Advertisement
Original article| Volume 40, ISSUE 12, P1209-1217, December 15, 1996

Polymorphisms of dopamine D2-like (D2, D3, and D4) receptors in schizophrenia

DOI:https://doi.org/10.1016/0006-3223(95)00673-7
Polymorphisms of dopamine D2-like (D2, D3, and D4) receptors in schizophrenia
Previous ArticleObstetric complications and age-related changes in brain morphology in schizophrenia
Next ArticleA study of the potential confounding effects of diet, caffeine, nicotine and lorazepam on the stability of plasma and urinary homovanillic acid levels in patients with schizophrenia
      This paper is only available as a PDF. To read, Please Download here.
      The result of most association studies and linkage analyses have suggested a negative association between schizophrenia and D2-like (D2, D3, and D4) receptor polymorphisms. Although the polymorphisms of the D2-like receptor in themselves may not account for the etiology of schizophrenia, they can contribute to the severity of the symptoms. Thus, we studied the associations between the polymorphisms and their combinations, and the vulnerability of schizophrenics. Fragments of the D2-like receptor genes were amplified by means of the polymerase chain reaction, and the polymorphisms were identified by the restriction fragment length polymorphism and single-stranded conformation polymorphism methods. There were no statistically significant differences in the polymorphisms and their combinations between schizophrenics and controls. Schizophrenics with D4E1(A1/A2), which contains 2 and 1 tandem repeats of a 12-base-pair sequence in exon 1, had a lower total positive symptom score before medication than schizophrenics with D4E1(A1/A1). There was no association between the polymorphisms and negative symptoms.

      Key Words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Biological Psychiatry
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Register: Create an account
      Institutional Access: Sign in to ScienceDirect

      References

        • American Psychiatric Association
        4th ed. Diagnostic and Statistical Manual of Mental Disorders. American Psychiatric Press, Malmö, Sweden1994
        • Arinami T
        • Itokawa M
        • Enguchi H
        • et al.
        Association of dopamine D2 recpetor molecular variant with schizophrenia.
        Lancet. 1994; 343: 703-704
        • Asherson P
        • Williams N
        • Roberts E
        • McGuffin M
        • Owen M
        DRD2 Ser311/Cys311 polymorphism in schizophrenia.
        Lancet. 1994; 343: 1045
        • Bunzow JR
        • Van Tol HHM
        • Grandy DK
        • et al.
        Cloning and expression of a rat D2 dopamine receptor cDNA.
        Nature. 1988; 336: 783-787
        • Catalano M
        • Nobile M
        • Novelli E
        • Smeraldi E
        Use of polymerase chain reaction and denaturing gradient three exons of dopamine D2 receptor gene in schizophrenic and delusional patients.
        Neuropsychobiology. 1992; 26: 1-3
        • Catalano M
        • Nobile M
        • Novelli E
        • Nöthen M
        • Smeraldi E
        Distribution of a novel mutation in the first exon of the human dopamine D4 receptor gene in psychotic patients.
        Biol Psychiatry. 1993; 34: 459-464
        • Coon H
        • Byerley W
        • Holik J
        • et al.
        Linkage analysis of schizophrenia with five dopamine receptor genes in nine pedigrees.
        Am J Hum Genet. 1993; 52: 327-334
        • Crocq M-A
        • Mant R
        • Asherson P
        • et al.
        Association between schizophrenia and homozygosity at the dopamine D3 receptor gene.
        J Med Genet. 1992; 29: 858-860
        • Crow TJ
        Molecular pathology of schizophrenia: More than one disease process?.
        Br Med J. 1980; 280: 66-68
        • Crow TJ
        Positive and negative schizophrenic symptoms and the role of dopamine.
        Br J Psychiatry. 1980; 137: 383-386
        • Crow TJ
        Positive and negative schizophrenic symptoms and the role of dopamine.
        Br J Psychiatry. 1981; 139: 251-254
        • Dearry A
        • Gingrich JA
        • Falardeau P
        • Fremeau Jr, RT
        • Bates MD
        • Caron MG
        Molecular cloning and expression of the gene for a human D1 dopamine receptor.
        Nature. 1990; 347: 72-76
        • Endicott J
        • Spitzer RL
        A diagnostic interview: The Schedule for Affective Disorders and Schizophrenia.
        Arch Gen Psychiatry. 1978; 35: 837-844
        • Gejman PV
        • Ram A
        • Gelernter J
        • et al.
        No structural mutation in the dopamine D2 receptor gene in alcoholism or schizophrenia.
        JAMA. 1994; 271: 204-208
        • Gill M
        • McGuffin P
        • Parfitt E
        • et al.
        A linkage study of schizophrenia with DNA markers from the long arm of chromosome 11.
        Psychol Med. 1993; 23: 27-44
        • Giros B
        • Sokoloff P
        • Martres M-P
        • Riou J-F
        • Emorine LJ
        • Schwarz J-C
        Alternative splicing directs the expression of two D2 dopamine receptor isoforms.
        Nature. 1989; 342: 923-926
        • Giros B
        • Martes M-P
        • Sokoloff P
        • Schwartz J-C
        Clonage du gene du recepteur dopaminergique D3 humain et identification de son chromosome.
        Comples Rendu Acad Sci Paris. 1990; 311: 501-508
        • Giros B
        • Martres M-P
        • Polon C
        • Sokoloff P
        • Schwartz J-C
        Shorter variants of the D3 dopamine receptor produced through various patterns of alternative splicing.
        Biochem Biophys Res Commun. 1991; 176: 1584-1592
        • Gottesman II,
        Schizophrenia Genesis.
        WH Freeman and Company, Washington, DC1991
        • Grandy DK
        • Marchionni MA
        • Makam H
        • et al.
        Cloning of the cDNA and gene for a human D2 dopamine receptor.
        in: Proc Natl Acad Sci USA. 86. 1989: 9762-9766
        • Hallmayer J
        • Maier W
        • Schwab S
        • et al.
        No evidence of linkage between the dopamine D2 receptor gene and schizophrenia.
        Psychiatry Res. 1994; 53: 203-215
        • Hongyo T
        • Buzard GS
        • Calvert RJ
        • Weghorst CM
        “Cold SSCP”: A simple, rapid and non-radioactive method for optimized single-stranded conformation polymorphism analysis.
        Nucl Acids Res. 1993; 21: 3637-3642
        • Jones CT
        • Morris S
        • Moffoot A
        • D St. Clair
        • Brock DJ
        Screening Alzheimer's disease patients for mutations in the amyloid precursor protein gene.
        Mol Cell Probes. 1993; 7: 161-165
        • Jonsson E
        • Lannfelt L
        • Sokoloff P
        • Schwartz J-C
        • Sedvall G
        Lack of association between schizophrenia and alleles in the dopamine D3 receptor gene.
        Acta Psychiatr Scand. 1993; 87: 345-349
      25. (Translated to Japanese by Yamada H, Masui K, Kikumoto K, Tokyo: Seiwa Shoten Publishers, 1991.)
        • Kay SR
        • Opler LA
        • Fiszbein A
        Positive and Negative Syndrome Scale (PANSS) Rating Manual. Multi-Health Systems Inc, New York1991
        • Kebabian JK
        • Calne DB
        Multiple receptors for dopamine.
        Nature. 1979; 277: 93-96
        • Lannfelt L
        • Sokoloff P
        • Martres MP
        • et al.
        Amino acid substitution in the dopamine D3 receptor as a useful polymorphism for investigating psychiatric disorders.
        Psychiatr Genet. 1992; 2: 249-256
        • Lichter JB
        • Barr CL
        • Kennedy JL
        • Van Tol HHM
        • Kidd K
        • Livak KJ
        A hypervariable segment in the human dopamine D4 (DRD4) gene.
        Hum Mol Genet. 1993; 2: 767-773
        • Macciardi F
        • Petronis A
        • Van Tol HHM
        • et al.
        Analysis of the D4 dopamine receptor gene variant in an Italian schizophrenia kindred.
        Arch Gen Psychiatry. 1994; 51: 288-293
        • Moises HW
        • Gelernter J
        • Giuffra LA
        • et al.
        No linkage between a D2 dopamine receptor gene region and schizophrenia.
        Arch Gen Psychiatry. 1991; 48: 643-647
        • Monsma Jr, FJ
        • McVittie LD
        • Gerien CR
        • Mahan LC
        • Sibley DR
        Multiple D2 dopamine receptors produced by alternative RNA splicing.
        Nature. 1989; 342: 926-929
        • Nanko S
        • Hattori M
        • Ikeda K
        • Sasaki T
        • Kazamatsuri H
        • Kuwata S
        Dopamine D4 receptor polymorphism and schizophrenia.
        Lancet. 1993; 341: 689-690
        • Nanko S
        • Hattori M
        • Dai XY
        • Fukuda R
        • Kazamatsuri H
        DRD2 Ser311/Cys311 polymorphism in schizophrenia.
        Lancet. 1994; 343: 1044-1045
        • Nöthen MM
        • Korner J
        • Lannfelt L
        • et al.
        Lack of association between schizophrenia and alleles of the dopamine D1, D2, D3 and D4 receptor loci.
        Psychiatr Genet. 1993; 3: 89-94
        • Nöthen MM
        • Wildenauer D
        • Cichon S
        • et al.
        Dopamine D2 receptor molecular variant and schizophrenia.
        Lancet. 1994; 343: 1301-1302
        • Ohara K
        • Haga K
        • Berstein G
        • Haga T
        • Ichiyama A
        • Ohara K
        The interaction between D-2 dopamine receptors and GTP-binding proteins.
        Mol Pharmacol. 1988; 33: 290-296
        • Ohara K
        • Ulpian C
        • Seeman P
        • Sunahara RK
        • Van Tol HHM
        • Niznik HB
        Schizophrenia: Dopamine D1 receptor sequence is normal, but has DNA polymorphisms.
        Neuropsychopharmacology. 1993; 8: 131-135
        • O'Malley KL
        • Harmon S
        • Tang L
        • Todd RD
        The rat dopamine D4 receptor: Sequence, gene structure, and demonstration of expression in the cardiovascular system.
        New Biologist. 1992; 4: 137-146
        • Rao PA
        • Pickar D
        • Gejman PV
        • Ram A
        • Gershon ES
        • Gelernter J
        Allelic variation in the D4 dopamine receptor (DRD4) gene does not predict response to clozapine.
        Arch Gen Psychiatry. 1994; 51: 912-917
        • Sarkar G
        • Kapelner S
        • Grandy DK
        • et al.
        Direct sequencing of the dopamine D2 receptor (DRD2) in schizophrenics reveals three polymorphisms but no structural change in the receptor.
        Genomics. 1991; 11: 8-14
        • Seeman P
        • Van Tol HHM
        Dopamine receptor pharmacology.
        Trends Pharmacol Sci. 1994; 15: 264-270
        • Seeman P
        • Niznik HB
        • Guan H-C
        • Booth G
        • Ulpian C
        Link between D1 and D2 dopamine receptors is reduced in schizophrenia and Huntington diseased brain.
        in: Proc Natl Acad Sci USA. 86. 1989: 10156-10160
        • Seeman P
        • Ohara K
        • Ulpian C
        • et al.
        Schizophrenia: Normal sequence in the dopamine D2 receptor region that couples to G-proteins.
        Neuropsychopharmacology. 1993; 8: 137-142
        • Shaikh S
        • Collier D
        • Kerwin RW
        • et al.
        Dopamine D4 receptor subtypes and response to clozapine.
        Lancet. 1994; 341: 116
        • Shaikh S
        • Collier D
        • Arranz M
        • Ball D
        • Gill M
        • Kerwin R
        DRD2 Ser311/Cys311 polymorphism in schizophrenia.
        Lancet. 1994; 343: 1045-1046
        • Sobell J
        • Sigurdson DC
        • Heston L
        • Sommer S
        S311C D2DR variant: No association with schizophrenia.
        Lancet. 1994; 344: 621-622
        • Su Y
        • Burke J
        • O'Neill A
        • et al.
        Exclusion of linkage between schizophrenia and the D2 receptor gene region of chromosome 11q in 112 Irish multiplex families.
        Arch Gen Psychiatry. 1993; 50: 205-211
        • Sunahara RK
        • Guan H-C
        • O'Dowd BF
        • et al.
        Cloning of the gene for a human dopamine D5 receptor with higher affinity for dopamine than D1.
        Nature. 1991; 350: 614-619
        • Toru M
        Seishinbunretsubyo no yakuri.
        Chu-Gai Igakusha Co, Toronto1984
        • Van Tol HHM
        • Bunzow JR
        • Guan H-C
        • et al.
        Cloning of the gene for a human dopamine D4 receptor with high affinity for the antipsychotic clozapine.
        Nature. 1991; 350: 610-614
        • Van Tol HHM
        • Wu CM
        • Guan H-C
        • et al.
        Multiple dopamine D4 receptor variants in the human population.
        Nature. 1992; 358: 149-152
        • Wang ZW
        • Black D
        • Andreasen NC
        • Crowe RR
        A linkage study of chromosome 11q in schizophrenia.
        Arch Gen Psychiatry. 1993; 50: 212-216
        • Yang L
        • Li T
        • Wiese C
        • et al.
        No association between schizophrenia and homozygosity at the D3 dopamine receptor gene.
        Am J Med Genet. 1993; 48: 83-86

      Article info

      Publication history

      Received in revised form: September 29, 1995
      Received: June 13, 1995

      Footnotes

      This study was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture and Science, Japan (06770777 and 07770777), the Pharmachopsychiatry Research Foundation, Japan, and the Japan Foundation for Neuroscience and Mental Health. Drs. Zhang and Lin are recipients of a scholarship from the Mental Health Okamoto Memorial Foundation, Japan.

      This work was presented at the World Regional Congress on Biological Psychiatry at Sao Paulo, Brazil, on May 7–10, 1995, and was the winner of the WFSBP poster award.

      Identification

      DOI: https://doi.org/10.1016/0006-3223(95)00673-7

      Copyright

      © 1996 Society of Biological Psychiatry. Published by Elsevier Inc.

      ScienceDirect

      Access this article on ScienceDirect

      The content on this site is intended for healthcare professionals.


      We use cookies to help provide and enhance our service and tailor content. To update your cookie settings, please visit the Cookie Preference Center for this site.
      Copyright © 2023 Elsevier Inc. except certain content provided by third parties.


      RELX