||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.
||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..
||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.
||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..
||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.
||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.
||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..
||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.
||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..
||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..
||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..
||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。.
||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..
||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..
||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。.
||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..
||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.
||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.