| Project/Area Number |
05454310
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Psychiatric science
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
TORU Michio Professor, Dept.of Neuropsychiatry, Tokyo Medical and Dental Univ.School of Medicine, 医学部, 教授 (20013972)
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| Co-Investigator(Kenkyū-buntansha) |
WATANABE Akiko Technician, ditto, 医学部, 技官 (40210992)
KURUMAJI Akeo Lecturer, ditto, 医学部, 助手 (00251504)
SHIBUYA Haruo Associate Professor, ditto, 医学部, 助教授 (10158959)
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| Project Period (FY) |
1993 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥5,400,000 (Direct Cost: ¥5,400,000)
Fiscal Year 1994: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1993: ¥3,300,000 (Direct Cost: ¥3,300,000)
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| Keywords | Schizophrenia / Dopamine D2 receptor / Dopamine D2 receptor gene / S311C variant / Negative symptoms / アミノ酸ミスセンス変異 |
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| Research Abstract |
This study attempted to examine the heterogeneity of schizophrenia by using a missense variant (S311C) found in the dopamine D2 receptor gene (DRD2). Case-control studies in 156 schizophrenics and 300 controls on an association of a molecular variant of S311C was significantly in schizophrenics (9%) compared with controls (3.7%). Schizophrenics with S311C variant showed less severe negative symptoms than those wihtout. The second association study was dose in expanded numbers of schizophrenics (292) and controls (579). In schizophrenics, significantly higher frequency of those with S311C (8.9%) was again found compared with controls (4.1%). The frequency of S331C in the schizophrenics without negative symptoms (17.1%) was remarkably higher than the controls (p<0.00001). Schizophrenics with S311C were mainly subtyped into paranoid type and a very few into disorganized type. Examination of the courses of the patients by using Bleuler's clssification of the course of schizophrenia revealed that there were significantly fewer cases who showed simple course to deterioration in those with S311C than those without.
Thus, these data suggest that the missense variant, S311C,found in DRD2 might not be a risk factor but might be one of the genetic factors which modulate the course of the disease by affecting the response of the patients to antipsychotic drug treatment.
The pharmacological properties of receptor proteins with S311C transfected in the cultured cells are now under investigation comparing with those of wild type.
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