Dopamine D3 receptor gene variants and substance abuse in schizophrenia.
In an association study of the Bal I polymorphism in the dopamine D3 receptor (DRD3) gene in a French Caucasian population, global comparison of patients with schizophrenia (n = 89, DSM-III-R criteria) and controls (n = 52) led to non-significant differences. However, the homozygosity was significantly more frequent in schizophrenic patients with lifetime substance abuse comorbidity (n = 36) as compared to patients with no history of substance abuse (P = 0.010) or to controls (P = 0.047) and in neuroleptic responder patients as compared to treatment-refractory patients (n = 19; P = 0.037). The combined characteristics treatment response and lifetime substance abuse were strongly associated with homozygosity. We propose that homozygosity for the Bal I polymorphism DRD3 gene is associated with predisposition to substance abuse and/or the pharmacosensitive characteristic of schizophrenia rather than with schizophrenia itself, an hypothesis in agreement with the positive association of this polymorphism with opiate dependence (see companion article by Duaux et al) and the involvement of DRD3 in both pharmacodependence mechanisms and antipsychotic effects of neuroleptics.
Krebs
M O
MO
Service Hospitalo-Universitaire de Santé Mentale et Thérapeutique, Hôpital Sainte-Anne, Université René Descartes, Paris V, France. SHU@CHSA.broca.inserm.fr
Sautel
F
F
Bourdel
M C
MC
Sokoloff
P
P
Schwartz
J C
JC
Olié
J P
JP
Lôo
H
H
Poirier
M F
MF
D015897:Comorbidity; D015252:Deoxyribonucleases, Type II Site-Specific; D005260:Female; D005602:France; D014644:Genetic Variation; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008297:Male; D012150:Polymorphism, Restriction Fragment Length; D011618:Psychotic Disorders / Q000188:drug therapy / Q000235:genetics*; D011619:Psychotropic Drugs / Q000627:therapeutic use; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D050637:Receptors, Dopamine D3; D012016:Reference Values; D012559:Schizophrenia / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D019966:Substance-Related Disorders / Q000150:complications / Q000235:genetics*; D044465:White People
C493593:DRD3 protein, human; D011619:Psychotropic Drugs; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D015252:Deoxyribonucleases, Type II Site-Specific; C060616:TGGCCA-specific type II deoxyribonucleases