Relationship between brain volume and the gene polymorphisms of catechol-O-methyltransferase and norepinephrine transporter in treatment-naïve major depressive disorder: Voxel-based morphometry

• Project/Area Number: 25461858
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Radiation science
• Research Institution: University of Occupational and Environmental Health, Japan
• Principal Investigator: KOROGI Yukunori 産業医科大学, 医学部, 教授 (60195691)
• Co-Investigator(Kenkyū-buntansha): KAKEDA Shingo 産業医科大学, 医学部, 講師 (30352313) ; NAKAMURA Jun 産業医科大学, 医学部, 非常勤講師 (40148804) ; MORIYA Junji 産業医科大学, 医学部, 助教 (50412656) ; KATSUKI Asuka 産業医科大学, 医学部, 助教 (60566488) ; YOSHIMURA Reiji 産業医科大学, 医学部, 教授 (90248568)
• Research Collaborator: OGASAWARA Atsushi ; MURAKAMI Yu ; MIYATA Mari ; ABE Osamu ; WATANABE Keita ; UEDA Issei ; IGATA Ryohei ; SUGIMOTO Koichiro
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2015: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2013: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: 大うつ病性障害 / 遺伝子多型 / 拡散テンソル画像 / 脳MR統計画像解析

Outline of Final Research Achievements

We assessed associations of genetic variations in catechol-O-methyltransferase (COMT) and norepinephrine transporter (NET) with brain volume in major depressive disorder (MDD) using VBM analysis of brain MRI. We recruited 30 first-episode, treatment-naïve MDD patients and 48 healthy subjects matched for age and gender; they were divided by the COMT/NET genotypes. Effects of the genotype and the genotype-diagnosis interaction in relation to brain morphology in the each group were evaluated using a VBM. In the healthy subjects, interacting functional variants in COMT affected gray matter regional volume; Val/Val individuals had smaller volume in the bilateral caudate and the posterior cingulate cortex compared to Val/Met individuals. In the MDD cases, the COMT genotype affected volume reduction in the caudate. A significant NET genotype (G1287A) - diagnosis interaction was found in the left dorsolateral prefrontal cortex, and the polymorphism of the NET gene was associated with

Research Products

• [Journal Article] Relationship between G1287A of the NET Gene Polymorphisms and Brain Volume in Major Depressive Disorder: A Voxel-Based MRI Study. (2016)
  • Author(s): Ueda I., Kakeda S., Watanabe K., Yoshimura R., Kishi T., Abe O., Ide S., Moriya J., Katsuki A., Hori H., Iwata N., Nakamura J., Korogi Y.
  • Journal Title: PLoS ONE Volume: 11 Issue: 3 Pages: e0150712-e0150712
  • DOI: 10.1371/journal.pone.0150712
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] RELATIONSHIP BETWEEN THE CORTICAL THICKNESS AND SERUM CORTISOL LEVELS IN DRUG-NAÏVE, FIRST-EPISODE PATIENTS WITH MAJOR DEPRESSIVE DISORDER: A SURFACE-BASED MORPHOMETRIC STUDY. (2015)
  • Author(s): Liu X, Kakeda S, Watanabe K, Yoshimura R, Abe O, Ide S, Hayashi K, Katsuki A, Umeno-Nakano W, Watanabe R, Ueda I, Moriya J, Nakamura J, Korogi Y.
  • Journal Title: Depress Anxiety. Volume: 32 Issue: 9 Pages: 702-8
  • DOI: 10.1002/da.22401
  • Peer Reviewed
• [Journal Article] Relationship between the catechol-O-methyl transferase Val108/158Met genotype and brain volume in treatment-naive major depressive disorder: Voxel-based morphometry analysis (2015)
  • Author(s): Watanabe K, Kakeda S, Yoshimura R, Abe O, Ide S, Hayashi K, Katsuki A, Umene-Nakano W, Watanabe R, Nakamura J, Korogi Y
  • Journal Title: Psychiatry Res Volume: 233 Pages: 481-7
  • Peer Reviewed
• [Journal Article] Relationship between a BDNF gene polymorphism and the brain volume in treatment-naive patients with major depressive disorder: A VBM analysis of brain MRI (2015)
  • Author(s): Ide S, Kakeda S, Watanabe K, Yoshimura R, Abe O, Hayashi K, Ueda I, Kishi T, Katsuki A, Umene-Nakano W, Iwata N, Nakamura J, Korogi Y.
  • Journal Title: Psychiatry Res. Volume: 30 Issue: 2 Pages: 120-4
  • DOI: 10.1016/j.pscychresns.2015.05.016
  • Peer Reviewed
• [Presentation] Relationship between the hippocampal shape abnormality and serum cortisol levels in first-episode and drug naïve major depressive disorder (2015)
  • Author(s): Keita Watanabe, Shingo Kakeda, Rieko Watanabe, Xiaodan Liu, Kenji Hayashi , Asuka Katsuki , Osamu Abe, Reiji Yoshimura, Yukunori Korogi
  • Organizer: 第43回日本磁気共鳴医学会
  • Place of Presentation: 東京都文京区 東京ドームホテル
  • Year and Date: 2015-09-10
• [Presentation] Relationship between gene polymorphism, neurotransmitter, and brain MR imaging in major depressive disorder (2015)
  • Author(s): Yukunori Korogi
  • Organizer: American Society of Neuroradiology 2015
  • Place of Presentation: 米国シカゴ市 Sheraton Chicago Hotel & Towers
  • Year and Date: 2015-04-27
  • Int'l Joint Research / Invited
• [Presentation] Susceptibility changes in normal-appearing basal ganglia in patients with neuropsychiatric systemic lupus erythematosus: evaluation of quantitative susceptibility mapping (2014)
  • Author(s): Atsushi Ogasawara, Shingo Kakeda, Keita Watanabe, Issei Ueda, Yu Murakami, Junji Moriya, Satoru Ide, Koichiro Futatsuya, Toru Sato, Kazuyoshi Saito, Yoshiya Tanaka, Tian Liu, Yi Wang, Yukunori Korogi
  • Organizer: Radiological Society of North America
  • Place of Presentation: 米国シカゴ市 McCormick place
  • Year and Date: 2014-12-26
• [Presentation] Relationship between white matter integrity and serum cortisol levels in drug-naïve major depressive disorder patients: a diffusion tensor imaging study using tract-based spatial statistics (2014)
  • Author(s): Xiaodan Liu, Keita Watanabe, Shingo Kakeda, Reiji Yoshimura, Osamu Abe, Satoru Ide, Kenji Hayashi, Asuka Katsuki, Wakako Umene-Nakano, Rieko Watanabe, Issei Ueda, Jun Nakamura, Yukunori Korogi
  • Organizer: American Society of Neuroradiology
  • Place of Presentation: カナダモントリオール市 Palais des congrés de Montreal
  • Year and Date: 2014-05-20
• [Presentation] Catechol-O-methyl transferase Val108/158Met genotype influences the caudate volume in healthy subjects: A voxel-based morphometry study at 3T MRI. (2014)
  • Author(s): Keita Watanabe, Shingo Kakeda, Reiji Yoshimura, Osamu Abe, Satoru Ide, Rieko Watanabe, Asuka Katsuki, Wakako Umene-Nakano, Jun Nakamura, Yukunori Korogi
  • Organizer: 日本医学放射線学会
  • Place of Presentation: 横浜市 パシフィコ横浜
  • Year and Date: 2014-04-13