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Association of genetic polymorphisms with drug-response and personality in mood disorders

Research Project

Project/Area Number 10670923
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Psychiatric science
Research InstitutionFujita Health University

Principal Investigator

OZAKI Norio  Fujita Health University School of Medicine, Department of Psychiatry, Professor, 医学部・精神医学教室, 教授 (40281480)

Co-Investigator(Kenkyū-buntansha) IWATA Nakao  Fujita Health University School of Medicine, Department of Psychiatry, Associate Professor, 医学部・精神医学教室, 講師 (60312112)
SATO Tetsuya  Fujita Health University School of Medicine, Department of Psychiatry, Associate Professor, 医学部・精神医学教室, 講師 (00187212)
永津 俊治  藤田保健衛生大学, 総合医科学研究所, 教授 (40064802)
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2000: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1999: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1998: ¥1,200,000 (Direct Cost: ¥1,200,000)
KeywordsMOOD DISOREDERS / GENE / DRUG-RESPONSE / PERSONALITY / BREEDING EXPERIENCE / 免疫学
Research Abstract

Lifetime prevalence of mood disorders is estimated about 15% and mood disorders cause a serious social loss and a high suicide rate. There are many treatment-resistant cases with mood disorders although the treatment by antidepressants and mood stabilizers has been established. The pathophysiology of this disorders has not yet unknown, thus the elucidation of the pathophysiology is required to establish the prevention and treatment of this condition. According to the clinical genetic studies, such as the family study, the twin study, and the adopted study, genetic factors are hypothesized to participate in the etiology of mood disorders. In addition, abnormal monoamines in patients with mood disorders and monoaminergic mechanisms of psychotropic drugs suggest that abnormality of monoamines participates in the pathophysiology of mood disorders. These two points mentioned above lead to the monoaminergic genetic studies of mood disorders. No reproducible result, however, has acquired. One … More of the reasons for the obstacle is that mood disorders are etiologically heterogeneous disorders. Therefore, we have to grasp the family history, the response to psychotropic drugs, the personality, the breeding experience and the clinical information in order to elucidate the pathophysiology. In addition, by progress of molecular biology, we can search for monoaminergic molecular genetic mechanisms that is used to be impossible. Thus, we started to examine the monoaminergic molecular genetic background in patients with mood disorders after we obtained their drug-response, other biological data, their breeding experience, personality and the clinical features.
We examined the personality using the TC1 in depression. As a result, the severity of depression showed the positive correlation with Harm Avoidance, and the negative correlation with Self-Directedness and Cooperativeness. Furthermore, good responders became close to normal values after an antidepressant treatment, but bad responders did not change. On the other hand, on the breeding experience using PBI, patients with depression and OCD showed a low caring of parents and a high protection of a mother. In addition, patients with atopic dermatitis had high Harm Avoidance with TCI and no characteristics with PBI.On the other hand, according to the molecular genetic study of seasonal affective disorder, the 5HTT polymorphism had the association with the disease, but the 5-HT1a, 1b, 1d, 2a, 2c do not.
We are going to continue the molecular genetic research to obtain a marker for the drug response and open the road to the development of a new drug. Furthermore, we are carrying out researches to aim at goals as follows. 1) Developing a tool for early discovery of depression. 2) Frequency of mood disorders and an environment factor in laborers and patient with general medical conditions. 3) Effectiveness of cognitive behavior therapy for depression. Less

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] Kusunoki K,Sato T,Taga C,Yoshida Y,Komori K,Narita T,Hirano S,Iwata N,Ozak N: "Low novelty-seeking differentiated obsessive-compulsive disorder from major depression."Acta Psychiatr Scand. 101. 403-405 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Narita T,Sato T,Hirano S,Goto M,Sakado K,Uehara T: "Parental child-rearing behavior as measured by the Parental Bonding Instrument in a Japanese population."J Affect Disord. 57. 229-234 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Lappalainen J, Long JC, Eggert M, Ozaki N, Robin RW, Brown GL, Naukkarinen H, Virkkunen M, Linnoila M, Goldman D: "Linkage of antisocial alcoholism to the serotonin 5-HT1B receptor gene in 2 populations."Archives of General Psychiatry.. 55 (11). 989-94 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Gosenthal NE, Mazzanti CM, Barnett RL, Hardin TA, Turner EH, Lam GK, Ozaki N., Goldman D: "Role of serotonin transporter promoter repeat length polymorphism (5-HTTLPR) in seasonality and seasonal affective disorder"Molecular Psychiatry. 3 (2). 175-7 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kusunoki K, Ozaki N, Sawada M, Sato T, Hirano S, Narita T: "Serum levels of dihydroneopterin and soluble cytokine receptors in major depression."Pteridines. 10. 24-26 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Lappalainen J, Long J, Virkkunen M, Ozaki N, Goldman D, Linnoila M: "HTR2C Cys23Ser polymorphism in relation to CSF monoamine metabolite concentrations and DSM-III-R psychiatric diagnoses."Biol Psychiatry. 46. 821-826 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Sher L, Goldman D, Ozaki N, Rosenthal N: "The role of genetic factors in the etiology of seasonal affective disorder and seasonality."Journal of Affective Disorder. 53. 203-210 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hibiya M, Ichinose H, Ozaki N, Fujita K, Nishimoto T, Yoshikawa T, Asano Y, Nagatsu T: "Normal value and age-dependent changes in GTP cyclohydrase I activity in stimulated mononuclear blood cells measured by high-performance liquid chromatography."Journal of Chromatography B. 740. 35-42 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kusunoki K, Sato T, Taga C, Yoshida Y, Komori K, Narita T, Hirano S, Iwata N, Ozaki N: "Low novelty-seeking differentiated obsessive-compulsive disorder from major depression."Acta Psychiatr Scand. 101. 403-405 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kusunoki K,Sato T,Taga C,Yoshida Y,Komori K,Narita T,Hirano S,Iwata N,Ozaki: "Lownovelty-seeking differentiated obsessive-compulsive disorder from major depression"Acta Psychiatr Scand. 101. 403-405 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Narita T,Sato T,Hirano S,Goto M,Sakado K,Uehara T: "Parental child-rearing behavior as measured by the Parental Bonding Instrument in a Japanese population."J Affect Disord. 57. 229-234 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Lappalainen J, Long J, Virkkunen M, Ozaki N, Goldman D, Linnoila M: "HTR2C Cys23Ser polymorphism in relation to CSF monoamine metabolite concentrations and DSM-III-R psychiatric diagnoses"Biol Psychiatry. 46. 821-826 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kusunoki K, Ozaki N, Sawada M, Sato T, Hirano S, Narita T: "Serum levels of dihydroneopterin and soluble cytokine receptors in major depression"Pteridines. 10. 24-26 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Sher L, Goldman D, Ozaki N, Rosenthal N: "The role of genetic factors in the etiology of seasonal affective disorder and seasonality"Journal of Affective Disorder. 53. 203-210 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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