Dopamine D4 receptor 48-bp repeat polymorphism: no association with response to antipsychotic treatment, but association with catatonic schizophrenia.
The dopamine D4 receptor (DRD4) may play a role in the pathogenesis of neuropsychiatric disease and in the action of dopaminergic drugs. The 48-bp repeat polymorphism (48-bp VNTR) coding for a 16-amino acid segment in the third cytoplasmatic loop of the DRD4 was studied as a predictor of the therapeutic response to antipsychotics and as susceptibility factor for schizophrenia. We included 638 in-patients with acute schizophrenic, schizoaffective (mainly schizophrenic), and other nonaffective psychoses, as well as two reference groups: one with 278 in-patients with non-psychiatric diseases, and one with 474 healthy volunteers. Catatonic patients (DSM-IV 295.2) more frequently carried the DRD4 D4.2 and D4.3 allele than did all other schizophrenic cases (P < 0.001; OR: 2.7; CI: 1.5-4.9) and controls (P < 0.004; OR: 2.3; CI: 1.3-4.2). We found no significant difference in the DRD4 allele or in genotype frequencies in our comparison of all schizophrenic patients and controls. The subgroups with affected family members, and the subgroups with early or late onset of disease, also did not differ from the controls in DRD4 allele frequencies. The 48-bp VNTR was not a predictor for therapeutic outcome measured by the positive and negative symptoms scale. A total of 1390 subjects showed between 1 and 10 repeats (D4. 1 and D4.10), with 25 different genotypes. These data exclude a major role of DRD4 48-bp VNTR in response to antipsychotic therapy and as susceptibility factor for schizophrenia, but catatonic schizophrenia may be associated with the D4.2 and D4.3 alleles.
Kaiser
R
R
Institute of Clinical Pharmacology, Charité University Medical Centre, Humboldt University of Berlin, D-10098 Berlin, Germany.
Könneker
M
M
Henneken
M
M
Dettling
M
M
Müller-Oerlinghausen
B
B
Roots
I
I
Brockmöller
J
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D003024:Clozapine / Q000627:therapeutic use*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D050637:Receptors, Dopamine D3; D050638:Receptors, Dopamine D4; D012560:Schizophrenia, Catatonic / Q000188:drug therapy* / Q000235:genetics*
D014150:Antipsychotic Agents; C493593:DRD3 protein, human; C493599:DRD4 protein, human; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D050638:Receptors, Dopamine D4; D003024:Clozapine