Testing the dimensional model between schizophrenia and schizotypy

• Project/Area Number: 23791372
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Psychiatric science
• Research Institution: National Center of Neurology and Psychiatry
• Principal Investigator: HORI Hiroaki 独立行政法人国立精神・神経医療研究センター, 神経研究所疾病研究第三部, 流動研究員 (10554397)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 統合失調症 / 統合失調型パーソナリティ / 臨床 / 認知機能 / 遺伝子多型 / CACNA1C / 神経内分泌

Research Abstract

By investigating similarities and differences between schizophrenia and schizotypal personality in terms of genes and cognition, this study aimed to provide evidence that contributes to elucidating the pathophysiology of schizophrenia. A series of investigations have revealed that schizotypal traits in healthy individuals and those in patients with mood disorder show a cognitive profile similar to the one seen in schizophrenia and that a genetic polymorphism within CACNA1C, a gene that has been shown to be associated with mood disorders and schizophrenia, affects cognition in schizophrenia.

Research Products

• [Journal Article] Relationship of temperament and character with cortisol reactivity to the combined dexamethasone/CRH test in depressed outpatients (2013)
  • Author(s): Hori H
  • Journal Title: Journal of Affective Disorders Volume: 147 Issue: 1-3 Pages: 128-136
  • DOI: 10.1016/j.jad.2012.10.022
  • Peer Reviewed
• [Journal Article] Identification of single nucleotide polymorphisms regulating peripheral blood mRNA expression with genome-wide significance: an eQTL study in the Japanese population (2013)
  • Author(s): Sasayama D, Hori H, Nakamura S
  • Journal Title: PLos One. Volume: 8 Issue: 1 Pages: e54967-e54967
  • DOI: 10.1371/journal.pone.0054967
  • NAID: 120007110614
  • Peer Reviewed
• [Journal Article] Moderating effect of schizotypy on the relationship between smoking and neurocognition (2013)
  • Author(s): Hori H, Matsuo J, Teraishi T
  • Journal Title: Eur Psychiatry Volume: (in press) Issue: 8 Pages: 457-462
  • DOI: 10.1016/j.eurpsy.2012.09.002
  • Peer Reviewed
• [Journal Article] Increased cerebrospinal fluid interleukin-6 levels in patients with schizophrenia and those with major depressive disorder. (2013)
  • Author(s): Sasayama D
  • Journal Title: J Psychiatr Res. Volume: 47 Issue: 3 Pages: 401-6
  • DOI: 10.1016/j.jpsychires.2012.12.001
  • Peer Reviewed
• [Journal Article] Multimodal image analysis of sensorimotor gating in healthy women (2013)
  • Author(s): Ota M
  • Journal Title: Brain Research Volume: 1499 Pages: 61-68
  • DOI: 10.1016/j.brainres.2012.12.044
  • Peer Reviewed
• [Journal Article] Association of cognitive performance with interleukin-6 receptor Asp358Ala polymorphism in healthy adults (2012)
  • Author(s): Sasayama D, Hori H, Teraishi T
  • Journal Title: J Neural Transm. Volume: 119 Issue: 3 Pages: 313-318
  • DOI: 10.1007/s00702-011-0709-3
  • NAID: 120007110620
  • Peer Reviewed
• [Journal Article] Relationships between season of birth, schizotypy, temperament, character and neurocognition in a non-clinical population (2012)
  • Author(s): Hori H, Teraishi T, Sasayama D
  • Journal Title: Psychiatry Res. Volume: 195 Issue: 1-2 Pages: 69-75
  • DOI: 10.1016/j.psychres.2011.07.028
  • Peer Reviewed
• [Journal Article] Elevated cortisol level and cortisol/DHEAS ratio in schizophrenia as revealed by low-dose dexamethasone suppression test (2012)
  • Author(s): Hori H, Teraishi T, Sasayama D
  • Journal Title: The Open Neuropsychopharmacology Journal Volume: 5 Pages: 18-24
  • URL: http://benthamscience.com/open/toneuroppj/articles/V005/18TONEUROPPJ.pdf
  • Peer Reviewed
• [Journal Article] More severe impairment of manual dexterity in bipolar disorder compared to unipolar major depression (2012)
  • Author(s): Sasayama D, Hori H, Teraishi T
  • Journal Title: J Affect Disord Volume: 136 Issue: 3 Pages: 1047-1052
  • DOI: 10.1016/j.jad.2011.11.031
  • NAID: 120007110622
  • Peer Reviewed
• [Journal Article] Association between the functional polymorphism (C3435T) of the gene encoding P-glycoprotein (ABCB1) and major depressive disorder in the Japanese population (2012)
  • Author(s): Fujii T, Ota M, Hori H, Sasayama D, Hattori K, Teraishi T, Yamamoto N, Hashikura M, Tatsumi M, Higuchi T, Kunugi H.
  • Journal Title: J Psychiatr Res Volume: 46(4) Issue: 4 Pages: 555-9
  • DOI: 10.1016/j.jpsychires.2012.01.012
  • Peer Reviewed
• [Journal Article] Possible impact of ADRB3 Trp64Arg polymorphism on BMI in patients with schizophrenia (2012)
  • Author(s): Sasayama D, Hori H, Teraishi T
  • Journal Title: Prog Neuropsychopharmacol Biol Psychiatry Volume: 38 Issue: 2 Pages: 341-344
  • DOI: 10.1016/j.pnpbp.2012.05.007
  • NAID: 120007110621
  • Peer Reviewed
• [Journal Article] Schizotypy and genetic loading for schizophrenia impact upon neuropsychological status in bipolar II and unipolar major depressive disorders (2012)
  • Author(s): Hori H, Matsuo J, Teraishi T
  • Journal Title: J Affect Disord Volume: 142 Issue: 1-3 Pages: 225-232
  • DOI: 10.1016/j.jad.2012.04.031
  • Peer Reviewed
• [Journal Article] Schizotypal trait in healthy women is associated with a shift away from dextrality on a spatial motor control task, but not on a force control task (2012)
  • Author(s): Hori H, Teraishi T, Sasayama D
  • Journal Title: Psychiatry Res. Volume: 200 Issue: 2-3 Pages: 629-634
  • DOI: 10.1016/j.psychres.2012.05.032
  • Peer Reviewed
• [Journal Article] C^<13>-phenylalanine breath test detects altered phenylalanine kinetics in schizophrenia patients (2012)
  • Author(s): Toshiya Teraishi, Yuji Ozeki, Hiroaki Hori, Daimei Sasayama, Shuichi Chiba, Noriko Yamamoto, Haruko Tanaka, Yoshimi Iijima, Junko Matsuo, Yumiko Kawamoto, Yukiko Kinoshita, Kotaro Hattori, Miho Ota, Masahiro Kajiwara, Sumio Terada, Teruhiko Higuchi, Hiroshi Kunugi
  • Journal Title: Translational Psychiatry Volume: 2 Issue: 5 Pages: e119-e119
  • DOI: 10.1038/tp.2012.48
  • Peer Reviewed
• [Journal Article] The efficacy of pramipexole, a dopamine receptor agonist, as an adjunctive treatment in treatment-resistant depression: an open-label trial (2012)
  • Author(s): Hori H
  • Journal Title: The Scientific World Journal Volume: 2012 Pages: 372474-372474
  • DOI: 10.1100/2012/372474
  • Peer Reviewed
• [Journal Article] Effects of the CACNA1C risk allele on neurocognition in patients with schizophrenia and healthy individuals (2012)
  • Author(s): Hori H, Yamamoto N, Fujii T, Teraishi T, Sasayama D, Matsuo J, Kawamoto Y, Kinoshita Y, Ota M, Hattori K, Tatsumi M, Arima K, Kunugi H.
  • Journal Title: Sci Rep Volume: 2 Issue: 1 Pages: 634-634
  • DOI: 10.1038/srep00634
  • Peer Reviewed
• [Journal Article] Glutamatergic changes in the cerebral white matter associated with schizophrenic exacerbation (2012)
  • Author(s): Ota M
  • Journal Title: Acta Psychiatrica Scandinavica Volume: 126 Issue: 1 Pages: 72-78
  • DOI: 10.1111/j.1600-0447.2012.01853.x
  • Peer Reviewed
• [Journal Article] Kazutaka Shimoda Pharmachotherapeutic determinants for QTc interval prolongation in Japanese patients with mood disorder (2012)
  • Author(s): Hiroaki Okayasu, Yuji Ozeki, Kumiko Fujii, Yumiko Takano, Yoshinori Saeki, Hiroaki Hori, Minoru Horie, Teruhiko Higuchi, Hiroshi Kunugi
  • Journal Title: Pharmacopsychiatry Volume: (in press) Issue: 07 Pages: 279-83
  • DOI: 10.1055/s-0032-1308969
  • Peer Reviewed
• [Journal Article] Negative correlation between cerebrospinal fluid oxytocin levels and negative symptoms of male patients with schizophrenia. (2012)
  • Author(s): Sasayama D
  • Journal Title: Schizophr Res. Volume: 139 Issue: 1-3 Pages: 201-6
  • DOI: 10.1016/j.schres.2012.06.016
  • Peer Reviewed
• [Journal Article] 視床下部-下垂体-副腎系とうつ病：最近の展開 (2012)
  • Author(s): 功刀 浩
  • Journal Title: 日本神経精神薬理学雑誌 Volume: 4 Pages: 203-210
• [Journal Article] Discrimination of schizophrenic females from healthy women using multiple structural brain measures obtained with voxel-based morphometry. (2012)
  • Author(s): Ota M, et al,
  • Journal Title: Psychiatry and Clinical Neurosciences, Volume: 66(7): Issue: 7 Pages: 611-7
  • DOI: 10.1111/j.1440-1819.2012.02397.x
  • Peer Reviewed
• [Journal Article] The 3rd Schizophrenia International Research Society Conference, 14-18 April 2012, Florence, Italy: summaries of oral sessions (2012)
  • Author(s): Abbs B
  • Journal Title: Schizophrenia Research Volume: 141 Issue: 1 Pages: e1-e24
  • DOI: 10.1016/j.schres.2012.07.024
• [Journal Article] Blood CADPS2ΔExon3 expression is associated with intelligence and memory in healthy adults (2012)
  • Author(s): Hattori K
  • Journal Title: Biol Psychol Volume: 89 Issue: 1 Pages: 117-22
  • DOI: 10.1016/j.biopsycho.2011.09.017
  • Peer Reviewed
• [Journal Article] Association of interleukin-1β genetic polymorphisms with cognitive performance in elderly females without dementia (2011)
  • Author(s): Sasayama D, Hori H, Teraishi T
  • Journal Title: J Hum Genet. Volume: 56 Issue: 8 Pages: 613-616
  • DOI: 10.1038/jhg.2011.56
  • NAID: 10030660649
  • Peer Reviewed
• [Journal Article] Association of plasma IL-6 and soluble IL-6 receptor levels with the Asp358Ala polymorphism of the IL-6 receptor gene in schizophrenic patients (2011)
  • Author(s): Sasayama D, Wakabayashi C, Hori H
  • Journal Title: J Psychiatr Res. Volume: 45 Issue: 11 Pages: 1439-1444
  • DOI: 10.1016/j.jpsychires.2011.06.003
  • Peer Reviewed
• [Journal Article] Modulation of cortisol responses to the DEX/CRH test by polymorphisms of the interleukin-1beta gene in healthy adults (2011)
  • Author(s): Sasayama D, Hori H, Iijima Y
  • Journal Title: Behav Brain Funct Volume: 7 Issue: 1 Pages: 23-23
  • DOI: 10.1186/1744-9081-7-35
  • NAID: 120007110615
  • Peer Reviewed
• [Journal Article] Support for association between the Ser205Leu polymorphism of p75(NTR) and major depressive disorder (2011)
  • Author(s): Fujii T, Ota M, Hori H, Sasayama D, Hattori K, Teraishi T, Yamamoto N, Hashikura M, Tatsumi M, Higuchi T, Kunugi H.
  • Journal Title: J Hum Genet Volume: 56(11) Issue: 11 Pages: 806-9
  • DOI: 10.1038/jhg.2011.107
  • Peer Reviewed
• [Journal Article] Attitudes toward schizophrenia in the general population, psychiatric staff, physicians, and psychiatrists: a web-based survey in Japan (2011)
  • Author(s): Hori H, Richards M, Kawamoto Y, Kunugi H
  • Journal Title: Psychiatry Research Volume: 186 Issue: 2-3 Pages: 183-189
  • DOI: 10.1016/j.psychres.2010.08.019
  • Peer Reviewed
• [Journal Article] Hiroshi Kunugi Schizotypal personality in healthy adults is related to blunted cortisol responses to the combined dexamethasone/corticotropin-releasing hormone test (2011)
  • Author(s): Hiroaki Hori, Toshiya Teraishi, Yuji Ozeki, Kotaro Hattori, Daimei Sasayama, Jyunko Matsuo, Yumiko Kawamoto, Yukiko Kinoshita, Teruhiko Higuchi
  • Journal Title: Neuropsychobiology Volume: 1 Issue: 4 Pages: 232-41
  • DOI: 10.1159/000322146
  • Peer Reviewed
• [Journal Article] Difference in Temperament and Character Inventory scores between depressed patients with bipolar II and unipolar major depressive disorders (2011)
  • Author(s): Sasayama D, Hori H, Teraishi T, Hattori K, Ota M, Matsuo J, Kawamoto Y, Kinoshita Y, Hashikura M, Koga N, Okamoto N, Sakamoto K, Higuchi T, Amano N, Kunugi H
  • Journal Title: Journal of Affective Disorders Volume: 132 Issue: 3 Pages: 319-324
  • DOI: 10.1016/j.jad.2011.03.009
  • Peer Reviewed
• [Journal Article] Poor sleep is associated with exaggerated cortisol response to the combined dexamethasone/CRH test in a non-clinical population (2011)
  • Author(s): Hori H, Teraishi T, Sasayama D, Ozeki Y, Matsuo J, Kawamoto Y, Kinoshita Y, Hattori K, Higuchi T, Kunugi H
  • Journal Title: Journal of Psychiatric Research Volume: 45 Issue: 9 Pages: 1257-1263
  • DOI: 10.1016/j.jpsychires.2011.04.001
  • Peer Reviewed
• [Journal Article] Expression of Ca^<2+>-dependent activator protein for secretion 2 is increased in the brains of schizophrenic patients (2011)
  • Author(s): Hattori K
  • Journal Title: Prog Neuropsychopharmacol Biol Psychiatry Volume: 35 Issue: 7 Pages: 1738-43
  • DOI: 10.1016/j.pnpbp.2011.05.004
  • Peer Reviewed
• [Journal Article] Modulation of cortisol responses to the DEX/CRH test by polymorphisms of the interleukin-1beta gene in healthy adults (2011)
  • Author(s): Sasayama D, Hori H, Iijima Y, Teraishi T, Hattori K, Ota M, Fujii T, Higuchi T, Amano N, Kunugi H.
  • Journal Title: Behav Brain Funct Volume: 7 Issue: 1 Pages: 23-23
  • DOI: 10.1186/1744-9081-7-23
  • NAID: 120007110615
  • Peer Reviewed
• [Presentation] 大うつ病性障害におけるパーソナリティはコルチゾール反応性を予測する:デキサメタゾン/CRHテストによる検討 (2012)
  • Author(s): 堀弘明
  • Organizer: 第34回日本生物学的精神医学会
  • Place of Presentation: 神戸国際会議場、神戸
  • Year and Date: 2012-09-29
• [Presentation] A multifaceted approach to understanding the pathophysiology of schizophrenia from the perspective of schizotypal personality (2012)
  • Author(s): Hori H
  • Organizer: The 2012 Annual Meeting of Taiwanese Society of Biological Psychiatry and Neuropsychopharmacology
  • Place of Presentation: Sheraton Grande Taipei Hotel, Taipei, Taiwan(招待講演)
  • Year and Date: 2012-09-22
• [Presentation] The bipolar risk allele at CACNA1C impacts on neurocognition in patients with schizophrenia (2012)
  • Author(s): Hori H
  • Organizer: The 2nd Meeting of East Asian Bipolar Forum
  • Place of Presentation: Centennial Hall Kyushu University School of Medicine, Fukuoka, Japan
  • Year and Date: 2012-09-07
• [Presentation] Personality dimensions in major depressive disorder predict cortisol reactivity to the combined dexamethasone/CRH test (2012)
  • Author(s): Hori H
  • Organizer: The 28th CINP World Congress of Neuropsychopharmacology
  • Place of Presentation: Stockholmsmassan, Stockholm, Sweden
  • Year and Date: 2012-06-06
• [Presentation] Schizotypy and genetic loading for schizophrenia impact upon neuropsychological status in bipolar II and unipolar major depressive disorders (2012)
  • Author(s): Hori H
  • Organizer: The 67th Annual Scientific Meeting of the Society of Biological Psychiatry
  • Place of Presentation: Sheraton Philadelphia Downtown Hotel, Philadelphia, Pennsylvania, USA
  • Year and Date: 2012-05-04
• [Presentation] Schizotypy and genetic loading for schizophrenia impact upon neuropsychological status in bipolar II and unipolar major depressive disorders (2012)
  • Author(s): Hori H
  • Organizer: The 3rd Biennial Schizophrenia International Research Conference
  • Place of Presentation: Firenze Fiera, Florence, Italy
  • Year and Date: 2012-04-17
• [Presentation] 統合失調症の遺伝負因と統合失調型パーソナリティは、双極II型障害・大うつ病性障害患者の認知機能に影響を与える (2012)
  • Author(s): 堀弘明
  • Organizer: 第7回日本統合失調症学会
  • Place of Presentation: 愛知県産業労働センター, 名古屋
  • Year and Date: 2012-03-16
• [Presentation] Schizotypy and genetic loading for schizophrenia impact upon neuropsychological status in bipolar II and unipolar major depressive disorders (2012)
  • Author(s): Hori H
  • Organizer: The 67th Annual Scientific Meeting of the Society of Biological Psychiatry
  • Place of Presentation: Sheraton Philadelphia Downtown Hotel &#8211; Philadelphia, Pennsylvania, USA
• [Presentation] Personality dimensions in major depressive disorder predict cortisol reactivity to the combined dexamethasone/CRH test (2012)
  • Author(s): Hori H
  • Organizer: The 28th CINP World Congress of Neuropsychopharmacology
  • Place of Presentation: Stockholmsm&auml;ssan, Stockholm, Sweden
• [Presentation] A multifaceted approach to understanding the pathophysiology of schizophrenia from the perspective of schizotypal personality (2012)
  • Author(s): Hori H
  • Organizer: The 2012 Annual Meeting of Taiwanese Society of Biological Psychiatry and Neuropsychopharmacology
  • Place of Presentation: Sheraton Grande Taipei Hotel, Taipei, Taiwan
  • Invited
• [Presentation] 大うつ病性障害におけるパーソナリティはコルチゾール反応性を予測する：デキサメタゾン/CRHテストによる検討 (2012)
  • Author(s): 堀 弘明
  • Organizer: 第34回日本生物学的精神医学会
  • Place of Presentation: 神戸国際会議場, 神戸
• [Presentation] 統合失調症と統合失調型パーソナリティの連続性の検証 (2011)
  • Author(s): 堀弘明
  • Organizer: 第31回日本精神科診断学会
  • Place of Presentation: 信州大学医学部附属病院外来棟、松本
  • Year and Date: 2011-11-19
• [Presentation] 薬物負荷試験を用いた統合失調症と統合失調症型パーソナリティにおける視床下部-下垂体-副腎系機能の検討 (2011)
  • Author(s): 堀弘明
  • Organizer: 第6回日本統合失調症学会
  • Place of Presentation: 札幌コンベンションセンター、札幌
  • Year and Date: 2011-07-19
• [Presentation] 視床下部-下垂体-副腎系とうつ病スペクトラム (2011)
  • Author(s): 堀弘明
  • Organizer: 第30回躁うつ病の薬理・生化学的研究懇話会
  • Place of Presentation: 京都ガーデンパレス、京都
  • Year and Date: 2011-07-15
• [Presentation] Elevated cortisol levels and cortisol/dehydroepiandrosterone ratio in schizophrenia as revealed by the dexamethasone suppression test (2011)
  • Author(s): Hori H
  • Organizer: 13th International Congress on Schizophrenia Research
  • Place of Presentation: The BROADMOOR - Colorado Springs, Colorado, USA
  • Year and Date: 2011-04-04
• [Presentation] Elevated cortisol levels and cortisol/dehydroepiandrosterone ratio in schizophrenia as revealed by the dexamethasone suppression test (2011)
  • Author(s): Hori H, Teraishi T, Sasayama D, Ishikawa M, Higuchi T, Kunugi H
  • Organizer: 13th International Congress on Schizophrenia Research
  • Place of Presentation: The BROADMOOR - Colorado Springs, Colorado
• [Presentation] 視床下部-下垂体-副腎系とうつ病スペクトラム (2011)
  • Author(s): 堀弘明, 寺石俊也, 篠山大明, 松尾淳子, 川本由実子, 木下裕紀子, 服部功太郎, 樋口輝彦, 功刀浩
  • Organizer: 第30回躁うつ病の薬理・生化学的研究懇話会
  • Place of Presentation: 京都ガーデンパレス, 京都
• [Presentation] 薬物負荷試験を用いた統合失調症と統合失調症型パーソナリティにおける視床下部-下垂体-副腎系機能の検討 (2011)
  • Author(s): 堀弘明, 太田深秀, 寺石俊也, 篠山大明, 尾関祐二, 石川正憲, 服部功太郎, 功刀浩
  • Organizer: 第6回日本統合失調症学会
  • Place of Presentation: 札幌コンベンションセンター, 札幌
• [Presentation] 統合失調症と統合失調型パーソナリティの連続性の検証 (2011)
  • Author(s): 堀弘明, 寺石俊也, 篠山大明, 松尾淳子, 川本由実子, 木下裕紀子、功刀浩
  • Organizer: 第31回日本精神科診断学会
  • Place of Presentation: 信州大学医学部附属病院外来棟, 松本
• [Book] 「視床下部-下垂体-副腎系とうつ病スペクトラム」. 気分障害の薬理・生化学. 編集:躁うつ病の薬理・生化学的研究懇話会 (2012)
  • Author(s): 堀弘明、功刀浩
  • Publisher: 医薬ジャーナル社,編集:小山 司, 樋口 輝彦
• [Book] 「ミルタザピンのバイオマーカーに対する影響」. ミルタザピンのすべて (2012)
  • Author(s): 堀弘明、功刀浩
  • Publisher: 先端医学社
• [Book] 「視床下部-下垂体-副腎系機能検査法と精神疾患」. 精神疾患診断のための脳形態・機能検査法 (2012)
  • Author(s): 堀弘明、功刀浩
  • Publisher: 新興医学出版社、編集:三國雅彦, 福田正人, 功刀浩
• [Book] モデルで考える精神疾患 (2012)
  • Author(s): ピーター・タイラー、デレック・スタインバーグ
  • Total Pages: 392
  • Publisher: 星和書店,堀弘明(翻訳)
• [Book] 精神疾患診断のための脳形態・機能検査法 (2012)
  • Author(s): 三國雅彦, 福田正人, 功刀浩（編）
  • Total Pages: 230
  • Publisher: 新興医学出版社
• [Book] 気分障害の薬理・生化学 (2012)
  • Author(s): 躁うつ病の薬理生化学的研究懇話会（編）
  • Total Pages: 335
  • Publisher: 医薬ジャーナル社
• [Book] ミルタザピンのすべて (2012)
  • Author(s): 小山司, 樋口輝彦（編）
  • Total Pages: 202
  • Publisher: 先端医学社
• [Book] モデルで考える精神疾患 (2012)
  • Author(s): ピーター・タイラー, デレック・スタインバーグ (著), 堀弘明 (翻訳)
  • Total Pages: 392
  • Publisher: 星和書店
• [Remarks] 独立行政法人国立精神・神経医療研究センター神経研究所疾病研究第三部 webページ
  • URL: http://www.ncnp.go.jp/nin/guide/r3/index.html
• [Remarks] 独立行政法人国立精神・神経医療研究センター 神経研究所 疾病研究第三部
  • URL: http://www.ncnp.go.jp/nin/guide/r3/
• [Remarks]
  • URL: http://www.ncnp.go.jp/nin/guide/r3/index.html