Krebs M O, Sautel F, Bourdel M C, Sokoloff P, Schwartz J C, Olié J P, Lôo H, Poirier M F
Service Hospitalo-Universitaire de Santé Mentale et Thérapeutique, Hôpital Sainte-Anne, Université René Descartes, Paris V, France.
Mol Psychiatry. 1998 Jul;3(4):337-41. doi: 10.1038/sj.mp.4000411.
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.
在一项针对法国白种人群中多巴胺D3受体（DRD3）基因的Bal I多态性的关联研究中，对符合精神分裂症诊断标准（n = 89，DSM-III-R标准）的患者和对照组（n = 52）进行的总体比较未发现显著差异。然而，与无药物滥用史的患者（P = 0.010）或对照组（P = 0.047）相比，有终生药物滥用合并症的精神分裂症患者（n = 36）中纯合子的频率显著更高；与治疗难治性患者（n = 19；P = 0.037）相比，在抗精神病药物反应者患者中纯合子频率也显著更高。治疗反应和终生药物滥用的综合特征与纯合子密切相关。我们提出，DRD3基因Bal I多态性的纯合子与药物滥用易感性和/或精神分裂症的药物敏感特征相关，而非与精神分裂症本身相关，这一假设与该多态性与阿片类药物依赖的正相关（见Duaux等人的配套文章）以及DRD3在药物依赖机制和抗精神病药物的抗精神病作用中的参与是一致的。
