Dopamine D4 receptor 48-bp repeat polymorphism: no association with response to antipsychotic treatment, but association with catatonic schizophrenia

The dopamine D-4 receptor (DRD4) may play a role in the pathogenesis of neu ropsychiatric disease and in the action of dopaminergic drugs. The 48-bp re peat polymorphism (48-bp VNTR) coding for a 16-amino acid segment in the th ird cytoplasmatic loop of the DRD4 was studied as a predictor of the therap eutic response to antipsychotics and as susceptibility factor for schizophr enia. We included 638 in-patients with acute schizophrenic, schizoaffective (mainly schizophrenic), and other nonaffective psychoses, as well as two r eference groups: one with 278 in-patients with non-psychiatric diseases, an d one with 474 healthy volunteers, Catatonic patients (DSM-IV 295.2) more f requently carried the DRD4 D-4.2 and D-4.3 allele than did all other schizo phrenic 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 43-bp VNTR was not a predictor for therape utic outcome measured by the positive and negative symptoms scale, A total of 1390 subjects showed between 1 and 10 repeats (D-4.1 and D-4.10), with 2 5 different genotypes. These data exclude a major role of DRD4 48-bp VNTR i n response to antipsychotic therapy and as susceptibility factor for schizo phrenia, but catatonic schizophrenia may be associated with the D-4.2 and D -4.3 alleles.