Research on the pathophysiology of panic disorder focusing on asymmetry of brain function

• Project/Area Number: 16K10187
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Mie University
• Principal Investigator: TANII HISASHI 三重大学, 保健管理センター, 教授 (40346200)
• Project Period (FY): 2016-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: パニック症 / 非対称性 / 遺伝子多型 / 拡散テンソル画像 / FreeSurfer解析 / 合併症 / small-world network / ライフイベント / 前頭葉機能 / 環境因子 / 遺伝的因子

Outline of Final Research Achievements

In addition to gene polymorphism analysis and psychosocial tests for panic disorder patients group and healthy subjects, we studied the analyses by adding brain function image data. Analysis of endophenotypes such as personality traits and brain volume obtained by psychological tests in panic disease suggested an asymmetric genetic involvement in the complications of panic disorder. Particularly, the associations of the complications (bipolar disorder, depression and agoraphobia) and genetic factor such as serotonin transporter gene polymorphisms have been shown.

Academic Significance and Societal Importance of the Research Achievements

生涯有病率が2-5％とされるパニック症の中核症状であるパニック発作は一般人口での生涯有病率は約20％とも言われている。パニック症では広場恐怖など社会生活上の障害を伴う疾患を併発するため、その病態解明は今日の重要な課題である。本研究においては神経線維束による脳内ネットワーク、脳層や脳微細構造などの非対称性に着目し、それらと疾患特異的な性差や合併症の有無、ライフイベントなどの心理社会的因子、遺伝的因子の関与について解析した。その結果、パニック症に特有の非対称性が示唆された。

Research Products

• [Journal Article] Shared Trans-ancestry Genetic Etiology between Panic Disorder and Anxiety Disorders. (2021)
  • Author(s): Ohi K, Otowa T, Shimada M, Sugiyama S, Muto Y, Tanahashi S, Kaiya H, Nishimura F, Sasaki T, Tanii H, Shioiri T
  • Journal Title: Psychiatry Clin Neurosci. Volume: 75 Issue: 6 Pages: 1-2
  • DOI: 10.1111/pcn.13214
  • Peer Reviewed / Open Access
• [Journal Article] Internet-based Individualized Cognitive Behavioral Therapy for Shift Work Sleep Disorder (Empowered by Wellbeing Prediction): A Pilot Study Protocol. (2021)
  • Author(s): Ito-Masui A, Sakamoto R, Yu H,, Sano A, Motomura E, Tanii H, Sakano S, Esumi R, Imai H, Shimaoka M
  • Journal Title: J JMIR Res Protoc. Volume: 10(3) Issue: 3 Pages: e24799-e24799
  • DOI: 10.2196/24799
  • Peer Reviewed / Open Access
• [Journal Article] Association of serotonin transporter gene (5-HTTLPR/rs25531) polymorphism with comorbidities of panic disorder. (2021)
  • Author(s): Tanahashi S, Tanii H, Konishi Y Otowa T, Sasaki T, Tochigi M, Okazaki Y, Kaiya H, Okada M
  • Journal Title: Neuropsychobiology. Volume: 80 Issue: 4 Pages: 1-9
  • DOI: 10.1159/000512699
  • Peer Reviewed
• [Journal Article] Shared transethnic genetic basis of panic disorder and psychiatric and related intermediate phenotypes. (2021)
  • Author(s): Ohi K, Otowa T, Shimada M, Sugiyama S, Muto Y, Tanahashi S, Kaiya H, Nishimura F, Sasaki T, Tanii H, Shioiri T
  • Journal Title: Eur Neuropsychopharmacol Volume: 42 Pages: 87-96
  • DOI: 10.1016/j.euroneuro.2020.11.003
  • Peer Reviewed
• [Journal Article] Sensitivity to gene dosage and gene expression affects genes with copy number variants observed among neuropsychiatric diseases (2020)
  • Author(s): aria Yamasaki, Takashi Makino, Seik-Soon Khor et al
  • Journal Title: BMC Medical Genomics Volume: Mar 29 Issue: 1 Pages: 55-55
  • DOI: 10.1186/s12920-020-0699-9
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Do postpartum anxiety and breastfeeding self-efficacy and bonding at early postpartum predict postpartum depression and the breastfeeding method? (2020)
  • Author(s): Minamida T, Iseki A, Sakai H, Imura M, Okano T, Tanii H
  • Journal Title: Infant Ment Health J Volume: 41(5) Issue: 5 Pages: 662-676
  • DOI: 10.1002/imhj.21866
  • Peer Reviewed / Open Access
• [Journal Article] Do postpartum anxiety and breastfeeding self-efficacy and bonding at early postpartum predict postpartum depression and the breastfeeding method? (2020)
  • Author(s): Minamida T, Iseki A, Sakai H, Imura M, Okano T, Tanii H
  • Journal Title: Infant Mental Health Journal Volume: 41
  • Peer Reviewed / Open Access
• [Journal Article] Shared genetic etiology between anxiety disorders and psychiatric and related intermediate phenotypes. (2019)
  • Author(s): Ohi K, Otowa T, Shimada M, Sasaki T, Tanii H.
  • Journal Title: Psychological Medicine Volume: - Issue: 4 Pages: 692-704
  • DOI: 10.1017/s003329171900059x
  • Peer Reviewed
• [Journal Article] 神経症：総論（概念と分類） (2019)
  • Author(s): 谷井久志
  • Journal Title: 精神科（精神科診療マニュアル、特別増刊号） Volume: 35(Suppl 1) Pages: 133-138
• [Journal Article] Prospective HLA-A*31:01 screening and the incidence of carbamazepine-induced cutaneous adverse reactions in Japanese. (2018)
  • Author(s): Mushiroda T, Takahashi Y, Onuma T, Yamamoto Y, Kamei T, Hoshida T, Takeuchi K, Otsuka K, Okazaki M, Watanabe M, Kanemoto K, Oshima T, Watanabe A, Minami S, Saito K, Tanii H et al; GENCAT Study Group.
  • Journal Title: JAMA Neurology Volume: 75 Issue: 7 Pages: 842-849
  • DOI: 10.1001/jamaneurol.2018.0278
  • Peer Reviewed
• [Journal Article] 不安症と双極性障害,自閉スペクトラム症の合併 不安症と双極性障害の併存率 (2018)
  • Author(s): 谷井久志
  • Journal Title: 精神科 Volume: 33
• [Journal Article] An epigenome-wide methylation study of healthy individuals with or without depressive symptoms. (2018)
  • Author(s): Shimada M, Otowa T, Miyagawa T, Umekage T, Kawamura Y, Bundo M, Iwamoto K, Ikegame T, Tochigi M, Kasai K, Kaiya H, Tanii H, Okazaki Y, Tokunaga K, Sasaki T. An epigenome-wide methylation study of healthy individuals with or without depressive symptoms.
  • Journal Title: J Hum Genet Volume: 63 Issue: 3 Pages: 319-326
  • DOI: 10.1038/s10038-017-0382-y
  • Peer Reviewed / Open Access
• [Journal Article] A genome-wide association study identifies two novel susceptibility loci and trans population polygenicity associated with bipolar disorder. (2017)
  • Author(s): Ikeda M, Shimasaki A, Takahashi A,et al.
  • Journal Title: Mol Psychiatry Volume: in press Issue: 3 Pages: 1-9
  • DOI: 10.1038/mp.2016.259
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Epigenome-wide association study of DNA methylation in panic disorder (2017)
  • Author(s): Shimada-Sugimoto, M., T. Otowa, T. Miyagawa, T. Umekage, Y. Kawamura, M. Bundo, K. Iwamoto, M. Tochigi, K. Kasai, H. Kaiya, H. Tanii, Y. Okazaki, K. Tokunaga and T. Sasaki
  • Journal Title: Clinical Epigenetics Volume: 9 Issue: 1 Pages: 6-6
  • DOI: 10.1186/s13148-016-0307-1
  • Peer Reviewed / Open Access
• [Journal Article] Evaluation of polygenic risks for narcolepsy and essential hypersomnia (2016)
  • Author(s): Yamasaki M, Miyagawa T, Toyoda H, Khor SS, Liu X, Kuwabara H, Kano Y, Shimada T, Sugiyama T, Nishida H, Sugaya N, Tochigi M, Otowa T, Okazaki Y, Kaiya H, Kawamura Y, Miyashita A, Kuwano R, Kasai K, Tanii H, Sasaki T, Honda Y, Honda M, Tokunaga K
  • Journal Title: Journal of Human Genetics Volume: 61(10) Issue: 10 Pages: 873-878
  • DOI: 10.1038/jhg.2016.65
  • NAID: 40020966185
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Polymorphisms in the TMEM132D region are associated with panic disorder in HLA-DRB1*13:02-negative individuals of a Japanese population. (2016)
  • Author(s): Shimada-Sugimoto M, Otowa T, Miyagawa T, Khor S-S, Omae Y, Toyo-oka L, Sugaya N, Kawamura Y, Umekage T, Miyashita A, Kuwano R, Kaiya H, Kasai K, Tanii H, Okazaki Y, Tokunaga K, Sasaki T
  • Journal Title: Human Genome Variation Volume: 3 Issue: 1 Pages: 16001-16001
  • DOI: 10.1038/hgv.2016.1
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Auditory change-related cerebral responses and personality traits (2016)
  • Author(s): Tanahashi M., Motomura E., Inui K. et al.
  • Journal Title: Neuroscience Research Volume: 103 Pages: 34-39
  • DOI: 10.1016/j.neures.2015.08.005
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Candidate Genes in Panic Disorder: Meta-Analyses of 23 Common Variants in Major Anxiogenic Pathways. (2015)
  • Author(s): Howe AS, Buttenschon H, Bani-Fatemi A, Maron E, Otowa T, Erhardt A, Binder EB, Gregersen N, Domschke K, Reif A, Shlik J, Koks S, Kawamura Y, Miyashita A, Kuwano R, Tokunaga K, Tanii H, Sasaki T, Smoller JW, De Luca1 V
  • Journal Title: Molecular Psychiatry Volume: 20 Issue: 5 Pages: 1-15
  • DOI: 10.1038/mp.2015.138
  • Peer Reviewed / Int'l Joint Research
• [Presentation] パニック症の脳画像解析と不安特性との関連について (2020)
  • Author(s): 谷井久志、木下義也、大須賀一輝、杉田直樹、棚橋俊介、小西喜昭、大井一高、城山隆
  • Organizer: NPBPPP 2020 合同年会 in SENDAI、第50回日本神経精神薬理学会年会・第42回日本生物学的精神医学会年会・第4回日本精神薬学会総会・学術集会合同年会.
• [Presentation] 大学生における睡眠と不安や人格特性、精神的健康度との関連 (2019)
  • Author(s): 谷井久志、高橋宣貴、棚橋俊介
  • Organizer: 第41回全国大学メンタルヘルス学会総会
• [Presentation] Shared Genetic Etiology between Anxiety Disorders and Psychiatric and Related Intermediate Phenotypes (2019)
  • Author(s): 大井一貴、音羽健司、嶋多真穂子、佐々木司、谷井久志
  • Organizer: 第11回日本不安症学会学術大会.
• [Presentation] Shared Genetic Etiology between Anxiety Disorders and Psychiatric and Related Intermediate Phenotypes. (2019)
  • Author(s): 大井一貴、音羽健司、嶋多真穂子、佐々木司、谷井久志
  • Organizer: 第11回日本不安症学会学術大会
• [Presentation] パニック症における脳内ネットワーク障害とBDNF val66Met遺伝子多型との関連 - MRI拡散テンソル画像を用いた検討 (2017)
  • Author(s): 谷井久志、江尻直弥、城山隆、小西喜昭、岡田元宏、貝谷久宣、音羽健司、佐々木司、岡崎祐士
  • Organizer: 第39回日本生物学的精神医学会
• [Presentation] パニック症における併存症とセロトニントランスポーター遺伝子多型の関連について (2016)
  • Author(s): 棚橋俊介、谷井久志、林隆昌、小西喜昭、岡田元宏、貝谷久宣、音羽健司、佐々木司、岡崎祐士
  • Organizer: 第38回日本生物学的精神医学会
  • Place of Presentation: 福岡国際会議場（福岡県・福岡市）
  • Year and Date: 2016-09-08
• [Book] パニック発作特定用語の解説 日本臨床75巻6月号 別冊精神科症候群II（第２版） (2017)
  • Author(s): 谷井久志
  • Total Pages: 5
  • Publisher: 日本臨床社
• [Book] 日本臨床75巻6月号 別冊精神科症候群II（第２版） (2017)
  • Author(s): 谷井久志
  • Publisher: 日本臨床社
• [Book] 精神科研修ノート第２版 (2016)
  • Author(s): 谷井久志
  • Total Pages: 640
  • Publisher: 診断と治療社