinrelated kinase B-T1 receptors were highly expressed in rodent microglial cells. Sustained activation of store-operated calcium entry occurred after brief BDNF application and contributed to the maintenance of sustained [Ca2+]i elevation. Pretreatment with BDNF significantly suppressed the release of NO from activated microglia. Additionally, pretreatment of BDNF suppressed the IFN-γ-induced increase in [Ca2+]i, along with a rise in basal levels of [Ca2+]i in rodent microglial cells. We show direct evidence that rodent microglial cells are able to respond to BDNF, which may be important for the regulation of inflammatory responses, and may also be involved in the pathophysiology and/or the treatment of neuropsychiatric disorders..
141. Yoshito Mizoguchi, Akira Monji, Takahiro Kato, Yoshihiro Seki, Leo Gotoh, Hideki Horikawa, Satoshi O. Suzuki, Toru Iwaki, Miyuki Yonaha, Sadayuki Hashioka, Shigenobu Kanba, Brain-Derived Neurotrophic Factor Induces Sustained Elevation of Intracellular Ca2+ in Rodent Microglia, JOURNAL OF IMMUNOLOGY, 10.4049/jimmunol.0901326, 183, 12, 7778-7786, 2009.12, Microglia are intrinsic immune cells that release factors, including proinflammatory cytokines, NO, and neurotrophins, following activation after disturbance in the brain. Elevation of intracellular Ca2+ concentration ([Ca2+](i)) is important for microglial functions, such as the release of cytokines and NO from activated microglia. There is increasing evidence suggesting that pathophysiology of neuropsychiatric disorders is related to the inflammatory responses mediated by microglia. Brain-derived neurotrophic factor (BDNF) is a neurotrophin well known for its roles in the activation of microglia as well as in pathophysiology and/or treatment of neuropsychiatric disorders. In this study, we observed that BDNF induced a sustained increase in [Ca2+]i through binding with the truncated tropomyosin-related kinase B receptor, resulting in activation of the PLC pathway and store-operated calcium entry in rodent microglial cells. RT-PCR and immunocytochemical techniques revealed that truncated tropomyosin-related kinase B-T1 receptors were highly expressed in rodent microglial cells. Sustained activation of store-operated calcium entry occurred after brief BDNF application and contributed to the maintenance of sustained [Ca2+]i elevation. Pretreatment with. BDNF significantly suppressed the release of NO from activated microglia. Additionally, pretreatment of BDNF suppressed the IIFN-gamma-induced increase in [Ca2+]i, along with a rise in basal levels of [Ca2+]i in rodent microglial cells. We show direct evidence that rodent microglial cells are able to respond to BDNF, which may be important for the regulation of inflammatory responses, and may also be involved in the pathophysiology and/or the treatment of neuropsychiatric disorders. The Journal of Immunology, 2009, 183: 7778-7786..
142. [Re-evaluation of the "road to becoming a psychiatrist"--learning from the interaction with young psychiatrists from overseas]..
143. Masaru Tateno, Kanna Sugiura, Kumi Uehara, Daisuke Fujisawa, Yueren Zhao, Naoki Hashimoto, Hidehiko Takahashi, Naofumi Yoshida, Takahiro Kato, Wakako Nakano, Yosuke Wake, Tomohiro Shirasaka, Seiju Kobayashi, Soichiro Sato, Attitude of young psychiatrists toward coercive measures in psychiatry
A case vignette study in Japan, International Journal of Mental Health Systems, 10.1186/1752-4458-3-20, 3, 2009.09, Background: Every psychiatrist must pay careful attention to avoid violating human rights when initiating coercive treatments such as seclusion and restraint. However, these interventions are indispensable in clinical psychiatry, and they are often used as strategies to treat agitated patients. In this study, we investigated young psychiatrists' attitudes toward psychiatric coercive measures.Methods: A total of 183 young psychiatrists participated as subjects in our study. A questionnaire with a case vignette describing a patient with acute psychosis was sent to the study subjects via the Internet or by mail. This questionnaire included scoring the necessity for hospitalization, and the likelihood of prescribing seclusion and/or restraint, on a 9-point Likert scale (with 9 indicating strong agreement).Results: There was general agreement among the study subjects that the case should be admitted to a hospital (8.91 ± 0.3) and secluded (8.43 ± 1.0). The estimated length of hospitalization was 13.53 ± 6.4 weeks. Regarding the likelihood of prescribing restraint, results showed great diversity (5.14 ± 2.5 on 9-point scale); psychiatrists working at general hospitals scored significantly higher (6.25 ± 2.5) than those working at university hospitals (5.02 ± 2.3) or psychiatric hospitals (4.15 ± 2.6). A two-group comparison of the length of inpatient care revealed a significant difference between those psychiatrists who scored 1-3 (n = 55, 14.22 ± 7.4 wks) and those who scored 7-9 (n = 62, 12.22 ± 4.0) regarding the need to use restraint.Conclusion: Our results may reflect the current dilemma in Japanese psychiatry wherein psychiatrists must initiate coercive measures to shorten hospitalization stays. This study prompted its subject psychiatrists to consider coercive psychiatric treatments..
144. 藤澤 大介, Attitude of young psychiatrists toward coercive measures in psychiatry: A case vignette study in Japan, International Journal of Mental Health Systems, 3(1), 20, 2009.09.
145. Kumi Uehara, Takahiro Kato, Naoki Hashimoto, Yosuke Wake, Tetsuhei Tanaka, Toshiaki Baba, Daisuke Fujisawa, Study by young psychiatrists and significance and future challenge through their interactions--the scenes for learning and mutual support, Seishin shinkeigaku zasshi = Psychiatria et neurologia Japonica, 111, 2, 221-226, 2009.06.
146. Akira Monji, Masashi Takita, Takaaki Samejima, Toshihiro Takaishi, Kazuhito Hashimoto, Hiroyuki Matsunaga, Mariko Oda, Yasuhisa Sumida, Yoshito Mizoguchi, Takahiro Kato, Hideki Horikawa, Shigenobu Kanba, Effect of yokukansan on the behavioral and psychological symptoms of dementia in elderly patients with Alzheimer's disease, Progress in Neuro-Psychopharmacology and Biological Psychiatry, 10.1016/j.pnpbp.2008.12.008, 33, 2, 308-311, 2009.03, Objective: The aim of this study was to investigate the effects of yokukansan (YKS) on the behavioral and psychological symptoms of dementia (BPSD) in elderly patients with Alzheimer's disease (AD). Methods: Fifteen patients with AD (mean age: 80.2 ± 4.0 years) participated in the study. The Mini-Mental State Examination (MMSE) was used for the assessment of cognitive function. BPSD were evaluated using the Neuropsychiatric Inventory (NPI). The Barthel Index was used for the assessment for the activities of daily living (ADL). The treatment with YKS along with sulpiride, a dopamine D2 selective antipsychotic, was performed for 12 weeks. Results: Fourteen patients completed the trial. After the 12 weeks of treatment with YKS, significant improvement of the mean NPI score was observed while no significant improvement was observed in the control group. The average dose of sulpiride at the end of the present study was less in the YKS group than in the control group. The MMSE results did not change either in the YKS group or in the control group. The Barthel Index did not significantly change either in the YKS group or in the control group. No serious adverse effects were noted. Conclusions: Twelve weeks of the YKS treatment significantly improved BPSD with less antipsychotics in elderly patients with AD. The YKS treatment did not cause any cognitive decline or ADL decline and no serious adverse effects were noted. The present study suggests that YKS is beneficial for the treatment of BPSD and that it can possibly reduce the doses of antipsychotics required for the treatment of BPSD. Further studies with larger patient populations using a double-blind placebo-controlled design should be performed..
147. Akira Monji, Masashi Takita, Takaaki Samejima, Toshihiro Takaishi, Kazuhito Hashimoto, Hiroyuki Matsunaga, Mariko Oda, Yasuhisa Sumida, Yoshito Mizoguchi, Takahiro Kato, Hideki Horikawa, Shigenobu Kanba, Effect of yokukansan on the behavioral and psychological symptoms of dementia in elderly patients with Alzheimer's disease, Progress in Neuro-Psychopharmacology and Biological Psychiatry, 10.1016/j.pnpbp.2008.12.008, 33, 2, 308-311, 2009.03, Objective: The aim of this study was to investigate the effects of yokukansan (YKS) on the behavioral and psychological symptoms of dementia (BPSD) in elderly patients with Alzheimer's disease (AD). Methods: Fifteen patients with AD (mean age: 80.2 ± 4.0 years) participated in the study. The Mini-Mental State Examination (MMSE) was used for the assessment of cognitive function. BPSD were evaluated using the Neuropsychiatric Inventory (NPI). The Barthel Index was used for the assessment for the activities of daily living (ADL). The treatment with YKS along with sulpiride, a dopamine D2 selective antipsychotic, was performed for 12 weeks. Results: Fourteen patients completed the trial. After the 12 weeks of treatment with YKS, significant improvement of the mean NPI score was observed while no significant improvement was observed in the control group. The average dose of sulpiride at the end of the present study was less in the YKS group than in the control group. The MMSE results did not change either in the YKS group or in the control group. The Barthel Index did not significantly change either in the YKS group or in the control group. No serious adverse effects were noted. Conclusions: Twelve weeks of the YKS treatment significantly improved BPSD with less antipsychotics in elderly patients with AD. The YKS treatment did not cause any cognitive decline or ADL decline and no serious adverse effects were noted. The present study suggests that YKS is beneficial for the treatment of BPSD and that it can possibly reduce the doses of antipsychotics required for the treatment of BPSD. Further studies with larger patient populations using a double-blind placebo-controlled design should be performed. © 2008 Elsevier Inc. All rights reserved..
148. [Study by young psychiatrists and significance and future challenge through their interactions--the scenes for learning and mutual support]..
149. [A thought on postgraduate psychiatric education from the viewpoint of residents in the latter stage of training based on the system of training of psychiatric specialists--the latter part of the psychiatric training at university hospitals]..
150. Takahiro Kato, Yoshito Mizoguchi, Akira Monji, Hideki Horikawa, Satoshi O. Suzuki, Yoshihiro Seki, Toru Iwaki, Sadayuki Hashioka, Shigenobu Kanba, Inhibitory effects of aripiprazole on interferon-γ-induced microglial activation via intracellular Ca2+ regulation in vitro, Journal of Neurochemistry, 10.1111/j.1471-4159.2008.05435.x, 106, 2, 815-825, 2008.07, The activation of the inflammatory/immunological response system is suggested to be related to the pathophysiology of schizophrenia. Aripiprazole is a novel atypical antipsychotic, which is a high-affinity dopamine D2 receptor partial agonist. Atypical antipsychotics, all of which have dopamine D2 receptor antagonism, have recently reported to have significantly inhibitory effects on interferon (IFN)-γ-induced microglial activation in vitro. In the present study, we investigated whether or not aripiprazole also has anti-inflammatory effect on IFN-γ-induced microglial activation. Not quinpirole, dopamine D2 full agonist, but aripiprazole significantly inhibited the generation of nitric oxide (NO) and tumor necrosis factor (TNF)-α from IFN-γ-activated microglia and suppressed the IFN-γ-induced elevation of intracellular Ca2+ concentrations ([Ca2+]i) in murine microglial cells. Increased [Ca2+]i has been reported to be required, but by itself not sufficient, for the release of NO and certain cytokines. As a result, we can speculate that aripiprazole may inhibit IFN-γ-induced microglial activation through the suppression of IFN-γ-induced elevation of [Ca2+]i in microglia. Our results demonstrated that not only antipsychotics which have dopamine D2 receptor antagonism but also aripiprazole have anti-inflammatory effects via the inhibition of microglial activation. Antipsychotics may therefore have a potentially useful therapeutic effect on patients with schizophrenia by reducing the microglial inflammatory reactions..
151. Takahiro Kato, Yoshito Mizoguchi, Akira Monji, Hideki Horikawa, Satoshi O. Suzuki, Yoshihiro Seki, Toru Iwaki, Sadayuki Hashioka, Shigenobu Kanba, Inhibitory effects of aripiprazole on interferon-gamma-induced microglial activation via intracellular Ca2+ regulation in vitro, JOURNAL OF NEUROCHEMISTRY, 10.1111/j.1471-4159.2008.05435.x, 106, 2, 815-825, 2008.07, The activation of the inflammatory/immunological response system is suggested to be related to the pathophysiology of schizophrenia. Aripiprazole is a novel atypical antipsychotic, which is a high-affinity dopamine D-2 receptor partial agonist. Atypical antipsychotics, all of which have dopamine D-2 receptor antagonism, have recently reported to have significantly inhibitory effects on interferon (IFN)-gamma-induced microglial activation in vitro. In the present study, we investigated whether or not aripiprazole also has anti-inflammatory effect on IFN-gamma-induced microglial activation. Not quinpirole, dopamine D-2 full agonist, but aripiprazole significantly inhibited the generation of nitric oxide (NO) and tumor necrosis factor (TNF)-alpha from IFN-gamma-activated microglia and suppressed the IFN-gamma-induced elevation of intracellular Ca2+ concentrations ([Ca2+](i)) in murine microglial cells. Increased [Ca2+](i) has been reported to be required, but by itself not sufficient, for the release of NO and certain cytokines. As a result, we can speculate that aripiprazole may inhibit IFN-gamma-induced microglial activation through the suppression of IFN-gamma-induced elevation of [Ca2+](i) in microglia. Our results demonstrated that not only antipsychotics which have dopamine D-2 receptor antagonism but also aripiprazole have anti-inflammatory effects via the inhibition of microglial activation. Antipsychotics may therefore have a potentially useful therapeutic effect on patients with schizophrenia by reducing the microglial inflammatory reactions..
152. Qian Bian, Takahiro Kato, Akira Monji, Sadayuki Hashioka, Yoshito Mizoguchi, Hideki Horikawa, Shigenobu Kanba, The effect of atypical antipsychotics, perospirone, ziprasidone and quetiapine on microglial activation induced by interferon-γ, Progress in Neuro-Psychopharmacology and Biological Psychiatry, 10.1016/j.pnpbp.2007.06.031, 32, 1, 42-48, 2008.01, 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-α release from activated microglia. Antipsychotics, especially perospirone and quetiapine may have an anti-inflammatory effect via the inhibition of microglial activation, which is not only directly toxic to neurons but also has an inhibitory effect on neurogenesis and oligodendrogenesis, both of which have been reported to play a crucial role in the pathology of schizophrenia..
153. Qian Bian, Takahiro Kato, Akira Monji, Sadayuki Hashioka, Yoshito Mizoguchi, Hideki Horikawa, Shigenobu Kanba, The effect of atypical antipsychotics, perospirone, ziprasidone and quetiapine on microglial activation induced by interferon-gamma, PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY, 10.1016/j.pnpbp.2007.06.031, 32, 1, 42-48, 2008.01, 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 not only directly toxic to neurons but also has an inhibitory effect on neurogenesis and oligodendrogenesis, both of which have been reported to play a crucial role in the pathology of schizophrenia. (c) 2007 Elsevier Inc. All rights reserved..
154. Reiko Sato, Takahiro Kato, Kimi Suenaga, Daisuke Fujisawa, Kumi Uehara, Outcome assessment of clinical training of young physicians in psychiatry--from the results of a multi-center survey conducted by the Japanese Organization of Young Psychiatrists, Seishin shinkeigaku zasshi = Psychiatria et neurologia Japonica, 109, 11, 1072-1081, 2007.12.
155. Kaya Miyajima, Daisuke Fujisawa, Atsuo Nakagawa, Takahiro Kato, Psychiatric training at university hospitals--a viewpoint of the first psychiatrists who were trained at the latter part of the new system, Seishin shinkeigaku zasshi = Psychiatria et neurologia Japonica, 109, 11, 1039-1044, 2007.12.
156. Current status and the issues involving young psychiatrists in the process of acquiring a professional status--a survey on the attitudes toward psychiatric training, psychiatric care and psychiatric medicine.
157. Takahiro Kato, Naoki Hashimoto, Reiko Sato, Yayoi Koizumi, Atsuo Nakagawa, Daisuke Fujisawa, Kumi Uehara, Current status and the issues involving young psychiatrists in the process of acquiring a professional status--a survey on the attitudes toward psychiatric training, psychiatric care and psychiatric medicine, Seishin shinkeigaku zasshi = Psychiatria et neurologia Japonica, 109, 11, 1045-1049, 2007.11.
158. Sadayuki Hashioka, Andis Klegeris, Akira Monji, Takahiro Kato, Makoto Sawada, Patrick L. McGeer, Shigenobu Kanba, Antidepressants inhibit interferon-γ-induced microglial production of IL-6 and nitric oxide, Experimental Neurology, 10.1016/j.expneurol.2007.03.022, 206, 1, 33-42, 2007.07, Circumstantial evidence has suggested that activated microglia may be associated with the pathogenesis of depression. Pro-inflammatory cytokines may also be involved. Therefore, we examined the effects of various types of antidepressants, as well as the mood-stabilizer lithium chloride, on interferon-γ (IFN-γ)-induced microglial production of the pro-inflammatory mediators interleukin-6 (IL-6) and nitric oxide (NO). Treatment of the murine microglial 6-3 cells with 100 U/ml of IFN-γ resulted in an eightfold increase in IL-6 and a tenfold increase in NO into the culture medium. Pretreatment with the selective serotonin reuptake inhibitor fluvoxamine, the relatively selective noradrenaline reuptake inhibitor reboxetine, or the non-selective monoaminergic reuptake inhibitor imipramine, significantly inhibited IL-6 and NO production in a dose-dependent manner. These inhibitions were reversed significantly by SQ 22536, a cyclic adenosine monophosphate (cAMP) inhibitor, and, except for reboxetine, by the protein kinase A (PKA) inhibitor Rp-adenosine3′,5′-cyclic monophosphorothioate triethylammonium salt (Rp-3′,5′-cAMPS). Lithium chloride, which is believed to act by inhibiting the calcium-dependent release of noradrenaline, had a different spectrum of action on microglial 6-3 cells. It enhanced IFN-γ-stimulated IL-6 production and inhibited NO production. The inhibitory effect of lithium chloride was not reversed by either SQ 22536 or Rp-3′,5′-cAMPS. These results suggest that antidepressants have inhibitory effects on IFN-γ-activated microglia and these effects are, at least partially, mediated by the cAMP-dependent PKA pathway. On the other hand, the mood stabilizer and anti-manic agent lithium chloride has mixed effects on IFN-γ-induced microglial activation..
159. Takahiro Kato, Akira Monji, Sadayuki Hashioka, Shigenobu Kanba, Risperidone significantly inhibits interferon-γ-induced microglial activation in vitro, Schizophrenia research, 10.1016/j.schres.2007.01.019, 92, 1-3, 108-115, 2007.05, Microglia has recently been regarded to be a mediator of neuroinflammation via the release of proinflammatory cytokines, nitric oxide (NO) and reactive oxygen species (ROS) in the central nervous system (CNS). Microglia has thus been reported to play an important role in the pathology of neurodegenerative disease, such as Alzheimer's disease (AD) and Parkinson's disease (PD). The pathological mechanisms of schizophrenia remain unclear while some recent neuroimaging studies suggest even schizophrenia may be a kind of neurodegenerative disease. Risperidone has been reported to decrease the reduction of MRI volume during the clinical course of schizophrenia. Many recent studies have demonstrated that immunological mechanisms via such as interferon (IFN)-γ and cytokines might be relevant to the pathophysiology of schizophrenia. In the present study, we thus investigated the effects of risperidone on the generation of nitric oxide, inducible NO synthase (iNOS) expression and inflammatory cytokines: interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α by IFN-γ-activated microglia by using Griess assay, Western blotting and ELISA, respectively. In comparison with haloperidol, risperidone significantly inhibited the production of NO and proinflammatory cytokines by activated microglia. The iNOS levels of risperidone-treated cells were much lower than those of the haloperidol-treated cells. Antipsychotics, especially risperidone may have an anti-inflammatory effect via the inhibition of microglial activation, which is not only directly toxic to neurons but also has an inhibitory effect on neurogenesis and oligodendrogenesis, both of which have been reported to play a crucial role in the pathology of schizophrenia..
160. Takahiro Kato, Akira Monji, Sadayuki Hashioka, Shigenobu Kanba, Risperidone significantly inhibits interferon-gamma-induced microglial activation in vitro, SCHIZOPHRENIA RESEARCH, 10.1016/j.schres.2007.01.019, 92, 1-3, 108-115, 2007.05, Microglia has recently been regarded to be a mediator of neuroinflammation via the release of proinflammatory cytokines, nitric oxide (NO) and reactive oxygen species (ROS) in the central nervous system (CNS). Microglia has thus been reported to play an important role in the pathology of neurodegenerative disease, such as Alzheimer's disease (AD) and Parkinson's disease (PD). The pathological mechanisms of schizophrenia remain unclear while some recent neuroimaging studies suggest even schizophrenia may be a kind of neurodegenerative disease. Risperidone has been reported to decrease the reduction of MRI volume during the clinical course of schizophrenia. Many recent studies have demonstrated that immunological mechanisms via such as interferon (IFN)-gamma and cytokines might be relevant to the pathophysiology of schizophrenia. In the present study, we thus investigated the effects of risperidone on the generation of nitric oxide, inducible NO synthase (iNOS) expression and inflammatory cytokines: interleukin (IL)-1 beta, IL-6 and tumor necrosis factor (TNF)-alpha by IFN-gamma-activated microglia by using Griess assay, Western blotting and ELISA, respectively. In comparison with haloperidol, rispetidone significantly inhibited the production of NO and proinflammatory cytokines by activated microglia. The iNOS levels of risperidone-treated cells were much lower than those of the haloperidol-treated cells. Antipsychotics, especially risperidone may have an anti-inflammatory effect via the inhibition of microglial activation, which is not only directly toxic to neurons but also has an inhibitory effect on neurogenesis and oligodendrogenesis, both of which have been reported to play a crucial role in the pathology of schizophrenia. (c) 2007 Elsevier B.V. All rights reserved..
161. Sadayuki Hashioka, Youn Hee Han, Shunsuke Fujii, Takahiro Kato, Akira Monji, Hideo Utsumi, Makoto Sawada, Hiroshi Nakanishi, Shigenobu Kanba, Phosphatidylserine and phosphatidylcholine-containing liposomes inhibit amyloid β and interferon-γ-induced microglial activation, Free Radical Biology and Medicine, 10.1016/j.freeradbiomed.2006.12.003, 42, 7, 945-954, 2007.04, There is increasing evidence that microglial activation is one of the major pathogenic factors for Alzheimer's disease (AD) and the inhibition of the inflammatory activation of the microglia thus appears to be neuroprotective and a potentially useful treatment for AD. Phospholipids such as phosphatidylserine (PS) and phosphatidylcholine (PC) have been reported to modulate the immune function of phagocytes. In addition, PS has been reported to be a nootropics that can be used as nonprescription memory or cognitive enhancers. We therefore evaluated the effects of liposomes, which comprise both PS and PC (PS/PC liposomes), on the microglial production of tumor necrosis factor-α (TNF-α), nitric oxide (NO), and superoxide ({radical dot}O2-) induced by amyloid β (Aβ) and interferon-γ (IFN-γ). Pretreatment of microglia with PS/PC liposomes considerably inhibited the TNF-α, NO and {radical dot}O2- production induced by Aβ/IFN-γ. These results suggest that PS/PC liposomes have both neuroprotective and antioxidative properties through the inhibition of microglial activation, thus supporting the nootropic and antidementia effect of PS..
162. Sadayuki Hashioka, Youn-Hee Han, Shunsuke Fujii, Takahiro Kato, Akira Monji, Hideo Utsumi, Makoto Sawada, Hiroshi Nakanishi, Shigenobu Kanba, Phosphatidylserine and phosphatidylcholine-containing liposomes inhibit amyloid beta and interferon-gamma-induced microglial activation, FREE RADICAL BIOLOGY AND MEDICINE, 10.1016/j.freeradbiomed.2006.12.003, 42, 7, 945-954, 2007.04, There is increasing evidence that microglial activation is one of the major pathogenic factors for Alzheimer's disease (AD) and the inhibition of the inflammatory activation of the microglia thus appears to be neuroprotective and a potentially useful treatment for AD. Phospholipids such as phosphatidlserine (PS) and phosphatidylcholine (PC) have been reported to modulate the immune function of phagocytes. In addition, PS has been reported to be a nootropics that can be used as nonprescription memory or cognitive enhancers. We therefore evaluated the effects of liposomes, which comprise both PS and PC (PS/PC liposomes), on the microglial production of tumor necrosis factor-alpha (TNF-alpha), nitric oxide (NO), and superoxide (O-.(2)-) induced by amyloid beta (A beta) and interferon-gamma (IFN-gamma). Pretreatment of microglia with PS/PC liposomes considerably inhibited the TNF-alpha, NO and O-.(2)- production induced by A beta/IFN-gamma. These results suggest that PS/PC liposomes have both neuroprotective and antioxidative properties through the inhibition of microglial activation, thus supporting the nootropic and antidementia effect of PS. (c) 2007 Elsevier Inc. All rights reserved..
163. Sadayuki Hashioka, Youn Hee Han, Shunsuke Fujii, Takahiro Kato, Akira Monji, Hideo Utsumi, Makoto Sawada, Hiroshi Nakanishi, Shigenobu Kanba, Phospholipids modulate superoxide and nitric oxide production by lipopolysaccharide and phorbol 12-myristate-13-acetate-activated microglia, Neurochemistry International, 10.1016/j.neuint.2006.10.006, 50, 3, 499-506, 2007.02, Microglial activation and inflammatory processes have been implicated in the pathogenesis of a number of neurodegenerative disorders. Recently, peroxynitrite (ONOO-), the reaction product of superoxide ({radical dot}O2-) and nitric oxide (NO) both of which can be generated by activated microglia, has been demonstrated to act as a major mediator in the neurotoxicity induced by activated microglia. On the other hand, phospholipids such as phosphatidylserine (PS) and phosphatidylcholine (PC) have been reported to modulate the immune function of phagocytes. We therefore evaluated the effects of liposomes which comprise both PS and PC (PS/PC liposomes) or PC only (PC liposomes) regarding the production of both {radical dot}O2- and NO by lipopolysaccharide (LPS)/phorbol 12-myristate-13-acetate (PMA)-activated microglia using electron spin resonance (ESR) spin trap technique with a DEPMPO and Griess reaction, respectively. Pretreatment with PS/PC liposomes or PC liposomes considerably inhibited the signal intensity of {radical dot}O2- adduct associated with LPS/PMA-activated microglia in a dose-dependent manner. In addition, pretreatment with PS/PC liposomes also significantly reduced LPS/PMA-induced microglial NO production. In contrast, pretreatment with PC liposomes had no effect on the NO production. These results indicate that PS/PC liposomes can inhibit the microglial production of both NO and {radical dot}O2-, and thus presumably prevent a subsequent formation of ONOO-. Therefore, PS/PC liposomes appear to have both neuroprotective and anti-oxidative properties through the inhibition of microglial activation..
164. Sadayuki Hashioka, Youn-Hee Han, Shunsuke Fujii, Takahiro Kato, Akira Monji, Hideo Utsumi, Makoto Sawada, Hiroshi Nakanishi, Shigenobu Kanba, Phospholipids modulate superoxide and nitric oxide production by lipopolysaccharide and phorbol 12-myristate-13-acetate-activated microglia, NEUROCHEMISTRY INTERNATIONAL, 10.1016/j.neuint.2006.10.006, 50, 3, 499-506, 2007.02, Microglial activation and inflammatory processes have been implicated in the pathogenesis of a number of neurodegenerative disorders. Recently, peroxynitrite (ONOO-), the reaction product of superoxide (O-center dot(2)-) and nitric oxide (NO) both of which can be generated by activated microglia, has been demonstrated to act as a major mediator in the neurotoxicity induced by activated microglia. On the other hand, phospholipids such as phosphatidylserine (PS) and phosphatidy1choline (PC) have been reported to modulate the immune function of phagocytes. We therefore evaluated the effects of liposomes which comprise both PS and PC (PS/PC liposomes) or PC only (PC liposomes) regarding the production of both center dot O-2(-) and NO by lipopolysaccharide (LPS)/phorbol 12-myristate- 13-acetate (PMA)-activated microglia using electron spin resonance (ESR) spin trap technique with a DEPMPO and Griess reaction, respectively. Pretreatment with PS/PC liposomes or PC liposomes considerably inhibited the signal intensity of O-center dot(2)- adduct associated with LPS/PMA-activated rnicroglia in a dose-dependent manner. In addition, pretreatment with PS/PC liposomes also significantly reduced LPS/PMA-induced microglial NO production. In contrast, pretreatment with PC liposomes had no effect on the NO production. These results indicate that PS/PC liposomes can inhibit the microglial production of both NO and center dot O-2(-), and thus presumably prevent a subsequent formation of ONOO-. Therefore, PS/PC liposomes appear to have both neuroprotective and anti-oxidative properties through the inhibition of micro-lial activation. (c) 2006 Elsevier Ltd. All rights reserved..
165. Takahiro Kato, Significance of cross-cultural experience for young psychiatrists--learning from "The Joint Workshop for Psychiatric Residents of Korea and Japan", Seishin shinkeigaku zasshi = Psychiatria et neurologia Japonica, 108, 11, 1194-1200, 2006.11, Korea and Japan are geographically very close, and a variety of cultural exchanges have taken place in recorded history. However, Korea and Japan have been enriched by the influence of Western cultures along with modernization, and mutual exchanges between the two countries have thus decreased in numerous fields including mental health and psychiatry. Prof. Masahisa Nishizono and Prof. Byun-Kun Min, who are leaders in the field of psychiatry in both Japan and Korea, have established "The Joint Workshop for Psychiatric Residents of Korea and Japan", which has been held alternately in Fukuoka or Seoul every summer since 2000. This Joint Workshop provides young psychiatrists with real experiences and many opportunities to learn about transcultural psychiatry regarding both countries. The participants are able to obtain a better mutual understanding of psychiatric epidemiology, recent developments in biological psychiatry while also learning about different concepts regarding the stigma of mental disorders. All participants could also increase their knowledge about the traditional culture and social changes related to the field of psychiatry in both countries. The workshop has helped to build friendship and mutual cooperation between both nations. Contemporary societies are continually becoming more and more diversified and complicated. For young psychiatrists who have to treat patients with modern difficulties and various complicated problems, such cross-cultural experiences may be useful for establishing potentially new and effective treatments for such patients. Psychiatrists and mental health experts have tried to reduce of stigma and discrimination against people with mental disorders, but even today such stigma and discrimination continues to strongly exist. The author thinks that such cross-cultural experiences by the psychiatrists themselves may help to reduce such notions. The author would like to explore the role of cross-cultural experiences in the field of psychiatry..
166. Tomoyuki Ohara, Akira Monji, Toshiaki Onitsuka, Toshihiko Maekawa, Yoji Hirano, Shogo Hirano, Sadayuki Hashioka, Takahiro Kato, Ichiro Yoshida, Shigenobu Kanba, Interictal psychosis after stroke with forced normalization [6], Journal of Neuropsychiatry and Clinical Neurosciences, 10.1176/jnp.2006.18.4.557, 18, 4, 557-559, 2006.10.
167. Interictal psychosis after stroke with forced normalization..
168. Hideki Horikawa, Akira Monji, Masayuki Sasaki, Toshihiko Maekawa, Toshiaki Onitsuka, Yoko Nitazaka, Yoji Hirano, Shougo Hirano, Sadayuki Hashioka, Takahiro Kato, Ichiro Yoshida, Shigenobu Kanba, Different SPECT findings before and after Capgras' syndrome in interictal psychosis, Epilepsy and Behavior, 10.1016/j.yebeh.2006.04.016, 9, 1, 189-192, 2006.08, We herein report a case of Capgras' syndrome observed in interictal psychosis in which the single-photon emission computed tomography (SPECT) findings before and after the appearance of the psychotic symptoms differed. SPECT with 99mTc-hexamethyl propyleneamine oxine (HMPAO) revealed worsening of hypoperfusion in the entire right hemisphere after onset of the psychotic symptoms. The enhanced hypoperfusion demonstrated by SPECT in the present case seems to indicate a right interhemispheric disconnection resulting in the occurrence of Capgras' syndrome..
169. Takahiro Kato, Eisuke Hanada, Kyoko Takano, Yasuaki Antoku, Yoshiaki Nose, A question and answer E-mail system for responding to query from the general public with which the system manager can identify delayed replies, Journal of Medical Systems, 10.1023/A:1005476928236, 24, 1, 21-28, 2000.02, We constructed a question and answer system for direct delivery of E- mail queries from the general public to the proper hospital representative and with which the system administrator can monitor E-mail replies. The system consists of two subsystems; one is an E-mail questionnaire sub-system that automatically delivers E-mail queries to the proper person and an E-mail reply monitor sub-system with which the system administrator can monitor the E-mail replies. The monitor system compares the origin address of the E-mail reply and the destination address on a questionnaire filled out at the time the query is made. In a test of the system, 56 queries were received in 31 days, with 37 replied to. The interval from receipt of an E-mail query to reply was calculated. Nineteen replies were submitted within 2 days..
170. Hideki Horikawa, Akira Monji, Masayuki Sasaki, Toshihiko Maekawa, Toshiaki Onitsuka, Yoko Nitazaka, Yoji Hirano, Shougo Hirano, Sadayuki Hashioka, Takahiro Kato, Ichiro Yoshida, Shigenobu Kanba, Different SPECT findings before and after Capgras' syndrome in interictal psychosis, Epilepsy and Behavior, 10.1016/j.yebeh.2006.04.016, 9, 1, 189-192, 2006.08, We herein report a case of Capgras' syndrome observed in interictal psychosis in which the single-photon emission computed tomography (SPECT) findings before and after the appearance of the psychotic symptoms differed. SPECT with 99mTc-hexamethyl propyleneamine oxine (HMPAO) revealed worsening of hypoperfusion in the entire right hemisphere after onset of the psychotic symptoms. The enhanced hypoperfusion demonstrated by SPECT in the present case seems to indicate a right interhemispheric disconnection resulting in the occurrence of Capgras' syndrome. © 2006 Elsevier Inc. All rights reserved..
171. Takahiro Kato, Eisuke Hanada, Kyoko Takano, Yasuaki Antoku, Yoshiaki Nose, A question and answer E-mail system for responding to query from the general public with which the system manager can identify delayed replies, Journal of Medical Systems, 10.1023/A:1005476928236, 24, 1, 21-28, 2000.02, We constructed a question and answer system for direct delivery of E- mail queries from the general public to the proper hospital representative and with which the system administrator can monitor E-mail replies. The system consists of two subsystems
one is an E-mail questionnaire sub-system that automatically delivers E-mail queries to the proper person and an E-mail reply monitor sub-system with which the system administrator can monitor the E-mail replies. The monitor system compares the origin address of the E-mail reply and the destination address on a questionnaire filled out at the time the query is made. In a test of the system, 56 queries were received in 31 days, with 37 replied to. The interval from receipt of an E-mail query to reply was calculated. Nineteen replies were submitted within 2 days..