2022/04/11 更新

写真a

タカハシ　ナガヒデ
髙橋　長秀
TAKAHASHI Nagahide
所属
医学部附属病院 親と子どもの心療科 准教授
大学院担当
大学院医学系研究科
職名
准教授

学位 1

  1. 博士（医学） （ 2007年3月   名古屋大学 ） 

学位の先頭へ▲

研究キーワード 6

  1. 遺伝統計学

  2. 自閉スペクトラム症

  3. 統合失調症

  4. 注意欠如多動症

  5. ポリジェニックリスクスコア

  6. うつ病

研究キーワードの先頭へ▲

研究分野 1

  1. ライフサイエンス / 精神神経科学

研究分野の先頭へ▲

経歴 4

  1. 名古屋大学   大学院医学系研究科親と子どもの心療学   准教授

    2021年10月 - 現在

  2. 名古屋大学医学部附属病院   親と子どもの心療科   講師

    2020年4月 - 2021年9月

  3. 浜松医科大学   子どものこころの発達研究センター   特任准教授

    2019年4月 - 2020年3月

  4. 米国マウントサイナイ医科大学分子精神医学研究室   分子精神医学教室   ポスドク研究員

    2007年4月 - 2010年3月

経歴の先頭へ▲

学歴 1

  1. 名古屋大学   医学部

    - 2000年

    　 詳細を見る

    国名： 日本国

学歴の先頭へ▲

受賞 1

  1. 先進医薬研究振興財団 海外留学助成

    2008年  

    　詳細を見る

    受賞国：日本国

受賞の先頭へ▲
 

論文 59

  1. Long-term effect of persistent postpartum depression on children's psychological problems in childhood. 査読有り

    Tainaka H, Takahashi N, Nishimura T, Okumura A, Harada T, Iwabuchi T, Rahman MS, Nomura Y, Tsuchiya KJ

    Journal of affective disorders   305 巻   頁： 71 - 76   2022年5月

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    担当区分：責任著者   記述言語：英語   出版者・発行元：Journal of Affective Disorders  

    Background: Maternal postpartum depression (PPD) is a well-established risk factor for psychological problems in children; however, little is known about the sustained impact of persistent PPD patterns and severity on these problems in children. Methods: Data were obtained from mothers (N = 714) and children (N = 768) from the Hamamatsu Birth Cohort for Mothers and Children. Maternal depression was measured using the Edinburgh Postpartum Depression Scale at 2, 4, 10 weeks and 10 months postpartum. Children's internalizing and externalizing problems were assessed using the Strengths and Difficulties Questionnaire at 6 years and 8–9 years old. Mothers were divided into 4 groups based on the trajectory of their PPD persistence: “No PPD,” “Transient PPD,” “Worsening PPD” and “Persistent PPD.” Linear regression analysis was used to examine the association of PPD persistence and severity with children's internalizing and externalizing problems. Results: “Persistent PPD” was significantly associated with children's internalizing problems at 6 years old (Coefficient [95%CI] = 2.74 [1.30–4.19], P < .001), but no association was found at 8–9 years old. No associations were found between PPD severity and children's internalizing and externalizing problems in either age category. Limitations: “Persistent PPD” and “Worsening PPD” groups had a relatively small sample size. The mothers' depression statuses were not ascertained simultaneously with the children's behavioral assessments. There was no information regarding the mothers' treatment for PPD. Conclusion: PPD persistence negatively affected children's internalizing problems but was not long-lasting. Future studies are needed to identify protective factors against PPD persistence in children's psychological problems.

    DOI： 10.1016/j.jad.2022.02.061

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  2. Perfluorooctanoate and perfluorooctane sulfonate in umbilical cord blood and child cognitive development: Hamamatsu Birth Cohort for Mothers and Children (HBC Study).

    Oh J, Shin HM, Nishimura T, Rahman MS, Takahashi N, Tsuchiya KJ

    Environment international   163 巻   頁： 107215   2022年3月

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    記述言語：英語  

    DOI： 10.1016/j.envint.2022.107215

    PubMed

  3. Identification of neurodevelopmental transition patterns from infancy to early childhood and risk factors predicting descending transition.

    Kato T, Nishimura T, Takahashi N, Harada T, Okumura A, Iwabuchi T, Nomura Y, Senju A, Tsuchiya KJ, Takei N

    Scientific reports   12 巻 ( 1 ) 頁： 4822   2022年3月

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    記述言語：英語   出版者・発行元：Scientific reports  

    It is unclear whether neurodevelopmental progress from infancy to early childhood remains stable. Moreover, little is known about the risk factors, if any, affecting neurodevelopmental descending transition patterns and the relationship between these patterns and later childhood adaptive behaviours. We used data of 875 children from the Hamamatsu Birth Cohort Study in Japan. Children's neurodevelopment at 18 and 32 months and adaptive behaviours at 40 months were evaluated. Perinatal factors and infant overweight status at 18 months were investigated to identify descending-transition-associated risk factors. In the latent transition analysis, ultimately, three classes were identified for each time-point, resulting in nine transition patterns; among them, 10.4% of children showed descending class shifts (normal to delayed class). Such decelerated growth was predicted by maternal pre-pregnancy overweight status (odds ratio [OR] 2.49; 95% confidence interval [CI] 1.23, 5.02), low maternal educational history (OR 1.20; 95% CI 1.04, 1.36), and infant overweight status at 18 months (OR 5.89; 95% CI 1.26, 27.45). Children with descending transition showed poor functioning in adaptive behaviours at the age of 40 months. To prevent subsequent poor adaptive functioning, it may be necessary to consider that a certain percentage of children show decelerated growth.

    DOI： 10.1038/s41598-022-08827-4

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  4. Perceived Social Support Partially Mediates the Impact of Temperament and Character on Postpartum Depression

    Nakamura Yukako, Takahashi Nagahide, Yamauchi Aya, Morikawa Mako, Okada Takashi, Ozaki Norio

    FRONTIERS IN PSYCHIATRY   12 巻   頁： 816342   2022年1月

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    担当区分：筆頭著者,　責任著者   記述言語：日本語   出版者・発行元：Frontiers in Psychiatry  

    Introduction: Temperament and character of pregnant women, especially harm avoidance (HA) and self-directedness (SD) have been identified as risk factors for postpartum depression, in addition to poor social support. However, the relationship between these personality traits and social support for depressive symptoms after delivery has not been examined. Methods: Data were extracted from a prospective cohort survey on pregnant women conducted in Nagoya, Japan that included the Temperament and Character Inventory (TCI), the Social Support Questionnaire (J-SSQ), and the Edinburgh Postnatal Depression Scale (EPDS) at approximately week 25 and 1 month postpartum. A mediation analysis using structural equation modeling (SEM) was used to test if social support in pregnancy is a mediator between personality traits and postpartum depressive symptoms. Results: Thousand five hundred and fifty-nine women were included in the analysis. Both harm avoidance and SD were significantly associated with depressive symptoms (total effect: β [SE], 0.298 [0.041], P < 0.001 for harm avoidance; total effect: β [SE], −0.265 [0.067], P < 0.001 for SD). Mediation analysis showed that the effect of harm avoidance on depressive symptoms was partially mediated by low social support (direct effect: β [SE], 0.193 [0.004], P < 0.001; indirect effect: β [SE], 0.082 [0.034], P = 0.015). Self-directedness on depressive symptoms was not found to be mediated by low social support. Conclusion: Results indicate that poor social support worsens depressive symptoms in women with high HA during pregnancy. Limitations include a possible selection bias due to the limited target facilities; most variables being evaluated based on self-report questionnaires, and different number of samples available for analysis between harm avoidance and SD.

    DOI： 10.3389/fpsyt.2021.816342

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  5. Early temperament as a predictor of language skills at 40 months.

    Ishikawa-Omori Y, Nishimura T, Nakagawa A, Okumura A, Harada T, Nakayasu C, Iwabuchi T, Amma Y, Suzuki H, Rahman MS, Nakahara R, Takahashi N, Nomura Y, Tsuchiya KJ

    BMC pediatrics   22 巻 ( 1 ) 頁： 56   2022年1月

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    記述言語：英語   出版者・発行元：BMC Pediatrics  

    Background: Mastering language involves the development of expressive and receptive skills among children. While it has been speculated that early temperament plays a role in the acquisition of language, the actual mechanism has not yet been explored. We investigated whether temperament at 18 months predicted expressive or receptive language skills at 40 months. Methods: A representative sample of 901 children and their mothers who were enrolled and followed-up longitudinally in the Hamamatsu Birth Cohort for Mothers and Children study was included in the analysis. Child temperament was measured at 18 months using the Japanese version of the Early Childhood Behavior Questionnaire. Expressive and receptive language skills were measured at 40 months using the Mullen Scales of Early Learning. Results: The multiple regression analysis, adjusting for potential confounders, suggested that higher motor activation (fidgeting) at 18 months was associated with lower expressive and receptive language skills at 40 months. Higher perceptual sensitivity was associated with higher expressive and receptive language skills at 40 months. Conclusions: Specific temperament at 18 months of age predicted the development of the child’s expressive and receptive language skills at 40 months.

    DOI： 10.1186/s12887-022-03116-5

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  6. Exploration of Sleep Parameters, Daytime Hyperactivity/Inattention, and Attention-Deficit/Hyperactivity Disorder Polygenic Risk Scores of Children in a Birth Cohort in Japan

    Takahashi Nagahide, Okumura Akemi, Nishimura Tomoko, Harada Taeko, Iwabuchi Toshiki, Rahman Md Shafiur, Tsuchiya Kenji J.

    JAMA NETWORK OPEN   5 巻 ( 1 ) 頁： e2141768   2022年1月

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    記述言語：日本語   出版者・発行元：JAMA Network Open  

    DOI： 10.1001/jamanetworkopen.2021.41768

    Web of Science

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  7. Autism spectrum disorder comorbid with obsessive compulsive disorder and eating disorder in a woman with NBEA deletion

    Kato Hidekazu, Kushima Itaru, Yoshimi Akira, Ishizuka Kanako, Kimura Hiroki, Aleksic Branko, Takahashi Nagahide, Okada Takashi, Ozaki Norio

    PSYCHIATRY AND CLINICAL NEUROSCIENCES   76 巻 ( 1 ) 頁： 36 - 38   2022年1月

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    記述言語：日本語   出版者・発行元：Psychiatry and Clinical Neurosciences  

    DOI： 10.1111/pcn.13309

    Web of Science

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  8. Efficacy and safety of fixed doses of intranasal Esketamine as an add-on therapy to Oral antidepressants in Japanese patients with treatment-resistant depression: a phase 2b randomized clinical study

    Takahashi Nagahide, Yamada Aya, Shiraishi Ayako, Shimizu Hiroko, Goto Ryosuke, Tominaga Yushin

    BMC PSYCHIATRY   21 巻 ( 1 ) 頁： 526   2021年10月

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    記述言語：日本語   出版者・発行元：BMC Psychiatry  

    Background: Esketamine nasal spray (Spravato) in conjunction with oral antidepressants (ADs) is approved in the European Union, United States, and other markets for treatment-resistant depression (TRD). Efficacy, safety, and tolerability of esketamine nasal spray in Japanese patients with TRD needs to be assessed. Methods: This Phase 2b, randomized, double-blind (DB), placebo-controlled study was conducted in adult Japanese patients with TRD meeting the Diagnostic and Statistical Manual of Mental Disorders (fifth edition) criteria of major depressive disorder with nonresponse to ≥ 1 but < 5 different ADs in the current episode at screening. Patients were treated with a new oral AD for 6 weeks (prospective lead-in phase); nonresponders were randomized (2:1:1:1) to placebo or esketamine (28-, 56-, or 84-mg) nasal spray along with the continued use of AD for 4 weeks (DB induction phase). Responders (≥50% reduction from baseline in the Montgomery-Asberg Depression Rating Scale [MADRS] total score) from the DB induction phase continued into the 24-week posttreatment phase and patients who relapsed could participate in a 4-week open-label (OL) second induction (flexibly-dosed esketamine). The primary efficacy endpoint, change from baseline in the MADRS total score at Day 28 in the DB induction phase, was based on mixed-effects model using repeated measures pairwise comparisons using a Dunnett adjustment. Results: Of the 202 patients randomized in the DB induction phase (esketamine [n = 122] or placebo [n = 80]), the MADRS total scores decreased from baseline to Day 28 of the DB induction phase (− 15.2, − 14.5, − 15.1, and − 15.3 for esketamine 28 mg, 56 mg, 84 mg, and placebo groups, respectively), indicating an improvement in depressive symptoms; however, the difference between the esketamine and placebo groups was not statistically significant. The most common treatment-emergent adverse events during the DB induction phase in the combined esketamine group (incidences ranging from 12.3 to 41.0%) were blood pressure increased, dissociation, dizziness, somnolence, nausea, hypoaesthesia, vertigo, and headache; the incidence of each of these events was > 2-fold higher than the corresponding incidence in the placebo group. Conclusions: Efficacy of esketamine plus oral AD in Japanese TRD patients was not established; further investigation is warranted. All esketamine doses were safe and tolerated. Trial registration: ClinicalTrials.gov Identifier: NCT02918318. Registered: 28 September 2016.

    DOI： 10.1186/s12888-021-03538-y

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  9. 特集 精神医療に関する疫学のトピック-記述疫学,リスク研究からコホート研究まで 子どもの神経発達と神経発達症を知るための疫学研究プロジェクト-浜松母と子の出生コホート研究(HBC Study)について

    土屋 賢治, 西村 倫子, 奥村 明美, 原田 妙子, 岩渕 俊樹, 高橋 長秀

    精神医学   63 巻 ( 4 ) 頁： 469 - 477   2021年4月

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    出版者・発行元：株式会社医学書院  

    DOI： 10.11477/mf.1405206315

    CiNii Research

  10. Associations Among Maternal Metabolic Conditions, Cord Serum Leptin Levels, and Autistic Symptoms in Children.

    Iwabuchi T, Takahashi N, Nishimura T, Rahman MS, Harada T, Okumura A, Kuwabara H, Takagai S, Nomura Y, Matsuzaki H, Ozaki N, Tsuchiya KJ

    Frontiers in psychiatry   12 巻   頁： 816196   2021年

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    記述言語：英語   出版者・発行元：Frontiers in Psychiatry  

    Introduction: Accumulating evidence has shown that maternal metabolic conditions, such as pre-pregnancy overweight, diabetes mellitus, and hypertensive disorders of pregnancy (HDP) are potential risk factors of autism spectrum disorder (ASD). However, it remains unclear how these maternal conditions lead to neurodevelopmental outcomes in the offspring, including autistic symptoms. Leptin, an adipokine that has pro-inflammatory effects and affects fetal neurodevelopment, is a candidate mediator of the association between maternal metabolic factors and an increased risk of ASD. However, whether prenatal exposure to leptin mediates the association between maternal metabolic conditions and autistic symptoms in children has not been investigated yet. Methods: This study investigated the associations between mothers' metabolic conditions (pre-pregnancy overweight, diabetes mellitus during or before pregnancy, and HDP), leptin concentrations in umbilical cord serum, and autistic symptoms among 762 children from an ongoing cohort study, using generalized structural equation modeling. We used the Social Responsive Scale, Second Edition (SRS-2) at 8–9 years old to calculate total T-scores. Additionally, we used the T-scores for two subdomains: Social Communication and Interaction (SCI) and Restricted Interests and Repetitive Behavior (RRB). Results: Umbilical cord leptin levels were associated with pre-pregnancy overweight [coefficient = 1.297, 95% confidence interval (CI) 1.081–1.556, p = 0.005] and diabetes mellitus (coefficient = 1.574, 95% CI 1.206–2.055, p = 0.001). Furthermore, leptin levels were significantly associated with SRS-2 total T-scores (coefficient = 1.002, 95% CI 1.000–1.004, p = 0.023), SCI scores (coefficient = 1.002, 95% CI 1.000–1.004, p = 0.020), and RRB scores (coefficient = 1.001, 95% CI 1.000–1.003, p = 0.044) in children. Associations between maternal metabolic factors and autistic symptoms were not significant. Discussion: The present study uncovered an association between cord leptin levels and autistic symptoms in children, while maternal metabolic conditions did not have an evident direct influence on the outcome. These results imply that prenatal pro-inflammatory environments affected by maternal metabolic conditions may contribute to the development of autistic symptoms in children. The findings warrant further investigation into the role of leptin in the development of autistic symptoms.

    DOI： 10.3389/fpsyt.2021.816196

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  11. 発達障がいの環境的危険因子～現在の知見から今後の研究に向けて

    土屋 賢治, 西村 倫子, 奥村 明美, 原田 妙子, 岩渕 俊樹, Mohammad Shafiur RAHMAN, 高橋 長秀

    日本毒性学会学術年会   48.1 巻 ( 0 ) 頁： S16-4   2021年

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    記述言語：日本語   出版者・発行元：日本毒性学会  

    <p>発達障がい（神経発達症）として整理される2つの精神神経疾患，自閉スペクトラム症（ASD）と注意欠如・多動症（ADHD）は，乳幼児期に顕在化し，多様な予後を示す。その有病率は，ASDが1～3％，ADHDが5～10％と報告されており，社会的な関心を広く集めている。ASD，ADHDの発症には，遺伝的危険因子（genetic risk factor）のみならず，既知の遺伝的変動（genetic variation）と関連のない危険因子，いわゆる「環境的危険因子」（environmental risk factor）の寄与があることが知られている。胎生期の栄養素の不足，重金属やアルコールへの曝露，胎生期～乳児期における大気中のディーゼル排気粒子，残留有機汚染物質，殺虫剤や農薬への曝露が，ASDやADHDの発症リスクを高めるとの報告がある。また，乳児期のデジタル機器への曝露がASD症状の形成に寄与するのではないかとの報告もなされたところである。演者は，児童精神科を臨床のフィールド，疫学を研究フィールドとする立場から，これらの知見の解釈のあり方について検討を加える。また，知見の不足に対して，研究者がどのようにアプローチすべきかについて，考察する。</p>

    DOI： 10.14869/toxpt.48.1.0_s16-4

    CiNii Research

  12. 特集 日本の周産期事情update-出生コホート研究からわかったこと-Ⅱ 各論 12.周産期の環境と乳幼児の神経発達

    田井中 華恵, 高橋 長秀, 土屋 賢治

    産婦人科の実際   69 巻 ( 2 ) 頁： 125 - 130   2020年2月

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    出版者・発行元：金原出版  

    DOI： 10.18888/sp.0000001176

    CiNii Research

  13. [Relationship of psychopathological symptoms and cognitive function to subjective quality of life in patients with chronic schizophrenia].

    Tomita K, Takahashi N, Saito S, Maeno N, Iwamoto K, Yoshida K, Kimura H, Iidaka T, Ozaki N

    Seishin shinkeigaku zasshi = Psychiatria et neurologia Japonica   113 巻 ( 2 ) 頁： 135 - 43   2011年

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    記述言語：日本語  

    PubMed

  14. An association study of tachykinin receptor 3 gene with schizophrenia in the Japanese population.

    Saito S, Takahashi N, Maeno N, Ito Y, Aleksic B, Usui H, Iidaka T, Inada T, Ozaki N

    Neuroreport   19 巻 ( 4 ) 頁： 471 - 3   2008年3月

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    記述言語：英語  

    DOI： 10.1097/WNR.0b013e3282f600b4

    PubMed

  15. An association between serotonin receptor 3B gene (HTR3B) and treatment-resistant schizophrenia (TRS) in a Japanese population.

    Ji X, Takahashi N, Branko A, Ishihara R, Nagai T, Mouri A, Saito S, Maeno N, Inada T, Ozaki N

    Nagoya journal of medical science   70 巻 ( 1-2 ) 頁： 11 - 7   2008年3月

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    記述言語：英語  

    PubMed

  16. Association study between the transferrin gene and schizophrenia in the Japanese population

    Maeno Nobuhisa, Takahashi Nagahide, Saito Shinichi, Ji Xiaofei, Branko Aleksic, Ishihara Ryoko, Yoshida Keizo, Inada Toshiya, Iidaka Tetsuya, Ozaki Norio

    NEUROREPORT   18 巻 ( 5 ) 頁： 517 - 520   2007年3月

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    記述言語：日本語  

    Web of Science

  17. Association study between vesicle-associated membrane protein 2 gene polymorphisms and fluvoxamine response in Japanese major depressive patients.

    Saito S, Takahashi N, Ishihara R, Ikeda M, Suzuki T, Kitajima T, Yamanouchi Y, Iwata N, Yamada M, Yoshida K, Inada T, Ozaki N

    Neuropsychobiology   54 巻 ( 4 ) 頁： 226 - 30   2006年

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    記述言語：英語  

    DOI： 10.1159/000100777

    PubMed

  18. Elevated risk of attention deficit hyperactivity disorder (ADHD) in Japanese children with higher genetic susceptibility to ADHD with a birth weight under 2000 g.

    Rahman MS, Takahashi N, Iwabuchi T, Nishimura T, Harada T, Okumura A, Takei N, Nomura Y, Tsuchiya KJ

    BMC medicine   19 巻 ( 1 ) 頁： 229   2021年9月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BMC Medicine  

    Background: Both genetic and pre- and perinatal factors, including birth weight, have been implicated in the onset of attention deficit hyperactivity disorder (ADHD) traits among children. This study aimed to elucidate to what extent the genetic risk of ADHD moderates the association between birth weight and ADHD traits among Japanese children. Methods: We conducted a longitudinal birth cohort study (Hamamatsu Birth Cohort for Mother and Children Study) to investigate the association of genetic risk for ADHD and low birth weight with ADHD traits among Japanese children. Out of 1258 children, we included 796 who completed follow-ups at 8 to 9 years of age. Birth weight was categorized as <2000 g, 2000–2499 g, and ≥2500 g. Polygenic risk score for ADHD was generated using the summary data of a large-scale genome-wide association study. The Rating Scale IV (ADHD-RS) assessed ADHD traits (inattention and hyperactivity/impulsivity) based on parental reports. Following previous studies, sex, birth order of the child, gestational age at birth, mother’s age at delivery, educational attainment, pre-pregnancy body mass index, pre-pregnancy or during pregnancy smoking status, alcohol consumption during pregnancy, father’s age, education, and annual family income were considered as covariates. Multivariable negative binomial regression was applied to evaluate the association between birth weight and ADHD traits, while adjusting for potential covariates. The interaction term between birth weight categories and binary polygenic risk was added to the model. Results: Birth weight of 2000–2499 g was not associated with ADHD traits. Birth weight under 2000 g was significantly associated with both inattention and hyperactivity. When accounting for higher and lower genetic risk for ADHD, only those with higher genetic risk and birth weight < 2000 g were associated with inattention (rate ratio [RR] 1.56, 95% CI 1.07–2.27) and hyperactivity (RR 1.87, 95% CI 1.14–3.06). Conclusions: Birth weight under 2000 g, together with the genetic risk of ADHD, contributes to higher levels of ADHD traits among Japanese children aged 8 to 9 years. The suggested association between low birth weight and ADHD is confined to children with a genetic susceptibility to ADHD, indicating the relevance of genetic-environmental interactions in the etiology.

    DOI： 10.1186/s12916-021-02093-3

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    その他リンク： https://link.springer.com/article/10.1186/s12916-021-02093-3/fulltext.html

  19. Peripheral biomarkers of attention-deficit hyperactivity disorder: Current status and future perspective 国際誌

    Takahashi Nagahide, Ishizuka Kanako, Inada Toshiya

    JOURNAL OF PSYCHIATRIC RESEARCH   137 巻   頁： 465 - 470   2021年5月

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    記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Psychiatric Research  

    Attention-deficit hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders, characterized by a persistent pattern of inattention, hyperactivity, and impulsivity. Since the diagnosis of ADHD is defined by operational diagnostic criteria consisting of several clinical symptoms, a number of heterogeneous mechanisms have been considered to be implicated in its pathophysiology. Although no clinically reliable biomarkers are available for the diagnosis of ADHD, several plausible candidate biomarkers have been proposed based on recent advances in biochemistry and molecular biology. This review article summarizes potential peripheral biomarkers associated with ADHD, mainly from recently published case-control studies. These include 1) biochemical markers: neurotransmitters and their receptors, neurotrophic factors, serum electrolytes, and inflammation markers; 2) genetic and epigenetic markers: microRNA, mRNA expression, and peripheral DNA methylation; 3) physiological markers: eye movement and electroencephalography. It also discusses the limitations and future directions of these potential biomarkers for application in clinical practice.

    DOI： 10.1016/j.jpsychires.2021.03.012

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  20. Association Between Genetic Risks for Obesity and Working Memory in Children.

    Takahashi N, Nishimura T, Harada T, Okumura A, Iwabuchi T, Rahman MS, Kuwabara H, Takagai S, Nomura Y, Takei N, Tsuchiya KJ

    Frontiers in neuroscience   15 巻   頁： 749230   2021年

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    記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Frontiers in Neuroscience  

    Introduction: Obesity is highly heritable, and recent evidence demonstrates that obesity is associated with cognitive deficits, specifically working memory. However, the relationship between genetic risks for obesity and working memory is not clear. In addition, whether the effect of these genetic risks on working memory in children is mediated by increased body mass index (BMI) has not been elucidated. Methods: In order to test whether the polygenic risk score (PRS) for obesity in adulthood (adulthood-BMI-PRS) is associated with working memory at 8 years of age, and whether the effect is mediated by childhood BMI, in children from the general population, participants in the Hamamatsu Birth Cohort for Mothers and Children (HBC) study in Hamamatsu, Japan, underwent testing for association of adulthood-BMI-PRS with working memory. HBC data collection began in December 2007 and is ongoing. Adulthood-BMI-PRS values were generated using summary data from the recent genome-wide association study (GWAS) undertaken in Japan, and the significance of thresholds was calculated for each outcome. Outcomes measured included the working memory index (WMI) of Weschler Intelligence Scale-4 (WISC-IV) scores and the BMI at 8 years of age. Gene-set enrichment analysis was conducted to clarify the molecular basis common to adulthood-BMI and childhood-WMI. Mediation analysis was performed to assess whether childhood-BMI of children mediated the association between adulthood-BMI-PRS and working memory. Results: A total of 734 participants (377 males, 357 females) were analyzed. Adulthood-BMI-PRS was associated with lower childhood-WMI (β[SE], −1.807 [0.668]; p = 0.010, corrected) of WISC-IV. Gene-set enrichment analyses found that regulation of neurotrophin Trk receptor signaling (β[SE], −2.020 [6.39]; p = 0.002, corrected), negative regulation of GTPase activity (β[SE], 2.001 [0.630]; p = 0.002, corrected), and regulation of gene expression epigenetic (β[SE], −2.119 [0.664]; p = 0.002, corrected) were enriched in BMI in adulthood and WMI in childhood. Mediation analysis showed that there is no mediation effect of childhood-BMI between the adulthood-BMI-PRS and working memory deficits in children. Conclusion: Adulthood-BMI-PRS was associated with working memory among children in the general population. These genetic risks were not mediated by the childhood-BMI itself and were directly associated with working memory deficits.

    DOI： 10.3389/fnins.2021.749230

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  21. Polygenic risk score analysis revealed shared genetic background in attention deficit hyperactivity disorder and narcolepsy. 査読有り 国際誌

    Takahashi N, Nishimura T, Harada T, Okumura A, Choi D, Iwabuchi T, Kuwabara H, Takagai S, Nomura Y, Newcorn JH, Takei N, Tsuchiya KJ

    Translational psychiatry   10 巻 ( 1 ) 頁： 284 - 284   2020年8月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Translational Psychiatry  

    Attention deficit hyperactive disorder (ADHD) is a highly heritable neurodevelopmental disorder, and excessive daytime sleepiness is frequently observed in ADHD patients. Excessive daytime sleepiness is also a core symptom of narcolepsy and essential hypersomnia (EHS), which are also heritable conditions. Psychostimulants are effective for the symptomatic control of ADHD (primary recommended intervention) and the two sleep disorders (frequent off-label use). However, the common biological mechanism for these disorders has not been well understood. Using a previously collected genome-wide association study of narcolepsy and EHS, we calculated polygenic risk scores (PRS) for each individual. We investigated a possible genetic association between ADHD and narcolepsy traits in the Hamamatsu Birth Cohort for mothers and children (HBC study) (n = 876). Gene-set enrichment analyses were used to identify common pathways underlying these disorders. Narcolepsy PRS were significantly associated with ADHD traits both in the hyperactivity domain (e.g., P-value threshold < 0.05, β [SE], 5.815 [1.774]; P = 0.002) and inattention domain (e.g., P-value threshold < 0.05, β [SE], 5.734 [1.761]; P = 0.004). However, EHS PRS was not significantly associated with either domain of ADHD traits. Gene-set enrichment analyses revealed that pathways related to dopaminergic signaling, immune systems, iron metabolism, and glial cell function involved in both ADHD and narcolepsy. Findings indicate that ADHD and narcolepsy are genetically related, and there are possible common underlying biological mechanisms for this relationship. Future studies replicating these findings would be warranted to elucidate the genetic vulnerability for daytime sleepiness in individuals with ADHD.

    DOI： 10.1038/s41398-020-00971-7

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  22. Association of Genetic Risks With Autism Spectrum Disorder and Early Neurodevelopmental Delays Among Children Without Intellectual Disability. 査読有り 国際誌

    Takahashi N, Harada T, Nishimura T, Okumura A, Choi D, Iwabuchi T, Kuwabara H, Takagai S, Nomura Y, Takei N, Tsuchiya KJ

    JAMA network open   3 巻 ( 2 ) 頁： e1921644   2020年2月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAMA Network Open  

    Importance: Autism spectrum disorder (ASD) is highly heritable, and modest contributions of common genetic variants to ASD have been reported. However, the association of genetic risks derived from common risk variants with ASD traits in children from the general population is not clear, and the association of these genetic risks with neurodevelopment in infants has not been well understood. Objective: To test whether a polygenic risk score (PRS) for ASD is associated with neurodevelopmental progress at age 18 months and ASD traits at age 6 years among children from the general population. Design, Setting, and Participants: In this cohort study, 876 children in the Hamamatsu Birth Cohort for Mothers and Children in Hamamatsu, Japan, underwent testing for the association of an ASD PRS with neurodevelopmental progress and ASD traits. Data collection began in December 2007 and is ongoing. Data analysis was conducted from April to December 2019. Main Outcomes and Measures: Summary data from the largest genome-wide association study were used to generate ASD PRSs, and significance of thresholds was calculated for each outcome. The Autism Diagnostic Observation Schedule 2 was used to measure ASD traits at age 6 years, and the Mullen Scales of Early Learning was used to measure neurodevelopmental progress at age 18 months. Results: Of 876 participants (mean [SD] gestational age at birth, 38.9 [1.6] weeks; 438 [50.0%] boys; 868 [99.1%] Japanese), 734 were analyzed. The ASD PRS was associated with ASD traits (R2 = 0.024; β, 0.71; SE, 0.24; P =.03). The association of ASD PRS with infant neurodevelopment was most pronounced in gross motor (R2 = 0.015; β, -1.25; SE, 0.39; P =.01) and receptive language (R2 = 0.014; β, -1.19; SE, 0.39; P =.02) scores on the Mullen Scales of Early Learning. Gene set enrichment analyses found that several pathways, such as cell maturation (R2 = 0.057; β, -5.28; SE, 1.40; P <.001) and adenylyl cyclase activity and cyclic adenosine monophosphate concentration (R2 = 0.064; β, -5.30; SE 1.30; P <.001), were associated with ASD traits. Gene sets associated with inflammation were commonly enriched with ASD traits and gross motor skills (eg, chemokine motif ligand 2 production: R2 = 0.051; β, -6.04; SE, 1.75; P =.001; regulation of monocyte differentiation: R2 = 0.052; β, -6.63; SE, 1.90; P =.001; and B-cell differentiation: R2 = 0.051; β, 7.37; SE, 2.15; P =.001); glutamatergic signaling-associated gene sets were commonly enriched with ASD traits and receptive language skills (eg, regulation of glutamate secretion: R2 = 0.052; β, -5.82; SE, 1.68; P =.001; ionotropic glutamate receptor signaling pathway: R2 = 0.047; β, 3.54; SE, 1.09; P =.001; and negative regulation of glutamate secretion: R2 = 0.045; β, -5.38; SE, 1.74; P =.002). Conclusions and Relevance: In this study, the ASD PRS was associated with ASD traits among children from the general population. Genetic risks for ASD might be associated with delays in some neurodevelopmental domains, such as gross motor and receptive language skills..

    DOI： 10.1001/jamanetworkopen.2019.21644

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  23. Introduction of the human AVPR1A gene substantially alters brain receptor expression patterns and enhances aspects of social behavior in transgenic mice. 査読有り

    Charles R, Sakurai T, Takahashi N, Elder GA, Gama Sosa MA, Young LJ, Buxbaum JD

    Disease models & mechanisms   7 巻 ( 8 ) 頁： 1013 - 22   2014年8月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1242/dmm.017053

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  24. A randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of osmotic-controlled release oral delivery system methylphenidate HCl in adults with attention-deficit/hyperactivity disorder in Japan. 査読有り 国際誌

    Takahashi N, Koh T, Tominaga Y, Saito Y, Kashimoto Y, Matsumura T

    The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry   15 巻 ( 6 ) 頁： 488 - 98   2014年8月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.3109/15622975.2013.868925

    PubMed

  25. Roles of glial cells in schizophrenia: Possible targets for therapeutic approaches 国際誌

    Takahashi Nagahide, Sakurai Takeshi

    NEUROBIOLOGY OF DISEASE   53 巻   頁： 49 - 60   2013年5月

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  26. Randomized, placebo-controlled, double-blind study assessing the efficacy and safety of paliperidone palmitate in Asian patients with schizophrenia. 査読有り 国際誌

    Takahashi N, Takahashi M, Saito T, Iizumi M, Saito Y, Shimizu H, Matsumura T

    Neuropsychiatric disease and treatment   9 巻   頁： 1889 - 98   2013年

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.2147/NDT.S54051

    PubMed

  27. Copy number variations in alternative splicing gene networks impact lifespan. 査読有り 国際誌

    Glessner JT, Smith AV, Panossian S, Kim CE, Takahashi N, Thomas KA, Wang F, Seidler K, Harris TB, Launer LJ, Keating B, Connolly J, Sleiman PM, Buxbaum JD, Grant SF, Gudnason V, Hakonarson H

    PloS one   8 巻 ( 1 ) 頁： e53846   2013年

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1371/journal.pone.0053846

    PubMed

  28. HDAC2 regulates atypical antipsychotic responses through the modulation of mGlu2 promoter activity. 査読有り 国際誌

    Kurita M, Holloway T, García-Bea A, Kozlenkov A, Friedman AK, Moreno JL, Heshmati M, Golden SA, Kennedy PJ, Takahashi N, Dietz DM, Mocci G, Gabilondo AM, Hanks J, Umali A, Callado LF, Gallitano AL, Neve RL, Shen L, Buxbaum JD, Han MH, Nestler EJ, Meana JJ, Russo SJ, González-Maeso J

    Nature neuroscience   15 巻 ( 9 ) 頁： 1245 - 54   2012年9月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1038/nn.3181

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  29. Haploinsufficiency of Cyfip1 produces fragile X-like phenotypes in mice. 査読有り 国際誌

    Bozdagi O, Sakurai T, Dorr N, Pilorge M, Takahashi N, Buxbaum JD

    PloS one   7 巻 ( 8 ) 頁： e42422   2012年

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1371/journal.pone.0042422

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  30. Genome-wide copy number variation study associates metabotropic glutamate receptor gene networks with attention deficit hyperactivity disorder. 査読有り

    Elia J, Glessner JT, Wang K, Takahashi N, Shtir CJ, Hadley D, Sleiman PM, Zhang H, Kim CE, Robison R, Lyon GJ, Flory JH, Bradfield JP, Imielinski M, Hou C, Frackelton EC, Chiavacci RM, Sakurai T, Rabin C, Middleton FA, Thomas KA, Garris M, Mentch F, Freitag CM, Steinhausen HC, Todorov AA, Reif A, Rothenberger A, Franke B, Mick EO, Roeyers H, Buitelaar J, Lesch KP, Banaschewski T, Ebstein RP, Mulas F, Oades RD, Sergeant J, Sonuga-Barke E, Renner TJ, Romanos M, Romanos J, Warnke A, Walitza S, Meyer J, Pálmason H, Seitz C, Loo SK, Smalley SL, Biederman J, Kent L, Asherson P, Anney RJ, Gaynor JW, Shaw P, Devoto M, White PS, Grant SF, Buxbaum JD, Rapoport JL, Williams NM, Nelson SF, Faraone SV, Hakonarson H

    Nature genetics   44 巻 ( 1 ) 頁： 78 - 84   2011年12月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1038/ng.1013

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  31. Loss of function studies in mice and genetic association link receptor protein tyrosine phosphatase α to schizophrenia. 査読有り

    Takahashi N, Nielsen KS, Aleksic B, Petersen S, Ikeda M, Kushima I, Vacaresse N, Ujike H, Iwata N, Dubreuil V, Mirza N, Sakurai T, Ozaki N, Buxbaum JD, Sap J

    Biological psychiatry   70 巻 ( 7 ) 頁： 626 - 35   2011年10月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1016/j.biopsych.2011.06.016

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  32. Association analysis of the GDNF gene with methamphetamine use disorder in a Japanese population. 査読有り 国際誌

    Yoshimura T, Usui H, Takahashi N, Yoshimi A, Saito S, Aleksic B, Ujike H, Inada T, Yamada M, Uchimura N, Iwata N, Sora I, Iyo M, Ozaki N

    Progress in neuro-psychopharmacology & biological psychiatry   35 巻 ( 5 ) 頁： 1268 - 72   2011年7月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1016/j.pnpbp.2011.04.003

    PubMed

  33. Analysis of a purported SHANK3 mutation in a boy with autism: clinical impact of rare variant research in neurodevelopmental disabilities. 査読有り

    Kolevzon A, Cai G, Soorya L, Takahashi N, Grodberg D, Kajiwara Y, Willner JP, Tryfon A, Buxbaum JD

    Brain research   1380 巻   頁： 98 - 105   2011年3月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1016/j.brainres.2010.11.005

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  34. Haploinsufficiency of Gtf2i, a gene deleted in Williams Syndrome, leads to increases in social interactions. 査読有り

    Sakurai T, Dorr NP, Takahashi N, McInnes LA, Elder GA, Buxbaum JD

    Autism research : official journal of the International Society for Autism Research   4 巻 ( 1 ) 頁： 28 - 39   2011年2月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1002/aur.169

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  35. Linking oligodendrocyte and myelin dysfunction to neurocircuitry abnormalities in schizophrenia.

    Takahashi N, Sakurai T, Davis KL, Buxbaum JD

    Progress in neurobiology   93 巻 ( 1 ) 頁： 13 - 24   2011年1月

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  36. Haploinsufficiency of the autism-associated Shank3 gene leads to deficits in synaptic function, social interaction, and social communication. 査読有り

    Bozdagi O, Sakurai T, Papapetrou D, Wang X, Dickstein DL, Takahashi N, Kajiwara Y, Yang M, Katz AM, Scattoni ML, Harris MJ, Saxena R, Silverman JL, Crawley JN, Zhou Q, Hof PR, Buxbaum JD

    Molecular autism   1 巻 ( 1 ) 頁： 15   2010年12月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1186/2040-2392-1-15

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  37. Gene-wide association study between the methylenetetrahydrofolate reductase gene (MTHFR) and schizophrenia in the Japanese population, with an updated meta-analysis on currently available data. 査読有り 国際誌

    Yoshimi A, Aleksic B, Kawamura Y, Takahashi N, Yamada S, Usui H, Saito S, Ito Y, Iwata N, Inada T, Noda Y, Yamada K, Ozaki N

    Schizophrenia research   124 巻 ( 1-3 ) 頁： 216 - 22   2010年12月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1016/j.schres.2010.07.011

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  38. A genome-wide study reveals copy number variants exclusive to childhood obesity cases. 査読有り

    Glessner JT, Bradfield JP, Wang K, Takahashi N, Zhang H, Sleiman PM, Mentch FD, Kim CE, Hou C, Thomas KA, Garris ML, Deliard S, Frackelton EC, Otieno FG, Zhao J, Chiavacci RM, Li M, Buxbaum JD, Berkowitz RI, Hakonarson H, Grant SF

    American journal of human genetics   87 巻 ( 5 ) 頁： 661 - 6   2010年11月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1016/j.ajhg.2010.09.014

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  39. Strong synaptic transmission impact by copy number variations in schizophrenia. 国際誌

    Glessner JT, Reilly MP, Kim CE, Takahashi N, Albano A, Hou C, Bradfield JP, Zhang H, Sleiman PM, Flory JH, Imielinski M, Frackelton EC, Chiavacci R, Thomas KA, Garris M, Otieno FG, Davidson M, Weiser M, Reichenberg A, Davis KL, Friedman JI, Cappola TP, Margulies KB, Rader DJ, Grant SF, Buxbaum JD, Gur RE, Hakonarson H

    Proceedings of the National Academy of Sciences of the United States of America   107 巻 ( 23 ) 頁： 10584 - 9   2010年6月

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  40. Slc25a12 disruption alters myelination and neurofilaments: a model for a hypomyelination syndrome and childhood neurodevelopmental disorders.

    Sakurai T, Ramoz N, Barreto M, Gazdoiu M, Takahashi N, Gertner M, Dorr N, Gama Sosa MA, De Gasperi R, Perez G, Schmeidler J, Mitropoulou V, Le HC, Lupu M, Hof PR, Elder GA, Buxbaum JD

    Biological psychiatry   67 巻 ( 9 ) 頁： 887 - 94   2010年5月

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  41. Relationship of psychopathological symptoms and cognitive function to subjective quality of life in patients with chronic schizophrenia. 査読有り

    Tomida K, Takahashi N, Saito S, Maeno N, Iwamoto K, Yoshida K, Kimura H, Iidaka T, Ozaki N

    Psychiatry and clinical neurosciences   64 巻 ( 1 ) 頁： 62 - 9   2010年2月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1111/j.1440-1819.2009.02033.x

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  42. Extensive proteomic screening identifies the obesity-related NYGGF4 protein as a novel LRP1-interactor, showing reduced expression in early Alzheimer's disease.

    Kajiwara Y, Franciosi S, Takahashi N, Krug L, Schmeidler J, Taddei K, Haroutunian V, Fried U, Ehrlich M, Martins RN, Gandy S, Buxbaum JD

    Molecular neurodegeneration   5 巻   頁： 1   2010年1月

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  43. Common genetic variants on 5p14.1 associate with autism spectrum disorders.

    Wang K, Zhang H, Ma D, Bucan M, Glessner JT, Abrahams BS, Salyakina D, Imielinski M, Bradfield JP, Sleiman PM, Kim CE, Hou C, Frackelton E, Chiavacci R, Takahashi N, Sakurai T, Rappaport E, Lajonchere CM, Munson J, Estes A, Korvatska O, Piven J, Sonnenblick LI, Alvarez Retuerto AI, Herman EI, Dong H, Hutman T, Sigman M, Ozonoff S, Klin A, Owley T, Sweeney JA, Brune CW, Cantor RM, Bernier R, Gilbert JR, Cuccaro ML, McMahon WM, Miller J, State MW, Wassink TH, Coon H, Levy SE, Schultz RT, Nurnberger JI, Haines JL, Sutcliffe JS, Cook EH, Minshew NJ, Buxbaum JD, Dawson G, Grant SF, Geschwind DH, Pericak-Vance MA, Schellenberg GD, Hakonarson H

    Nature   459 巻 ( 7246 ) 頁： 528 - 33   2009年5月

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    記述言語：英語  

    DOI： 10.1038/nature07999

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  44. Linking white and grey matter in schizophrenia: oligodendrocyte and neuron pathology in the prefrontal cortex.

    Höistad M, Segal D, Takahashi N, Sakurai T, Buxbaum JD, Hof PR

    Frontiers in neuroanatomy   3 巻   頁： 9   2009年

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  45. No association between the protein tyrosine phosphatase, receptor-type, Z Polypeptide 1 (PTPRZ1) gene and schizophrenia in the Japanese population. 査読有り 国際誌

    Ito Y, Yamada S, Takahashi N, Saito S, Yoshimi A, Inada T, Noda Y, Ozaki N

    American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics   147B 巻 ( 7 ) 頁： 1013 - 8   2008年10月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1002/ajmg.b.30692

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  46. No association between tagging SNPs of SNARE complex genes (STX1A, VAMP2 and SNAP25) and schizophrenia in a Japanese population.

    Kawashima K, Kishi T, Ikeda M, Kitajima T, Yamanouchi Y, Kinoshita Y, Takahashi N, Saito S, Ohi K, Yasuda Y, Hashimoto R, Takeda M, Inada T, Ozaki N, Iwata N

    American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics   147B 巻 ( 7 ) 頁： 1327 - 31   2008年10月

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  47. The association of genotypic combination of the DRD3 and BDNF polymorphisms on the adhesio interthalamica and medial temporal lobe structures. 査読有り

    Takahashi T, Suzuki M, Tsunoda M, Kawamura Y, Takahashi N, Maeno N, Kawasaki Y, Zhou SY, Hagino H, Niu L, Tsuneki H, Kobayashi S, Sasaoka T, Seto H, Kurachi M, Ozaki N

    Progress in neuro-psychopharmacology & biological psychiatry   32 巻 ( 5 ) 頁： 1236 - 42   2008年7月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1016/j.pnpbp.2008.03.014

    PubMed

  48. A genetic association study of the FXYD domain containing ion transport regulator 6 (FXYD6) gene, encoding phosphohippolin, in susceptibility to schizophrenia in a Japanese population. 査読有り 国際誌

    Ito Y, Nakamura Y, Takahashi N, Saito S, Aleksic B, Iwata N, Inada T, Ozaki N

    Neuroscience letters   438 巻 ( 1 ) 頁： 70 - 5   2008年6月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1016/j.neulet.2008.04.010

    PubMed

  49. Relationship between three serotonin receptor subtypes (HTR3A, HTR2A and HTR4) and treatment-resistant schizophrenia in the Japanese population 査読有り

    Ji Xiaofei, Takahashi Nagahide, Saito Shinichi, Ishihara Ryoko, Maeno Nobuhisa, Inada Toshiya, Ozaki Norio

    NEUROSCIENCE LETTERS   435 巻 ( 2 ) 頁： 95 - 98   2008年4月

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    記述言語：日本語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1016/j.neulet.2008.01.083

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  50. Association between the brain-derived neurotrophic factor Val66Met polymorphism and brain morphology in a Japanese sample of schizophrenia and healthy comparisons. 査読有り

    Takahashi T, Suzuki M, Tsunoda M, Kawamura Y, Takahashi N, Tsuneki H, Kawasaki Y, Zhou SY, Kobayashi S, Sasaoka T, Seto H, Kurachi M, Ozaki N

    Neuroscience letters   435 巻 ( 1 ) 頁： 34 - 9   2008年4月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1016/j.neulet.2008.02.004

    PubMed

  51. Pathway-based association analysis of genome-wide screening data suggest that genes associated with the gamma-aminobutyric acid receptor signaling pathway are involved in neuroleptic-induced, treatment-resistant tardive dyskinesia.

    Inada T, Koga M, Ishiguro H, Horiuchi Y, Syu A, Yoshio T, Takahashi N, Ozaki N, Arinami T

    Pharmacogenetics and genomics   18 巻 ( 4 ) 頁： 317 - 23   2008年4月

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  52. Failure to replicate the association between NRG1 and schizophrenia using Japanese large sample.

    Ikeda M, Takahashi N, Saito S, Aleksic B, Watanabe Y, Nunokawa A, Yamanouchi Y, Kitajima T, Kinoshita Y, Kishi T, Kawashima K, Hashimoto R, Ujike H, Inada T, Someya T, Takeda M, Ozaki N, Iwata N

    Schizophrenia research   101 巻 ( 1-3 ) 頁： 1 - 8   2008年4月

    　詳細を見る

  53. An association study of tachykinin receptor 3 gene with schizophrenia in the Japanese population 査読有り

    Saito Shinichi, Takahashi Nagahide, Maeno Nobuhisa, Ito Yoshihito, Aleksic Branko, Usui Hinako, Iidaka Tetsuya, Inada Toshiya, Ozaki Norio

    NEUROREPORT   19 巻 ( 4 ) 頁： 471-473   2008年3月

    　詳細を見る

    記述言語：英語   掲載種別：研究論文（学術雑誌）  

  54. Genetic analysis of the gene coding for DARPP-32 (PPP1R1B) in Japanese patients with schizophrenia or bipolar disorder. 査読有り

    Yoshimi A, Takahashi N, Saito S, Ito Y, Aleksic B, Usui H, Kawamura Y, Waki Y, Yoshikawa T, Kato T, Iwata N, Inada T, Noda Y, Ozaki N

    Schizophrenia research   100 巻 ( 1-3 ) 頁： 334 - 41   2008年3月

    　詳細を見る

    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1016/j.schres.2007.10.028

    PubMed

  55. Gap junction, bipolar disorder and schizophrenia: Genetic association study 査読有り

    Aleksic Branko, Ikeda Masashi, Ishihara Ryoko, Takahashi Nagahide, Saito Sinichi, Matsumoto Atsushi, Inada Toshiya, Idaka Tetsuya, Iwata Nakao, Ozaki Norio

    NEUROSCIENCE RESEARCH   61 巻   頁： S219-S219   2008年

    　詳細を見る

    記述言語：英語   掲載種別：研究論文（学術雑誌）  

  56. Association of SOX10 with schizophrenia in the Japanese population 査読有り

    Maeno Nobuhisa, Takahashi Nagahide, Saito Shinichi, Ji Xiaofei, Ishihara Ryoko, Aoyama Nagisa, Branko Aleksic, Miura Hideki, Ikeda Masashi, Suzuki Tatsuyo, Kitajima Tsuyoshi, Yamanouchi Yoshio, Kinoshita Yoko, Iwata Nakao, Inada Toshiya, Ozaki Norio

    PSYCHIATRIC GENETICS   17 巻 ( 4 ) 頁： 227-231   2007年8月

    　詳細を見る

    記述言語：英語   掲載種別：研究論文（学術雑誌）  

  57. Gap junction coding genes and schizophrenia: a genetic association study 査読有り

    Aleksic Branko, Ishihara Ryoko, Takahashi Nagahide, Maeno Nobuhisa, Ji Xiaofei, Saito Shinichi, Inada Toshiya, Ozaki Norio

    JOURNAL OF HUMAN GENETICS   52 巻 ( 6 ) 頁： 498 - 501   2007年6月

    　詳細を見る

    記述言語：日本語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1007/s10038-007-0142-5

    Web of Science

    PubMed

  58. Association study between the transferrin gene and schizophrenia in the Japanese population.

    Maeno N, Takahashi N, Saito S, Ji X, Branko A, Ishihara R, Yoshida K, Inada T, Iidaka T, Ozaki N

    Neuroreport   18 巻 ( 5 ) 頁： 517 - 20   2007年3月

    　詳細を見る

  59. Gene-gene interaction analysis of personality traits in a Japanese population using an electrochemical DNA array chip analysis.

    Urata T, Takahashi N, Hakamata Y, Iijima Y, Kuwahara N, Ozaki N, Ono Y, Amano M, Inada T

    Neuroscience letters   414 巻 ( 3 ) 頁： 209 - 12   2007年3月

    　詳細を見る

▼全件表示

論文の先頭へ▲

書籍等出版物 4

  1. MADRSを使いこなす : SIGMAを用いたMADRS日本語版によるうつ病の臨床評価

    稲田 俊也, 岩本 邦弘, 高橋 長秀, 山本 暢朋

    じほう  2013年  （ ISBN:9784840744805 ）

    　詳細を見る

  2. SIGMAを用いたMADRS日本語版によるうつ病の臨床評価

    稲田 俊也, 岩本 邦弘, 高橋 長秀, 岩本 奈織野, 山本 暢朋

    じほう  2009年  （ ISBN:9784840739375 ）

    　詳細を見る

    記述言語：日本語

    CiNii Books

  3. Association between chromogranin A gene polymorphism and schizophrenia in the Japanese population

    高橋 長秀

    [s.n.]  2007年 

    　詳細を見る

    記述言語：英語

    CiNii Books

  4. SIGMAを用いたMADRS日本語版によるうつ病の臨床評価

    じほう  2009年 

書籍等出版物の先頭へ▲

MISC 6

  1. 慢性期統合失調症患者の主観的QOLに対する精神症状と認知機能の影響 招待有り

    富田顕旨, 高橋長秀, 齋藤真一, 前野信久, 岩本邦弘, 吉田契造, 木村宏之, 飯高哲也, 尾崎紀夫  

    精神神経学雑誌113 巻 ( 2 ) 頁： 135-143   2011年2月

    　詳細を見る

    記述言語：日本語   掲載種別：速報，短報，研究ノート等（学術雑誌）  

  2. Increased Expression of PTPRZ1 Leads to Delayed Oligodendrocyte Development and Evidence for Increased Dopamine Signaling in an Animal Model for Schizophrenia

    Nagahide Takahashi, Takeshi Sakurai, Mihaela Gazdoiu, Daniel English, Kenneth L. Davis, Joseph D. Buxbaum  

    BIOLOGICAL PSYCHIATRY65 巻 ( 8 ) 頁： 41S - 42S   2009年4月

    　詳細を見る

    記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：ELSEVIER SCIENCE INC  

    Web of Science

  3. FXYD6を標的とした統合失調症の病態解明

    伊藤 圭人, 中村 由嘉子, 高橋 長秀, 齋藤 真一, ブランコ・アレクシッチ, 吉田 契造, 飯高 哲也, 尾崎 紀夫  

    精神薬療研究年報 ( 41 ) 頁： 31 - 32   2009年3月

    　詳細を見る

    記述言語：日本語   出版者・発行元：(公財)先進医薬研究振興財団  

  4. Association study and copy number analysis of the DARPP-32 gene in bipolar disorder

    A. Yoshimi, N. Takahashi, Y. Kawamura, T. Kato, N. Kaneda, S. Saito, H. Usui, R. Ishihara, T. Inada, T. Yoshikawa, T. Kato, N. Iwata, Y. Noda, N. Ozaki  

    PSYCHIATRY AND CLINICAL NEUROSCIENCES62 巻 ( 1 ) 頁： S5 - S6   2008年2月

    　詳細を見る

    記述言語：英語   掲載種別：記事・総説・解説・論説等（学術雑誌）   出版者・発行元：BLACKWELL PUBLISHING  

    Web of Science

  5. Association analysis of MTHFR gene in schizophrenia

    Y. Kawamura, N. Takahashi, S. Saito, H. Usui, A. Yoshimi, Y. Ito, A. Branko, R. Ishihara, K. Yoshida, T. Iidaka, T. Inada, N. Iwata, Y. Noda, N. Ozaki  

    PSYCHIATRY AND CLINICAL NEUROSCIENCES62 巻 ( 1 ) 頁： S4 - S5   2008年2月

    　詳細を見る

    記述言語：英語   掲載種別：記事・総説・解説・論説等（学術雑誌）   出版者・発行元：BLACKWELL PUBLISHING  

    Web of Science

  6. 【統合失調症の分子精神医学】 NRG1と統合失調症

    池田 匡志, 高橋 長秀, 尾崎 紀夫, 岩田 仲生  

    分子精神医学7 巻 ( 4 ) 頁： 357 - 361   2007年10月

    　詳細を見る

    記述言語：日本語   出版者・発行元：(株)先端医学社  

    Neuregulin 1(NRG1)と統合失調症の関連は、Iceland人を対象とした連鎖解析、連鎖不平衡を用いた関連解析で報告されて以来、多くの追試がなされており、統合失調症の疾患感受性遺伝子の中で、最も有望なものの一つである。しかし、追試の結果は必ずしも一致しているわけではなく、有意差を報告する論文もある一方、関連は否定的とする報告もなされている。こうした不一致の原因には多くの要因が考えられるが、本稿では、民族差やサンプル数の問題などを取り上げながら、NRG1の統合失調症との関連を考察していきたい。(著者抄録)

▼全件表示

MISCの先頭へ▲

講演・口頭発表等 1

  1. Molecular and Cellular Evidence for Altered Myelination in Schizophrenia (symposium)

    Annual meeting of society of biological psychiatry  2009年 

講演・口頭発表等の先頭へ▲

科研費 7

  1. 無痛分娩をうけた母児の長期予後～懸念の払しょくからアドバンテージの探索へ

    研究課題/研究課題番号：21K19639  2021年7月 - 2023年3月

    科学研究費助成事業  挑戦的研究(萌芽)

    土屋 賢治, 秋永 智永子, 谷口 美づき, 成瀬 智, 朝羽 瞳, 伊東 宏晃, 高橋 長秀

    　 詳細を見る

    担当区分：研究分担者 

    硬膜外・脊髄くも膜下麻酔を用いて痛みを制御する「無痛分娩」は，日本では普及しない（5.2%，2018年）。わが国では，無痛分娩の長期予後への懸念，とりわけ「痛みに耐えなければ母親になれない」という信念や，児の発達にまつわる懸念が強い。そこで，1000名を超える新生児の10年追跡データをもとに，無痛分娩をうけた母児の長期予後をデータで明示し，これらの懸念を払拭できるかどうかを検討する。

  2. 産後うつ病の全ゲノム・メタボローム解析による病態解明とバイオマーカーの開発

    研究課題/研究課題番号：21K07479  2021年4月 - 2024年3月

    科学研究費助成事業  基盤研究(C)

    高橋 長秀, 富田 博秋

    　 詳細を見る

    担当区分：研究代表者 

    配分額：4160000円 （ 直接経費：3200000円 、 間接経費：960000円 ）

    産後を含む周産期うつ病は頻度が高く、妊産婦には苦痛とQOL低下、ひいては自死をもたらし、児の養育環境の悪化も引き起こすために、早期発見・要介入群の同定や適切な治療法の確立が喫緊の課題である。本研究では、妊産婦前向きコホート参加者のDNAおよび血漿を用いて①ゲノムワイド関連解析による発症リスクを高める遺伝子多型とパスウェイの同定②先行研究を利用したPolygenic risk score解析によるコホート参加者の産後うつ病に対する遺伝的リスクの算出と、発症に対する診断能・経過予測能の検討③末梢血のメタボローム解析による疾患の発症と重症度に関連する代謝物の同定とバイオマーカーとしての評価を行う。

  3. 新規の病態解明を企図した自閉スペクトラム症多発家系のロングリードシークエンス

    研究課題/研究課題番号：21H02848  2021年4月 - 2024年3月

    科学研究費助成事業  基盤研究(B)

    木村 大樹, Aleksic Branko, 高橋 長秀

    　 詳細を見る

    担当区分：研究分担者 

    自閉スペクトラム症(ASD)の発症には遺伝要因の関与が指摘されているが、これまでのゲノム解析手法では、一部の症例にしかASD発症脆弱性ゲノム変異が同定されない。近年、ロングリードシークエンス技術が登場し、これまで同定が困難であった小さな規模のゲノム変異や、繰り返し配列の差異の検出が可能となった。この技術を用いることで、創薬や新規診断法に結びつくような、ASD発症への新しいメカニズムの解明を目指す。

  4. 発達精神医学におけるプレシジョン・メディシンの展開

    研究課題/研究課題番号：19H03582  2019年4月 - 2022年3月

    科学研究費助成事業  基盤研究(B)

    土屋 賢治, 原 武史, 岩渕 俊樹, 西村 倫子, 奥村 明美, 原田 妙子, 桑原 斉, 高橋 長秀

    　 詳細を見る

    担当区分：研究分担者 

    浜松母と子の出生コホート（HBC Study，N=1258）のデータを利用して，自閉スペクトラム症（ASD）および注意欠如・多動症（ADHD）と関連する個別化変数を探索する。その個別化変数が満たす条件とは，
    ①ASDまたはADHDの診断と関連し，②ASDまたはADHDの中間表現型と関連し，③ASDまたはADHDの予後と関連する，の3つである。
    「診断・中間表現型・予後などの臨床的変数を正しく予測する『個別化変数』の利用」という要素に焦点を当て，この領域の代表的な疾患である自閉スペクトラム症（ASD）と注意欠如・多動症（ADHD）の個別化変数の抽出を目指す。
    HBC Studyは，地域代表性のある1258名の新生児とその保護者から構成される出生コホートであり，頻回かつ詳細な神経発達の評価（粗大・微細運動，視覚受容，受容・表出言語）および神経発達症の評価（ASDの行動特性を反映するAutism Diagnostic Observation Scale［6歳］およびADHDの行動特性を反映するADHD-RS［6および8歳］）を完了した。2020年度は，HBC Study全対象者の口腔粘膜細胞から抽出したDNAを用いて，ゲノムワイドなSNP解析（ジャポニカアレイV2）を行うとともに，全対象者のASDに対するPolygenic risk score（PRS）をPsychiatric Genomics Consortiumをリファレンスとして，ADHDに対するPRSを1000 Genome Project reference panel phase 3をリファレンスとして，計算した。
    解析対象者は，ゲノムデータを有し，6および8歳の計測を完了した876名である。解析の結果，ASDに対するPRSは，6歳におけるASDの行動特性と強く関連し，また18カ月における粗大運動スコア・受容言語と負の関連を示した。一方，ADHDに対するPRSは，8歳におけるADHDの行動特性と弱い関連しか示さなかった。一方，ADHDと臨床的な関連の深いナルコレプシーに対するPRSを計算し，ADHDの行動特性との関連を検討したところ，ADHDの不注意特性，多動衝動特性のいずれに対しても強い関連が明らかとなった。同様の関連はASDの行動特性には見られなかった。
    プロトコルに沿った情報収集，解析を進めた。また，成果をJAMA Network Open誌に投稿し，受理された。さらに，新しいアイディア，すなわち，ナルコレプシーと注意欠如多動症（ADHD）の臨床的類似性に着目した解析を進め，両者の遺伝的背景の共通性を見出した。この成果をTranslational Psychiatry誌に投稿し，受理された。
    最終年度のプロトコルに沿った情報収集，解析を進める。

  5. Genetics anlysis of schizophrenia

    2004年 - 2008年

    JST Basic Research Programs (Core Research for Evolutional Science and Technology :CREST) 

    　 詳細を見る

    資金種別：競争的資金

  6. 統合失調症，自閉症の遺伝統計学的研究

    2004年 - 2008年

    ＪＳＴ戦略的創造研究推進制度（研究チーム型） （戦略的基礎研究推進事業：ＣＲＥＳＴ） 

    　 詳細を見る

    資金種別：競争的資金

  7. 統合失調症，自閉症の病態生理研究

    　 詳細を見る

    資金種別：競争的資金

▼全件表示

科研費の先頭へ▲
 

担当経験のある科目 (本学) 2

  1. 児童精神医学

    2021

  2. 児童精神医学

    2020

担当経験のある科目 (本学)の先頭へ▲

担当経験のある科目 (本学以外) 1

  1. 児童精神医学

    （浜松医科大学）

    　詳細を見る

    科目区分：大学院専門科目 

担当経験のある科目 (本学以外)の先頭へ▲