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Master

Affiliation (Master)

  • Hokkaido University Hospital　Division of Neural and Sensory Organs　Department of Psychiatry

Affiliation (Master)

  • Hokkaido University Hospital　Division of Neural and Sensory Organs　Department of Psychiatry

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Profile and Settings

Profile and Settings

  • Profile

    I graduated from Nippon Medical School in 1987, and in 1992 I joined Cornell Medical School, Westchester division as a visiting fellow. In 1993, I embarked on a residency training program in psychiatry at Montefiore Medical Center/Albert Einstein College of Medicine, which I completed in 1997. I was then appointed Chief Resident and was charged with supervising the psychiatry residents. Subsequently, I became a research fellow, during which time I conducted clinical research and provided patient care at the Bronx Psychiatric Center.
    My clinical research involved the evaluation of atypical antipsychotic medications in patients with schizophrenia. This work was conducted as part of a wide-ranging multi-site psychopharmacology study. After completing my fellowship, I became a faculty member in the department. As a fellow, I pursued training in molecular genetics techniques and statistics. A number of important papers came out of our Program of Behavioral Genetics Program, including work on a genetic factor relating to violence in schizophrenia and ultra rapid cycling bipolar disorder. Over the years, I received research grants from the American Psychiatric Association and NARSAD that allowed me to work for the Basic Research Division in the Department of Psychiatry, where I focused particularly on identifying a genetic locus on chromosome 22q11 in multiple psychiatric disorders and neurodevelopmental disorders. I also played a major role in providing psychiatric care for the Japanese community in New York by serving as a psychiatric consultant to the Japanese Consul General in New York. I also served as a consultant to the Japan Education Center to help Japanese children with mental health problems.
    In 2005, I returned to Nippon Medical School, Japan, where I established a child and adolescent clinic and focused on mood disorder and neurodevelopmental disorder. In 2014, I moved to Hokkaido University and started a new Department of Child and Adolescent Psychiatry.

  • Name (Japanese)

    Saito

  • Name (Kana)

    Takuya

  • Name

    201401081965830926

Alternate Names

Achievement

Research Interests

  • 児童思春期精神医学   児童精神医学   自己治癒力   総合失調症   TNF-α   質的評価   統合失調症   面接分析   指標   PET   癒し   HPS   模擬患者   免疫   笑い   患者   エビデンス   分子イメージング   ドパミン   D2受容体   

Research Areas

  • Life sciences / Psychiatry / child and adolescent psychiatry
  • Life sciences / Psychiatry
  • Life sciences / Healthcare management, medical sociology

Research Experience

  • 2014/04 - Today Hokkaido University Graduate School of Medicine
  • 2005/04 - 2014/03 Nippon Medical School Medical School

Education

  • 1981/04 - 1987/03  Nippon Medical School

Published Papers

  • Noa Tsujii, Takashi Okada, Masahide Usami, Hidenori Kuwabara, Junichi Fujita, Hideki Negoro, Junzo Iida, Yumi Aoki, Yoshikazu Takaesu, Takuya Saito
    Psychiatry and Clinical Neurosciences Reports 1 (4) 2769-2558 2022/12
  • Hidenori Yamasue, Masaki Kojima, Hitoshi Kuwabara, Miho Kuroda, Kaori Matsumoto, Chieko Kanai, Naoko Inada, Keiho Owada, Keiko Ochi, Nobutaka Ono, Seico Benner, Tomoyasu Wakuda, Yosuke Kameno, Jun Inoue, Taeko Harada, Kenji Tsuchiya, Kazuo Umemura, Aya Yamauchi, Nanayo Ogawa, Itaru Kushima, Norio Ozaki, Satoshi Suyama, Takuya Saito, Yukari Uemura, Junko Hamada, Yukiko Kano, Nami Honda, Saya Kikuchi, Moe Seto, Hiroaki Tomita, Noriko Miyoshi, Megumi Matsumoto, Yuko Kawaguchi, Koji Kanai, Manabu Ikeda, Itta Nakamura, Shuichi Isomura, Yoji Hirano, Toshiaki Onitsuka, Hirotaka Kosaka, Takashi Okada
    Brain : a journal of neurology 145 (2) 490 - 499 2022/04/18 
    Although intranasal oxytocin is expected to be a novel therapy for the core symptoms of autism spectrum disorder, which has currently no approved medication, the efficacy of repeated administrations was inconsistent, suggesting that the optimal dose for a single administration of oxytocin is not optimal for repeated administration. The current double-blind, placebo-controlled, multicentre, crossover trial (ClinicalTrials.gov Identifier: NCT03466671) was aimed to test the effect of TTA-121, a new formulation of intranasal oxytocin spray with an enhanced bioavailability (3.6 times higher than Syntocinon® spray, as assessed by area under the concentration-time curve in rabbit brains), which enabled us to test a wide range of multiple doses, on autism spectrum disorder core symptoms and to determine the dose-response relationship. Four-week administrations of TTA-121, at low dose once per day (3 U/day), low dose twice per day (6 U/day), high dose once per day (10 U/day), or high dose twice per day (20 U/day), and 4-week placebo were administered in a crossover manner. The primary outcome was the mean difference in the reciprocity score (range: 0-14, higher values represent worse outcomes) on the Autism Diagnostic Observation Schedule between the baseline and end point of each administration period. This trial with two administration periods and eight groups was conducted at seven university hospitals in Japan, enrolling adult males with high-functioning autism spectrum disorder. Enrolment began from June 2018 and ended December 2019. Follow-up ended March 2020. Of 109 males with high-functioning autism spectrum disorder who were randomized, 103 completed the trial. The smallest P-value, judged as the dose-response relationship, was the contrast with the peak at TTA-121 6 U/day, with inverted U-shape for both the full analysis set (P = 0.182) and per protocol set (P = 0.073). The Autism Diagnostic Observation Schedule reciprocity score, the primary outcome, was reduced in the TTA-121 6 U/day administration period compared with the placebo (full analysis set: P = 0.118, mean difference = -0.5; 95% CI: -1.1 to 0.1; per protocol set: P = 0.012, mean difference = -0.8; 95% CI: -1.3 to -0.2). The per protocol set was the analysis target population, consisting of all full analysis set participants except those who deviated from the protocol. Most dropouts from the full analysis set to the per protocol set occurred because of poor adherence to the test drug (9 of 12 in the first period and 8 of 15 in the second period). None of the secondary clinical and behavioural outcomes were significantly improved with the TTA-121 compared with the placebo in the full analysis set. A novel intranasal spray of oxytocin with enhanced bioavailability enabled us to test a wide range of multiple doses, revealing an inverted U-shape dose-response curve, with the peak at a dose that was lower than expected from previous studies. The efficacy of TTA-121 shown in the current exploratory study should be verified in a future large-scale, parallel-group trial.
  • 恐怖記憶の分子・生理学的基盤の解明とPTSDの治療開発 PTSD治療におけるmemantineの効果と意義
    金 吉晴, 堀 弘明, 伊藤 真利子, 松井 三枝, 加茂 登志子, 斎藤 卓弥, 西松 能子, 鬼頭 諭, 喜田 聡
    精神神経学雑誌 (公社)日本精神神経学会 124 (4付録) S - 295 0033-2658 2022/04 [Not refereed]
  • Takuya Saito, Mitsuhiro Ishida, Atsushi Nishiyori, Toshimitsu Ochiai, Hideaki Katagiri, Hideo Matsumoto
    Journal of child and adolescent psychopharmacology 32 (3) 132 - 142 2022/04 
    Objective: The goal of this study was to evaluate the efficacy and safety of duloxetine in children and adolescents (9-17 years of age) with major depressive disorder (MDD) in Japan. Methods: This study consists of two clinical trials. First, a 6-week, randomized double-blind placebo-controlled clinical trial (RCT) was conducted. The primary endpoint of RCT was the change in Children's Depression Rating Scale-Revised (CDRS-R) total scores from baseline. Following RCT, an open-label long-term extension trial (OLE) was conducted to investigate the longer-term safety of duloxetine for ∼1 year. Results: In RCT, CDRS-R total score changes from baseline to 6 weeks after the start of administration (primary endpoint) were -21.03 in the duloxetine group (n = 74) and -22.42 in the placebo group (n = 74). No significant difference was observed in the primary endpoint between the groups (p = 0.5587). In addition, no significant difference was observed in secondary endpoints such as CDRS-R response rates. The proportion of patients with ≥1 treatment-emergent adverse event (TEAE) in RCT was significantly higher in the duloxetine group (78.7%) than in the placebo group (62.2%), and most were mild or moderate in severity. Changes in CDRS-R total scores during OLE, in consecutive patients from the duloxetine group in RCT (n = 63), or placebo group (n = 59) in RCT, and newly enrolled patients (n = 28), were -12.1, -11.3, and -17.8, respectively. The proportion of patients with ≥1 TEAE in OLE was 90.5%, 88.1%, and 89.3% in the respective groups, and most of them were mild or moderate in severity. Conclusions: Duloxetine did not show superiority to placebo in efficacy in children and adolescents with MDD in Japan. Overall reported TEAEs were consistent with the currently available duloxetine safety profile and no new safety finding was observed in the two clinical trials.
  • Takuya Saito, Yohei Hyodo, Reiko Sakaguchi, Hiroshi Nakamura, Jun Ishigooka
    Journal of child and adolescent psychopharmacology 32 (1) 24 - 35 2022/02 
    Objectives: To evaluate the long-term efficacy and safety/tolerability of oral blonanserin in adolescents with schizophrenia (Study registration number: JapicCTI-111725). Methods: This 52-week, multicenter, open-label extension study enrolled adolescent patients with schizophrenia who opted to enter in this study after the completion of the preceding placebo-controlled study. Blonanserin tablet was orally administered twice daily, after morning and evening meals, for 52 weeks using dose-titration method within a range between 4 and 24 mg/day. The primary end point was the change from baseline to the end of the study in the Positive and Negative Syndrome Scale (PANSS) total score. Safety/tolerability was assessed by the incidence and severity of adverse events. Results: Of 117 patients who completed the preceding placebo-controlled study, 109 entered this extension study and 43 (39.4%) of them discontinued the study treatment. The safety analysis set comprised 106 patients who received the study drug at least once, including 36 and 70 patients treated with placebo (DB-placebo group) and blonanserin tablet (DB-blonanserin group), respectively, in the placebo-controlled study. At the last assessment, the mean change in PANSS total score overall [mean (standard deviation)] was -24.9 (20.76) from the baseline of the placebo-controlled study, which was similar in the DB-placebo and DB-blonanserin groups. The overall incidence of adverse events was 90.6%, and most of them were mild or moderate in severity, with similar incidence of extrapyramidal symptoms (38.7%) to that in adults receiving long-term blonanserin oral tablet treatment and minimal change in weight and metabolic parameters. Conclusions: This long-term extension study showed that 52 weeks of oral blonanserin treatment improved or stabilized psychiatric symptoms in patients with adolescent schizophrenia. There were no major issues with the safety or tolerability of blonanserin administration in this study. Considering relatively less adverse effects on weight increase and metabolic parameters, blonanserin is expected to be a safe/tolerable treatment option for adolescent schizophrenia that can be used seamlessly from adolescence to adulthood.
  • Takuya Saito, Saori Sugimoto, Reiko Sakaguchi, Hiroshi Nakamura, Jun Ishigooka
    Journal of child and adolescent psychopharmacology 32 (1) 12 - 23 2022/02 
    Objectives: To evaluate the short-term efficacy and safety of blonanserin in adolescents with schizophrenia. Methods: This 6-week multicenter, double-blind, randomized, placebo-controlled study investigated fixed-dose blonanserin (8 or 16 mg/day) in patients 12-18 years of age diagnosed with schizophrenia, as indicated by a Positive and Negative Syndrome Scale (PANSS) total score of 60-120 and a Clinical Global Impressions-Severity score of ≥3. The primary endpoint was change from baseline to week 6 in the PANSS total score, using a mixed model for repeated measures analysis. Safety was assessed by the incidence and severity of adverse events (AEs). Results: Among 151 randomized patients, 150 were included in the primary analysis population. Demographic and clinical characteristics were similar across groups at baseline. The rate of study discontinuation was 14.9%, 23.5%, and 28.3% in patients administered with placebo, blonanserin 8 mg/day, and blonanserin 16 mg/day, respectively. The least-squares mean change (95% confidence interval [CI]) from baseline to week 6 in PANSS total score was -10.6 (-16.10 to -5.10), -15.3 (-20.80 to -9.86), and -20.5 (-25.89 to -15.16) in patients administered placebo, 8 mg/day blonanserin, and 16 mg/day blonanserin, respectively. The 16-mg/day blonanserin group showed significantly greater reduction in the PANSS total score than the placebo group (least-squares mean difference [95% CI]: -9.9 [-17.61 to -2.25], p = 0.012, effect size: 0.538), although the 8-mg/day group showed no significant difference. The incidence of AEs such as akathisia, somnolence, and hyperprolactinemia was higher in the blonanserin groups than in the placebo group. AEs associated with blonanserin were generally mild and were consistent with its known profile in adults with schizophrenia. Conclusions: Blonanserin achieved a sufficient efficacy in adolescent patients, and the safety profile was similar to that in adults, which suggests that blonanserin may be a safe treatment option for adolescents with schizophrenia. Study registration number: Japic CTI-111724.
  • Sachiko Itoh, Keiko Yamazaki, Satoshi Suyama, Atsuko Ikeda-Araki, Chihiro Miyashita, Yu Ait Bamai, Sumitaka Kobayashi, Hideyuki Masuda, Takeshi Yamaguchi, Houman Goudarzi, Emiko Okada, Ikuko Kashino, Takuya Saito, Reiko Kishi
    Environment international 159 107026 - 107026 2022/01/15 
    BACKGROUND: Disruption of thyroid hormone (TH) levels during pregnancy contributes to attention deficit hyperactivity disorder (ADHD). Exposure to perfluoroalkyl substances (PFAS) during gestation may affect levels of maternal and neonatal TH; however, little is known about the effect of PFAS on ADHD mediated by TH. OBJECTIVES: We investigated the impact of maternal PFAS exposure on children's ADHD symptoms with the mediating effect of TH. METHODS: In a prospective birth cohort (the Hokkaido study), we included 770 mother-child pairs recruited between 2002 and 2005 for whom both prenatal maternal and cord blood samples were available. Eleven PFAS were measured in maternal serum obtained at 28-32 weeks of gestation using ultra-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry. TH and thyroid antibody, including thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb) were measured in maternal blood during early pregnancy (median 11 gestational weeks) and in cord blood at birth. ADHD symptoms in the children at 8 years of age were rated by their parents using the ADHD-Rating Scale (ADHD-RS). The cut-off value was set at the 80th percentile for each sex. RESULTS: Significant inverse associations were found between some PFAS in maternal serum and ADHD symptoms among first-born children. Assuming causality, we found only one significant association: maternal FT4 mediated 17.6% of the estimated effect of perfluoroundecanoic acid exposure on hyperactivity-impulsivity among first-born children. DISCUSSION: Higher PFAS levels in maternal serum during pregnancy were associated with lower risks of ADHD symptoms at 8 years of age. The association was stronger among first-born children in relation to hyperactivity-impulsivity than with regard to inattention. There was little mediating role of TH during pregnancy in the association between maternal exposure to PFAS and reduced ADHD symptoms at 8 years of age.
  • Hayato Watanabe, Atsushi Shimojo, Kazuyori Yagyu, Tsuyoshi Sonehara, Kazuyoshi Takano, Jared Boasen, Hideaki Shiraishi, Koichi Yokosawa, Takuya Saito
    PloS one 17 (6) e0270090  2022 
    Communication is one of the most important abilities in human society, which makes clarification of brain functions that underlie communication of great importance to cognitive neuroscience. To investigate the rapidly changing cortical-level brain activity underlying communication, a hyperscanning system with both high temporal and spatial resolution is extremely desirable. The modality of magnetoencephalography (MEG) would be ideal, but MEG hyperscanning systems suitable for communication studies remain rare. Here, we report the establishment of an MEG hyperscanning system that is optimized for natural, real-time, face-to-face communication between two adults in sitting positions. Two MEG systems, which are installed 500m away from each other, were directly connected with fiber optic cables. The number of intermediate devices was minimized, enabling transmission of trigger and auditory signals with almost no delay (1.95-3.90 μs and 3 ms, respectively). Additionally, video signals were transmitted at the lowest latency ever reported (60-100 ms). We furthermore verified the function of an auditory delay line to synchronize the audio with the video signals. This system is thus optimized for natural face-to-face communication, and additionally, music-based communication which requires higher temporal accuracy is also possible via audio-only transmission. Owing to the high temporal and spatial resolution of MEG, our system offers a unique advantage over existing hyperscanning modalities of EEG, fNIRS, or fMRI. It provides novel neuroscientific methodology to investigate communication and other forms of social interaction, and could potentially aid in the development of novel medications or interventions for communication disorders.
  • Nano Yoneta, Hayato Watanabe, Atsushi Shimojo, Kazuyoshi Takano, Takuya Saito, Kazuyori Yagyu, Hideaki Shiraishi, Koichi Yokosawa, Jared Boasen
    Frontiers in neuroscience 16 790057 - 790057 2022 
    Auditory communication is an essential form of human social interaction. However, the intra-brain cortical-oscillatory drivers of auditory communication exchange remain relatively unexplored. We used improvisational music performance to simulate and capture the creativity and turn-taking dynamics of natural auditory communication. Using magnetoencephalography (MEG) hyperscanning in musicians, we targeted brain activity during periods of music communication imagery, and separately analyzed theta (5-7 Hz), alpha (8-13 Hz), and beta (15-29 Hz) source-level activity using a within-subjects, two-factor approach which considered the assigned social role of the subject (leader or follower) and whether communication responses were improvisational (yes or no). Theta activity related to improvisational communication and social role significantly interacted in the left isthmus cingulate cortex. Social role was furthermore differentiated by pronounced occipital alpha and beta amplitude increases suggestive of working memory retention engagement in Followers but not Leaders. The results offer compelling evidence for both musical and social neuroscience that the cognitive strategies, and correspondingly the memory and attention-associated oscillatory brain activities of interlocutors during communication differs according to their social role/hierarchy, thereby indicating that social role/hierarchy needs to be controlled for in social neuroscience research.
  • Kazuyori Yagyu, Ryusaku Hashimoto, Atsushi Shimojo, Michiru Iwata, Keitaro Sueda, Ayumi Seki, Hideaki Shiraishi, Takuya Saito
    Brain & development 43 (9) 893 - 903 2021/10 
    BACKGROUND: Dyslexia is a neurodevelopmental disorder which occurs in childhood but continues to influence academic and occupational function in adulthood. Recently, a Japanese dyslexia questionnaire and diagnostic procedure was established for primary school children. However, there is currently no procedure for the diagnosis or screening of dyslexia in individuals at or above junior high school age; accordingly, we aimed to develop a questionnaire to screen for reading difficulties in those individuals. METHODS: A questionnaire with various candidate items was developed from two English questionnaires, one Japanese questionnaire, and newly devised items focusing on the Japanese writing system and the most appropriate 28 items were selected. In total, 462 adults and 127 junior high to high school students were enrolled. Of those, 191 participants also took part in reading tests. After the exploratory factor analysis, reliability and validity were evaluated using the above control participants and 12 adolescents with dyslexia. RESULTS: The questionnaire included three factors, i.e., silent reading sub-scale (four items), writing sub-scale (four items), and aloud reading sub-scale (three items). Five were newly devised items focusing on the Japanese writing system. Cronbach's alphas of the three factors were 0.706, 0.638, and 0.568, respectively, and the interclass correlation coefficients (2,1) were 0.743, 0.609, and 0.695, respectively. The silent reading and aloud reading sub-scales were positively correlated with word, non-word, and passage reading time. DISCUSSION: The newly developed questionnaire correlated well with actual reading performance and may be used to screen reading difficulty in Japanese individuals at or above junior high school age.
  • Hyperscanningと脳活動 脳磁図を用いたコミュニケーション脳科学
    柳生 一自, 渡辺 隼人, 高野 一義, 下條 暁司, 白石 秀明, 横澤 宏一, 齊藤 卓弥
    精神神経学雑誌 (公社)日本精神神経学会 (2021特別号) S490 - S490 0033-2658 2021/09
  • ハイパースキャニングによる社会脳機能計測 Dual MEGを用いたコミュニケーション脳科学の可能性
    柳生 一自, 渡辺 隼人, 高野 一義, 下條 暁司, 白石 秀明, 横澤 宏一, 齊藤 卓弥
    日本生体磁気学会誌 日本生体磁気学会 34 (1) 108 - 108 0915-0374 2021
  • Hiroaki Hori, Mariko Itoh, Mie Matsui, Toshiko Kamo, Takuya Saito, Yoshiko Nishimatsu, Satoshi Kito, Satoshi Kida, Yoshiharu Kim
    European Journal of Psychotraumatology 12 (1) 1859821 - 1859821 2000-8198 2021/01/15 
    Background: Currently, there is a paucity of pharmacological treatment options for posttraumatic stress disorder (PTSD), and the development of a novel pharmacotherapeutic approach has become a matter of great interest. Objective: We conducted a 12-week open-label clinical trial to examine the efficacy and safety of memantine, an N-methyl-D-aspartate receptor antagonist, in the treatment of civilian PTSD. Method: Thirteen adult patients with DSM-IV PTSD, all civilian women, were enrolled. They were monitored at an ambulatory care facility every week until 4 weeks and then every 4 weeks until 12 weeks. Memantine was added to each patient's current medication, with the initial dosage of 5 mg/day and then titrated. Concomitant medications were essentially kept unchanged during the trial. The primary outcome was PTSD diagnosis and severity assessed with the Posttraumatic Diagnostic Scale (PDS). Results: Of the 13 cases, one dropped out and two were discarded due to the protocol deviation, and the analysis was done for the remaining 10. Mean PDS total scores decreased from 32.3 ± 9.7 at baseline to 12.2 ± 7.9 at endpoint, which was statistically significant with a large effect (paired t-test: p = .002, d = 1.35); intrusion, avoidance, hyperarousal symptoms were all significantly improved from baseline to endpoint. Six patients no longer fulfilled the diagnostic criteria of PTSD at endpoint. Some adverse, but not serious, effects possibly related to memantine were observed, including sleep problems, sleepiness, sedation, weight change and hypotension. Conclusions: Memantine significantly reduced PTSD symptoms in civilian female PTSD patients and the drug was well tolerated. Future randomized controlled trials are necessary to verify the efficacy and safety of memantine in the treatment of PTSD.
  • Takuya Saito, Yushiro Yamashita, Akemi Tomoda, Takashi Okada, Hideo Umeuchi, Saki Iwamori, Satoru Shinoda, Akiko Mizuno-Yasuhira, Hidetoshi Urano, Izumi Nishino, Kazuhiko Saito
    BMC psychiatry 20 (1) 530 - 530 2020/11/10 
    BACKGROUND: Asverin® (tipepidine hibenzate) has been used as an antitussive for > 50 years in Japan. Studies revealed that tipepidine modulates monoamine levels, by inhibiting G-protein-activated inwardly rectifying potassium (GIRK) channels, expecting the potential therapeutic effects of tipepidine for attention-deficit/hyperactivity disorder (ADHD) in recent years. In this study, TS-141, a sustained-release tablet of tipepidine, was developed for the treatment of ADHD through a drug repositioning approach. METHODS: The sustained-release profile of TS-141 in healthy adults was investigated, and tipepidine exposure in the plasma after the TS-141 administration was compared to that of Asverin in the phase I study. Phase II study was conducted to examine the effects of TS-141 30 (once a day), 60 (once a day), 120 mg (60 mg twice a day), or placebo, that is within the exposure in the maximum dosage of Asverin, in children and adolescents with ADHD, and was designed as an 8-week treatment, randomized, parallel group, double-blind, placebo-controlled trial recruiting 6-17-year-old children and adolescents diagnosed with ADHD. A total of 216 patients were randomized according to the CYP2D6 phenotype. The primary end-point was ADHD Rating Scale IV-J changes. Furthermore, effects of CYP2D6 phenotype on the efficacy in the subgroup analysis were investigated. RESULTS: TS-141 had the sustained-release profile, and the CYP2D6 phenotype had effects on the plasma exposure of tipepidine. ADHD RS-IV-J scores in all TS-141 dosages decreased from their baseline scores; however, no significant difference was observed in ADHD RS-IV-J score changes between the placebo and TS-141-administered groups. In patients with intermediate metabolizer CYP2D6, ADHD RS-IV-J score changes in the 120 mg group tended to be larger than that in the placebo group. CONCLUSIONS: ADHD RS-IV-J changes on TS-141 may depend on the interaction between the TS-141 dose and CYP2D6 phenotype, suggesting that further clinical trials should be conducted with careful consideration of polymorphism. Drug repositioning approach of TS-141 was attempted at the same dose as that of antitussive; however, dose setting according to the indication was necessary. TRIAL REGISTRATION: Phase I study: JapicCTI-205235 (Registered 25 March 2020), Phase II study: JapicCTI-163244 (Registered 9 May 2016), https://www.clinicaltrials.jp/cti-user/trial/Show.jsp.
  • Masaki Adachi, Michio Takahashi, Tomoya Hirota, Hiroki Shinkawa, Hiroyuki Mori, Takuya Saito, Kazuhiko Nakamura
    Psychiatry and Clinical Neurosciences 74 (11) 628 - 629 1323-1316 2020/11/01
  • 柳生 一自, 渡辺 隼人, 高野 一義, 下條 暁司, 白石 秀明, 横澤 宏一, 齊藤 卓弥
    臨床神経生理学 (一社)日本臨床神経生理学会 48 (5) 440 - 440 1345-7101 2020/10
  • Satoshi Suyama, Kazuyori Yagyu, Atsuko Araki, Chihiro Miyashita, Sachiko Itoh, Machiko Minatoya, Keiko Yamazaki, Naomi Tamura, Akio Nakai, Takuya Saito, Reiko Kishi
    Pediatrics International 62 (10) 1177 - 1183 1328-8067 2020/10/01 
    BACKGROUND: Motor coordination problems (MCP) in children can sometimes be diagnosed as developmental coordination disorder. Early intervention for developmental coordination disorder is necessary because it often continues into adolescence, causing mental and physical complications. Few studies have investigated the prevalence of childhood MCP in the Japanese population, examining the risk factors for MCP. We therefore investigated the prenatal factors associated with MCP in preschool-age children. METHODS: This study was based on a prospective cohort study, the Hokkaido Study on Environment and Children's Health. Mothers of 4,851 children who reached the age of 5 years within the study-period received questionnaires, including the Japanese version of the Developmental Coordination Disorder Questionnaire (DCDQ-J). We examined the risk factors associated with MCP using logistic regression analysis. RESULTS: Of 3,402 returned DCDQ-J questionnaires, 3,369 were answered completely. From the 3,369 children, we categorized having MCP by using two cut-off scores: that of the DCDQ'07 and the cut-off at the 5th percentile of a total DCDQ-J score. Comparing children with and without MCP, we found significant differences in the education level of the mothers, annual household income during pregnancy, maternal alcohol consumption and smoking during pregnancy, and sex and age of the children at the time of completing the DCDQ-J by both categorizations. Adjusted logistic regression analysis revealed that maternal smoking during the first trimester of pregnancy and male sex were significantly associated with MCP. CONCLUSIONS: Our results suggest that maternal smoking during pregnancy is the main factor associated with MCP in preschool-age children.
  • Kazuyoshi Takano, Hayato Watanabe, Kazuyori Yagyu, Atsushi Shimojo, Jared Boasen, Yui Murakami, Hideaki Shiraishi, Koichi Yokosawa, Takuya Saito
    Proceedings of the Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBS 2020-July 2893 - 2896 1557-170X 2020/07 
    Face to face communication is interactive, and involves continuous feedforward and feedback of information, thoughts, and feelings to the opposite party. To accurately assess the neural processing underlying these interactions, synchronous and simultaneous recording of the brain activity from both parties is needed, a method known as hyperscanning. Here, we investigated the neural processing underlying nonverbal face-to-face communication using a magnetoencephalographic (MEG) hyperscanning system, comprising two fiber optically connected MEGs. Eight pairs of subjects participated. Each individual in each pair viewed a combined 80 randomized 20 s trials of 40 real-time and 40 recorded (hereafter, real and simulated, respectively) videos of the opposite party's face. Non-verbal communication through actions such as gaze, eye blinks, and facial expression was intrinsically only possible during real videos. After each trial, subjects individually subjectively discriminated whether the viewed video was real or simulated. Overall subjective discrimination accuracies were slightly but significantly above chance level. Statistical analysis of brain activity revealed a significant three way interaction between theta-band rhythm amplitude, video type, and subjective discrimination response in the right frontal cortex. Additionally, when subjects responded that videos were simulated, theta activity was significantly lower for real videos compared with simulated videos (p = 0.01). This result not only demonstrates the importance of right frontal theta activity during non-verbal communication, but also indicates the existence of unconscious, semi-automated neural processing during non-verbal communication that underlies one's ability to subjectively discriminate whether or not the opposite party is real.
  • Noa Tsujii, Jakashi Okada, Masahide Usami, Hidenori Kuwabara, Junichi Fujita, Hideki Negoro, Michiyo Kavwamura, Junzo Lida, Fand Takuya Saito
    Journal of Clinical Psychiatry 81 (3) E1 - E11 0160-6689 2020/06 
    OBJECTIVE: This study aimed to compare the effect of continuing and discontinuing medications on quality of life of patients with attention-deficit/hyperactivity disorder (ADHD). DATA SOURCES: PubMed, Cochrane Library, and Embase databases were searched using generic terms for ADHD, discontinuing, continuing, pharmacotherapy, and randomized controlled trials without date or language restrictions. STUDY SELECTION: Of the 3,672 screened studies, 9 met the predefined inclusion criteria on patients with ADHD; 5 of these 9 studies reporting on 1,463 patients (children and adolescents, n = 894; adults, n = 569) measured quality of life and were included in this meta-analysis. Only randomized, double-blind, placebo-controlled withdrawal trials of ADHD medications were included. DATA EXTRACTION: Data were independently extracted according to the Cochrane Handbook for Systematic Reviews of Interventions. Analyses were based on random-effects models. RESULTS: Compared with continuing medications, discontinuing them significantly worsened quality of life score in patients with ADHD (standardized mean difference [SMD] = 0.19; 95% CI, 0.08 to 0.30]). Moreover, discontinuing medications worsened this score in children and adolescents with ADHD (SMD = 0.21; 95% CI, 0.06 to 0.36) but not in adults with ADHD (SMD = 0.02; 95% CI, -0.46 to 0.50). CONCLUSIONS: Discontinuing medications was associated with a small but statistically significant decrease in quality of life among children and adolescents with ADHD but not in adults with ADHD. Quality of life can be applied in pharmacologic interventions regarding continuing and discontinuing medication because this concept is related to individuals' appraisal of their situation. Quality of life is an important factor for planning individualized ADHD medication treatment.
  • Takuya Saito, Elin H. Reines, Ioana Florea, Mads K. Dalsgaard
    Journal of Child and Adolescent Psychopharmacology 29 (10) 753 - 763 1044-5463 2019/12 
    Objectives: In Japan, there are currently no approved antidepressant treatments for pediatric patients with depression. This study aimed to estimate the prevalence of depression among adolescents under medical care in Japan, the pharmacological treatments used, and the perceived unmet needs among the medical specialties treating depression in the pediatric population. Methods: The study was conducted in November 2014 as an internet survey among physicians in clinical practice. It included a sample of 731 physicians with the potential to treat adolescent patients with depression and 161 physicians who had treated at least one adolescent with depression with pharmacotherapy in the previous 12 months. Of the sample of 161 treating physicians, 60 were internal medicine specialists, 73 were psychiatrists, and 28 were certified specialists from the Japanese Society of Child and Adolescent Psychiatry, Japanese Society of Psychosomatic Medicine Pediatrics, or Japanese Society of Pediatric Psychiatry and Neurology. The participants completed questionnaires concerning their patient population with depression, drug-treated population, and drugs prescribed. Results: Estimates of prevalence data indicated that there were ∼550,000 adolescent patients with depression in Japan (10% of the patient population with depression) under medical care of different medical specialties; ∼64% of these patients were receiving pharmacotherapy. Pharmacotherapy for adolescents with depression was prescribed mainly by psychiatrists (62% of prescriptions for these patients). The most common first-choice agent was sertraline (23% of respondents) followed by anxiolytics (17%) and fluvoxamine (13%), while antipsychotics were the preferred choice for 7%. Conclusion: The study indicates a high prevalence of depression among adolescents in Japan. These patients are seen by different medical specialties; the use of pharmacotherapy is relatively common and comprises various drug classes, including antidepressants, anxiolytics, and antipsychotics. This study shows that there is a medical need for approved treatments for adolescents with depression in Japan.
  • 北海道胆振東部地震における子どもの心のケア 北海道子どものこころのケアチームの活動報告
    杉山 紗詠子, 才野 均, 宮内 まや, 田原 恵, 氏家 武, 傳田 健三, 田中 康雄, 上田 敏彦, 末田 慶太朗, 立野 佳子, 緑川 由紀, 木下 弘基, 中野 育子, 鹿野 智子, 館農 勝, 南波 江太郎, 花香 真宣, 佐藤 祐基, 齊藤 卓弥, 黒川 新二
    日本児童青年精神医学会総会抄録集 (一社)日本児童青年精神医学会 60回 O15 - 2 2019/12
  • リアルタイムコミュニケーションを計測するためのdual MEGシステムの構成
    渡辺 隼人, 下條 暁司, 柳生 一自, 曽根原 剛志, 白石 秀明, 横澤 宏一, 齊藤 卓弥
    日本生体磁気学会誌 日本生体磁気学会 32 (1) 158 - 159 0915-0374 2019 [Not refereed][Not invited]
  • Yasuyuki Okumura, Masahide Usami, Takashi Okada, Takuya Saito, Hideki Negoro, Noa Tsujii, Junichi Fujita, Junzo Iida
    Journal of Child and Adolescent Psychopharmacology 28 (7) 454 - 462 1044-5463 2018/09 
    OBJECTIVE: We aimed to evaluate glucose and prolactin monitoring in children and adolescents initiating antipsychotic therapy using a nationwide claims database. METHODS: A retrospective 15-month cohort study was conducted using the National Database of Health Insurance Claim Information and Specified Medical Checkups in Japan. Patients aged ≤18 years, who were newly prescribed antipsychotics between April 2014 and March 2015, were followed up for 450 days. Outcomes were the use of glucose and prolactin testing through 15 months after drug initiation (index date) with consideration of persistence with antipsychotic therapy. The incidence proportion of patients monitored was assessed within the following four time windows: baseline (between 30 days before the index date and the index date), at 1-3 months (between 1 and 90 days after the index date), at 4-9 months (between 91 and 270 days after the index date), and at 10-15 months (between 271 and 450 days after the index date). RESULTS: Of 43,608 new users in 6620 medical institutions, the percentage of persistent antipsychotic users was 46.4% at 90 days, 29.7% at 270 days, and 23.8% at 450 days after the index date. The proportion of patients who received monitoring within the baseline period was 13.5% (95% confidence interval [CI], 13.2-13.8) for glucose and 0.6% (95% CI, 0.5-0.6) for prolactin, respectively. The proportion of patients who received glucose monitoring at all time windows decreased to 0.9%. The proportion of patients who received prolactin monitoring by the second time window decreased to 0.1%. CONCLUSIONS: Our study shows that monitoring for glucose and prolactin is infrequent in children and adolescents initiating antipsychotic therapy. Strategies for physicians, patients, and guardians are needed to overcome the barriers in glucose and prolactin monitoring.
  • 渡辺 隼人, 柳生 一自, 下條 暁司, 曽根原 剛志, 品田 大成, 前田 珠希, 白石 秀明, 横澤 宏一, 齊藤 卓弥
    日本生体磁気学会誌 日本生体磁気学会 31 (1) 98 - 99 0915-0374 2018/06 [Not refereed][Not invited]
  • 成人期ADHD症状評価スケールHASCAP(ハスカップ)について
    館農 勝, 中野 育子, 白木 淳子, 館農 幸恵, 金澤 潤一郎, 白石 将毅, 河西 千秋, 氏家 武, 齊藤 卓弥
    精神神経学雑誌 (公社)日本精神神経学会 (2018特別号) S375 - S375 0033-2658 2018/06 [Refereed][Not invited]
  • 市川 宏伸, 齊藤 万比古, 齊藤 卓弥, 仮屋 暢聡, 小平 雅基, 太田 晴久, 岸田 郁子, 三上 克央, 太田 豊作, 姜 昌勲, 小坂 浩隆, 堀内 史枝, 奥津 大樹, 藤原 正和, 岩波 明
    精神医学 = Clinical psychiatry 医学書院 60 (4) 399 - 409 0488-1281 2018/04 [Refereed][Not invited]
  • Masaru Tateno, Takahiko Inagaki, Takuya Saito, Anthony P S Guerrero, Norbert Skokauskas
    Psychiatry investigation 14 (5) 525 - 531 2017/09 
    Japan has been facing a serious shortfall of child and adolescent psychiatric workforce relative to increasing service needs. Likely because of a combination of limited workforce supply and limited trust or perception of effectiveness, mental health services are under-utilized by the educational and child welfare systems. Child and adolescent psychiatry (CAP) has not been a formally established specialty in Japan. The lack of basic structure in the specialty most likely contributes to a lack of training facilities, limited exposure to and interest in the specialty, and hence an inadequate workforce. To date, there exists no standardized training program for CAP in Japan and each training hospital determines its own teaching curriculum and training content. Clinical experience in CAP varies greatly among hospitals. To solve current problems in child and adolescent psychiatry in Japan, we advocate for the development and establishment of a more standardized child and adolescent psychiatry training system that is akin to what exists in the US and that teaches and evaluates according to specific competencies. Through standardizing care and education and ultimately improving workforce, the quality of mental health services can be raised. The tragic and costly consequences of unidentified and untreated mental illness in youth can be avoided by taking timely evidence based actions in partnership with others.
  • 柳生 一自, 齊藤 卓弥
    精神科 (有)科学評論社 31 (2) 131 - 134 1347-4790 2017/08
  • 柳生 一自, 齋藤 卓弥
    最新精神医学 (株)世論時報社 21 (6) 407 - 412 1342-4300 2016/11
  • Noa Tsujii, Takuya Saito, Yuji Izumoto, Masahide Usami, Takashi Okada, Hideki Negoro, Junzo Iida
    Journal of child and adolescent psychopharmacology 26 (7) 642 - 5 2016/09 
    OBJECTIVE: In child and adolescent psychiatry, the off-label prescribing of psychotropic medications is common. The purpose of this study was to examine the experiences of Japanese child and adolescent psychiatrists with off-label prescribing to children and/or adolescents (hereafter referred to as "children") and to identify the factors associated with these experiences. METHODS: A prospective questionnaire was sent to 1628 psychiatrists belonging to the Japanese Society for Child and Adolescent Psychiatry. Stepwise logistic regression analyses were used to determine whether demographic characteristics or categories of psychotropic medications were able to independently predict patient refusals of off-label prescribing. RESULTS: The final sample included 447 psychiatrists, and 93% of the respondents (416/447) had experiences with off-label prescribing to children. In addition, 39.7% of the respondents (165/416) experienced patient refusal of off-label prescribing when they informed the children and/or parents of the prescribing. The most commonly prescribed off-label psychotropic medications were antipsychotics (82.0%). Patient refusal was significantly more frequent when the respondents informed parents (p=0.02) and children (p<0.01) about off-label prescribing than when they did not. A stepwise logistic regression analysis revealed that informing parents (odds ratio [OR], 2.73; 95% confidence interval [CI], 1.09-6.82) or children (OR, 1.70; 95% CI, 1.12-2.58) about off-label prescribing and antidepressant use (OR, 2.98; 95% CI, 1.25-7.10) increased the odds of patient refusal of off-label prescribing; however, prescribers' years in practice decreased the odds (OR, 0.98; 95% CI, 0.96-1). CONCLUSIONS: Off-label prescribing of psychotropic medications is common among child and adolescent psychiatrists in Japan. Furthermore, the psychiatrists' experiences with patient refusal of off-label prescribing were significantly associated with informing the parents/patients about off-label prescribing, particularly with regard to use of antidepressants. Further studies are required to support the development of decision making among clinicians.
  • 成重 竜一郎, 川島 義高, 澤谷 篤
    児童青年精神医学とその近接領域 日本児童青年精神医学会 56 (2) 179 - 189 0289-0968 2015 [Refereed][Not invited]
  • Conners' Adult ADHD Rating Scale(CAARS)日本語版の開発 CAARS自己報告式の信頼性と妥当性の検討
    大西 将史, 染木 史緒, 石井 礼花, 市川 宏伸, 内山 敏, 金澤 潤一郎, 神尾 陽子, 川久保 友紀, 齊藤 万比古, 斉藤 卓弥, 杉山 登志郎, 武田 俊信, 竹林 淳和, 田中 康雄, 根來 秀樹, 松本 英夫, 渡部 京太, 辻井 正次, 森 則夫, 中村 和彦
    日本児童青年精神医学会総会抄録集 (一社)日本児童青年精神医学会 54回 400 - 400 2013/10
  • 自殺未遂者の心理社会的特性と自殺企図手段との関係性に関する検討
    成重 竜一郎, 大高 靖史, 齊藤 卓弥, 大久保 善朗
    精神神経学雑誌 (公社)日本精神神経学会 (2013特別) S - 681 0033-2658 2013/05
  • 高橋秀俊, 豊永公司, 高橋雄一, 荒井宏, 船曳康子, 宮川真一, 廣常秀人, 本田教一, 齊藤卓弥, 築島健, 吉田佳郎
    総合病院精神医学 (一社)日本総合病院精神医学会 24 (4) 349 - 360 0915-5872 2012/10/15 [Not refereed][Not invited]
     
    日本総合病院精神医学会の学会員を対象に、総合病院における児童青年期精神科診療の実態について調査を行った。平成24年7月学会誌にアンケート用紙を同封した。更に、学会のメーリングリストでアンケート用紙のファイルを添付した。140名から回答を得た。同一施設内複数回答は3施設(各施設2名ずつ)のみと少数であった。約半数が精神科病床を有しており、精神科病床を有する施設は大学病院や精神科病院に多かった。半数が一般病院、1/4が大学病院に勤務しており、合計で8割近くが総合病院に勤務していた。所属施設の精神科医師の人数は、最頻値は、常勤・非常勤を合わせると3名で、常勤に限ると1名となり、少数の精神科医で対応していた。回答者の所属施設の8割で児童青年期精神科外来を実施していた。うち、8割以上の施設が精神科で実施していた。入院診療については、成人と共用の施設で実施、実施していない施設が各4割以上あった。児童青年期精神医療に関する研修は4割が受けたことがなかった。
  • 成重 竜一郎, 川島 義高, 大高 靖史
    臨床精神医学 アークメディア 41 (9) 1255 - 1261 0300-032X 2012/09 [Refereed][Not invited]
  • 川島 義高, 伊藤 敬雄, 成重 竜一郎
    Japanese journal of clinical psychiatry アークメディア 39 (11) 1397 - 1404 0300-032X 2010/11 [Not refereed][Invited]
  • 川島 義高, 伊藤 敬雄, 中井 有希
    Japanese journal of clinical psychiatry アークメディア 38 (9) 1279 - 1286 0300-032X 2009/09 [Refereed][Not invited]
  • RD Strous, KA Nolan, R Lapidus, L Diaz, T Saito, HM Lachman
    AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS 120B (1) 29 - 34 0148-7299 2003/07 [Refereed][Not invited]
     
    We have previously reported that increased aggressive behavior in schizophrenic patients may be associated with a polymorphism at codon 158 of the catechol O-methyltransferase (COMT) gene that encodes a low enzyme activity variant. The finding has been replicated by one group, but not others. The discordant findings could be due to statistical errors or methodological issues in the assessment of aggressive/violent behavior. Consequently, additional studies are needed. Patients with schizophrenia (SZ) were assessed for violent behavior using the Lifetime History of Aggression (LHA) scale, an 11-item. questionnaire that includes Aggression, Self-Directed Aggression, and Consequences/Antisocial Behavior subscales. DNA was genotyped for the COMT 158 polymorphism, as well as a functional polymorphism in the monoamine oxidase A (MAOA) gene promoter. Similar to our previously reported findings, a statistically significant association was found between aggressive behavior in SZ and the COMT 158 polymorphism; mean LHA scores were higher in subjects homozygous for 158Met, the low enzyme activity COMT variant (F(2,105) = 5.616, P = 0.005). Analysis of the major LHA subscales revealed that the association with 158Met was due to high scores on the Aggression, and Self-Directed Aggression subscales, but not the Consequences/Antisocial Behavior subscale. No significant association was detected for the AMOA gene alone. Our findings provide further support that COMT is a modifying gene that plays a role in determining interindividual variability in the proclivity for outward and self-directed aggressive behavior found in some schizophrenic patients. (C) 2003 Wiley-Liss, Inc.
  • KA Nolan, J Volavka, HM Lachman, T Saito
    PSYCHIATRIC GENETICS 10 (3) 109 - 115 0955-8829 2000/09 [Refereed][Not invited]
     
    Serotonergic pathways have been implicated in impulsive and aggressive behavior. Polymorphisms in the regulatory region of the serotonin transporter (5-HTT), in intron 7 of the tryptophan hydroxylase (TPH) gene and in the MAOA gene were previously reported to be associated with mood and anxiety disorders, impulsivity and aggression. In this study, we analyzed these polymorphisms in men and women with schizophrenia or schizoaffective disorder (n = 84) who met our criteria for violence (history of two or more assaults on others) or nonviolence (no history of either assaultive or threatening behavior). In males, a modest association between TPH genotype and history of violence (chi-square test = 6.703, degrees of freedom = 2, P = 0.035) was not statistically significant after correction for multiple comparisons (corrected P = 0.21). The TPH L allele was more frequent in violent males (chi-square = 5.323, degrees of freedom = 1, P = 0.021) but this difference also failed to withstand correction (corrected P = 0.126). No significant associations were found for either the 5-HTT or MAOA polymorphisms in males or females. These results tend to support previous reports by New et nl. (1996; 1998) of an association between the TPH L allele and impulsive aggression in males with personality disorder, but larger studies are needed. Psychiatr Genet 10:109-115 (C) 2000 Lippincott Williams & Wilkins.
  • T Hallikainen, T Saito, HM Lachman, J Volavka, T Pohjalainen, OP Ryynanen, J Kauhanen, E Syvalahti, J Hietala, J Tiihonen
    MOLECULAR PSYCHIATRY 4 (4) 385 - 388 1359-4184 1999/07 [Refereed][Not invited]
     
    A common 44-base pair insertion/deletion polymorphism in the promoter region of the human serotonin transporter (5-HTT) gene has been observed to be associated with affective illness and anxiety-related traits, This biallelic functional polymorphism, designated long (L) and short (S), affects 5-HTT gene expression since the S promoter is less active than the L promoter. Since there is strong evidence of a disturbance in brain serotonergic transmission among antisocial, impulsive, and violent type 2 alcoholic subjects, we decided to test the hypothesis that the frequency of the S allele, which is associated with reduced 5-HTT gene expression, is higher among habitually violent type 2 alcoholics when compared with race and gender-matched healthy controls and non-violent late-onset (type 1) alcoholics, The 5-HTT promoter genotype was determined by a PCR-based method in 114 late onset (type 1) non-violent alcoholics, 51 impulsive violent recidivistic offenders with early onset alcoholism (type 2), and 54 healthy controls, All index subjects and controls were white Caucasian males of Finnish origin. The S allele frequency was higher among type 2 alcoholics compared with type 1 alcoholics chi(2)=4.86, P=0.028 and healthy controls chi(2) = 8.24, P = 0.004, The odds ratio for SS genotype vs LL genotype was 3.90, 95% CI 1.37-11.11, P=0.011 when type 2 alcoholics were compared with healthy controls. The results suggest that the 5-HTT 'S' promoter polymorphism is associated with an increased risk for early onset alcoholism associated with antisocial personality disorder and impulsive, habitually violent behavior.

MISC

Association Memberships

  • 日本総合病院精神医学会   日本精神科診断学会   日本医学英語教育学会   関東子ども精神保健学会   日本サイコセラピー学会   日本医学教育学会   日本ADHD学会   JAPANESE SOCIETY MOOD DISORDERS   日本児童青年期精神医学会   Society for Neuroscience   American Psychological Association   The Royal College of Psychiatrists   World Federation of ADHD   Society of Biological Psychiatry   American Academy of Child and Adolescent Psychiatry   American Psychiatric association   日本精神神経学会   

Research Projects

  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)
    Date (from‐to) : 2022/04 -2026/03 
    Author : 岸 玲子, 宮下 ちひろ, 小林 澄貴, 伊藤 佐智子, 山崎 圭子, アイツバマイ ゆふ, 山口 健史, 田村 菜穂美, 齊藤 卓弥
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
    Date (from‐to) : 2022/04 -2026/03 
    Author : 足立 匡基, 高橋 芳雄, 和久田 学, 廣田 智也, 西村 倫子, 門田 麗, 森 裕幸, 三上 美咲, 齊藤 卓弥
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2021/04 -2026/03 
    Author : 柳生 一自, 齊藤 卓弥, 横澤 宏一, 白石 秀明
     
    私たちは北海道大学にある2台の脳磁計（Magnetoencephalography: MEG）を光ファイバーで接続し、映像・音声での仮想的対面を可能とするDual-MEGシステムを構築した。さらによりリアルな対面を行えるようカメラとプロジェクタの視差をなくすハーフミラーを用い正面からの視線合致を可能とした。このDual-MEGシステムを用いて、実対面（相手の映像と実際に対面している状況）、擬対面（録画された相手の映像と対面している状況）とを用いて、被験者に判断させる課題を行った。結果、本人は擬対面だと答えている（実対面には気付いていない）にも関わらず、右下前頭部におけるθ波の活動が、映像が実対面では脱同期、擬対面では過同期をすることを明らかにした。すなわち意識レベルでは相手の存在に気づいていない（非意識）にも関わらず、「相手の存在」を脳内で表象化する機構が同部位に存在することを示した。さらに考察をすすめこの二条件の違いは、他者との無意識の交互作用にあること、そのやりとりはfacial mimicry（表情模倣）にあることを推論した。こうした点は進化学的見地、発達学的見地からも合理的であると考えられ、トップダウンの認知とは別の、ボトムアップによって他者が象徴化される機構を示しているのかもしれない。こうした中前頭回を中心としたこの非意識下における他者存在の象徴化については統計学的な検討を深めた上で、研究成果については現在論文化を進めている。さらに2021年度は、研究対象として健常者同士によるコミュニケーションモジュールの同定、解析方法としては単一被験者の脳活動におけるモジュール同定を目的とした周波数解析と事象関連同期・脱同期の解析を進めた。熟練した脳磁図計測および解析方法を行える研究協力者が必要であり、育成を進めている。
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
    Date (from‐to) : 2020/04 -2024/03 
    Author : 横澤 宏一, 小野 弓絵, 齊藤 卓弥, 柳生 一自, 豊巻 敦人
     
    コミュニケーションは特に人類において発達した社会的行動の基礎をなす。本研究の第１の目的は、その神経基盤を明らかにすることである。このため、ミリ秒レベルの時間分解能と数ミリメートル程度の空間分解能を併せ持つ脳磁計を２台、光ファイバーで連結したDual MEGを用い、コミュニケーション中の脳活動の同時記録（ハイパースキャニング）を実施してきた。音響・映像機器により２人の実験参加者は仮想的に対面でき、自然なコミュニケーションが可能である。 コミュニケーションには言語コミュニケーションと非言語コミュニケーションがある。実際のコミュニケーションは、これらが複合し絶え間なく入れ替わる極めて複雑なプロセスである。そこで本研究は、非言語コミュニケーションと言語コミュニケーションを個別に実験、解析したのち、統合するというプロセスで推進中である。 これまでは主に非言語コミュニケーションに着目した研究を実施してきた。相手と実時間で対面している場合（実対面映像）と、少し前に録画した映像（録画映像）と対面している場合の脳活動を比較した。その結果、実験参加者は実対面映像と録画対面映像をほとんど区別できないが、実対面している場合に特異な活動が右前頭脳領域に生じることを見出した。つまり、人の意識に上らない脳活動が非言語コミュニケーションを成立させている可能性があることがわかった。一方で、この課題のようにコミュニケーションが明示的ではない場合、コミュニケーションの成立を定義するのが難しいことが明らかになってきた。コミュニケーションが成立した瞬間をとらえないと脳の機能領野間の相関・因果関係を解析することが難しい。以上が初年度の成果と、新たに明らかになった課題である。
  • 日本学術振興会：科学研究費助成事業 基盤研究(A)
    Date (from‐to) : 2019/04 -2023/03 
    Author : 岸 玲子, 池田 敦子, 小林 澄貴, 齊藤 卓弥, 湊屋 街子, 山崎 圭子, 中島 そのみ, 宮下 ちひろ, 白石 秀明, アイツバマイ ゆふ, 三浦 りゅう
     
    本研究は、出生コーホート研究で保存された母体血・臍帯血および学童期から思春期に採取した児の尿を用いて、胎児期および生後の環境化学物質曝露が児のアレルギー、神経行動発達、第二次性徴等のアウトカムへ及ぼす影響についてリスク評価を行うことを目的とした。 令和3年度は、出生コーホートの参加者について11歳で第二次性徴に関する調査票1182件、12歳で小学校の学校健診記録から転記する身長体重調査票1236件、15歳で中学校の身長体重調査票1440件、17歳調査1787件を発送した。回収数は11歳812件（回収率68.7.％）、12歳771件（回収率62.4％）、15歳815件（回収率56.5％）、17歳855件（47.8％）であった。生後のアウトカム評価として、これまでの質問票調査によるアレルギー、神経行動発達、第二次性徴の評価を行った。脳波調査では、有機フッ素化合物（PFAS）の胎児期曝露が児の認知機能に関連する可能性を検討した。妊娠初期母体血清中のフタル酸7代謝物と第二次性徴発来のタイミングおよび、成長や肥満などの体格との解析を実施した。
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2016/04 -2020/03 
    Author : Yagyu Kazuyori
     
    There are various intermediate phenotypes of clinically expressed dyslexia, not only pure dyslexia, but also abnormalities in underlying brain function and comorbid disorders. This study aimed to elucidate the pathophysiology of brain function, intermediate phenotype, and clinical phenotype of dyslexia. In a functional brain study, magnetoencephalography revealed characteristic changes in brain activity in the bilateral inferior frontal and left superior temporal lobes of children with dyslexia. In a clinical phenotypic study, we developed a self-administered questionnaire on reading difficulties applicable to individuals at or above junior high school age. The questionnaire showed sufficient sensitivity and specificity for diagnostic screening of dyslexia. As an intermediate phenotyping study, a questionnaire on specific language disorders and developmental co-motor disorders was developed and they showed clinical usefulness in each study.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)
    Date (from‐to) : 2016/04 -2019/03 
    Author : Kishi Reiko, Kajiwara Junboku, Sata Fumihiro, Saijo Yasuaki, Yoshioka Eiji
     
    To investigate the effects of pre-and postnatal exposure to environmental chemicals on child’s neurodevelopment, puberty onset, and allergies, we evaluated these adverse health impacts in terms of single and multiple exposures, as well as gene-environment interaction. A significant decreasing secular trend of urinary MEHP concentration of 7 years old children was found in the sample collected between 2012 and 2017. Prenatal exposures to MECPP was associated with increase a risk of behavioral problems among 5 years old children and MnBP, MiBP, MEHP were associated with early puberty onset among girls. Prenatal exposure to BPA did not have any associations with neurodevelopment or puberty onset. Prenatal exposure to multiple chemicals disrupted sex hormone levels in cord blood, especially MEHP and PFOS were highly contributions to hormone levels. A significant decreasing 2D:4D ratio was found in cord blood XbaI polymorphism of estrogen receptor 1 gene.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research
    Date (from‐to) : 2016/04 -2018/03 
    Author : Reiko kishi, AIT BAMAI Yu, KOBAYASHI Sumitaka
     
    We targeted DNA methylation as a mediator between prenatal exposure to environmental chemicals and attention-deficit/hyperactivity disorder (ADHD). We assessed methylation levels at 450K cytosine-guanine dinucleotide sites (CpGs) in cord blood DNA using an Illumina HumanMethylation 450 BeadChip, and examined association between methylation and prenatal exposure to perfluoroalkyl substances, phthalates, and bisphenol A. The epigenome-wide analyses (EWAS) showed significant differences in methylation associated with prenatal exposure. To investigate prospective association between DNA methylation at birth and ADHD-related behavior at 6 years, we extracted DNA from cord blood of ADHD groups (n=245) identified with ADHD rating scale (ADHD-RS) and control groups （n=317）. Using a next-generation sequencer, we have quantified methylation levels at CpGs that showed significant association with prenatal exposure in the EWAS.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2015/04 -2018/03 
    Author : Saito Takuya
     
    In this study, subjects were obtained from the principals and guardians for elementary and junior high school students in Sapporo City between the ages of 6 and 18, and how the first year's death / death idea changed in the second year 118 college and senior high school students who responded for 2 consecutive years were evaluated. At the same time, psychology and communication related to suicidal behavior in child adolescence, childhood adolescence, childhood adolescence, and childhood adolescence are carried out by practicing dilution desire idea, depression scale, BCL (child behavior check list), Birleson: self-filled depression evaluation scale (DSRS-C) Ability, and developmental disorder. We analyzed changes in suicidal ideation and factors related to suicidal ideation.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2008 -2010 
    Author : SAITO Takuya, OKUBO Yoshiro, TATENO Amane
     
    Depression is a major mental health problem in child and adolescent and the prevalence is estimated approximately 5-8% and is gradually increased. However, there is no biological maker for child and adolescent for diagnosis and treatment. To find association between biomarkers and symptoms for child depression is important. 8 major depressive disorder child and age matched non-depressive 7clinical samples are participated in an MRI experiment. Whole-brain analyses were conducted and the results of these analyses were examined for potential relationships with depression severity, Quality of life and General psychopathology.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
    Date (from‐to) : 2007 -2010 
    Author : OKUBO Yoshiro, SAITO Takuya, TATENO Amane, ICHIMIYA Tetsuya, KOEDA Michihiko
     
    Using positron emission tomography (PET) and different radioligands, we aimed to elucidate altered dopamine transmission in patients with schizophrenia. Using two different radioligands, [^<11>C]NNC112 and [^<11>C]SCH23390, we measured dopamine D1 receptor binding in patients with chronic schizophrenia and healthy controls. In patients with schizophrenia, the binding potentials of both ligands were significantly lower in the striatum and cortical regions than those of healthy controls. We measured presynaptic dopamine synthesis using PET with L-[β-^<11>C]DOPA and found that patients with schizophrenia showed higher dopamine synthesis in the left caudate nucleus, and that dopaminergic transmission in the thalamus and right temporal cortex might be implicated in the expression of symptoms in schizophrenia. Finally, we performed PET using [^<11>C]PE2I in patients with schizophrenia and healthy subjects to investigate dopamine transporter binding. Dopamine transporter binding in the thalamus of patients with schizophrenia was significantly higher than in control subjects. There were significant correlations between dopamine transporter binding and clinical symptom scores suggesting that altered dopamine transporter binding in the thalamus might be related to the pathophysiology and clinical symptoms of schizophrenia.
  • 日本学術振興会：科学研究費助成事業 挑戦的萌芽研究
    Date (from‐to) : 2007 -2009 
    Author : 高柳 和江, 齊藤 卓弥, 伊藤 要子
     
    心からの感動の笑いを学んだ職員によるケアで患者さんの治癒力が高まるエビデンスをだすことを目的として、病院職員に研修を行った。【対象】参加者は病院内の各部署からの41名(医師6,看護師20,薬剤部2,検査部2,放射線部2,臨床工学部1,PT1,栄養部1,福祉相談部1,事務部5)。【方法】自然の形で笑いを引き出す2日間の研修を4回行った。カリキュラムは,笑いの理論学習,自然な形で笑いを引き出す手法の実践,実習、体感トレーニングで構成された。この笑医セラピスト41名が,新たに院内から募った2チーム(計80名)に対して2日間の研修実習を行った。参加度,理解度を取り,POMS (Profile of mode score),心のパワーアップ(PU)スケール(高柳作成)を用いた。これは,満足度,余裕度、患者に対する意識の変化,自己効力感の変化をみるものである。また、一人の脳卒中後うつ患者にコア笑医セラピストによる笑医療法を行い、この患者の行動変容をFIM評価で検証した。【結果】研修前後で参加度、理解度はそれぞれ有意に改善した。POMSは,緊張・不安,抑うつ・落ち込み、怒り・敵意は大きく低下し,疲労と混乱は減少した。活気は大きく高まった(P<0.05)。心のPUスケールで活力が出る,安全だ,頭の回転が良くなる,効率が良い,幸せだ,などという結果が出た。また、身体的にも不眠が改善,持病の頑固な肩こりが治癒,腰痛の軽減などの声があった。実症例においても,脳卒中後のうつの70歳男性患者に,笑医セラピスト研修生が第62-70病日の間に3回面会し動機づけしたところ,うつ状態が改善し,ADLが自立,17日後にはFIM評価125/126になり退院し、その2カ月後に医師として職場復帰した本研究は、土浦協同病院(院長藤原秀臣)の全面的協力を得ており、土浦協同病院倫理委員会で本研究が認められた。

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