Serretti A, Cusin C, Lattuada E, Lilli R, Lorenzi C, Di Bella D, Catalano M, Smeraldi E
Department of Neuropsychiatric Sciences, Istituto Scientifico H San Raffaele, University of Milan School of Medicine, Italy.
Am J Med Genet. 1999 Oct 15;88(5):481-5.
Previously, we reported an association of the dopamine receptor D4 (DRD4) gene with delusional symptomatology of major psychoses. However, DRD4 variants accounted for only 2% of the phenotypic variance, indicating that contributions from other genes were probable. The serotonin transporter gene is a primary candidate in major psychoses, and a functional polymorphism in the upstream regulatory region of the serotonin transporter gene (5-HTTLPR) has recently been reported to be associated with a number of psychopathological conditions. In the present study we investigated the original cohort of subjects to evaluate the 5-HTTLPR possible influence on the psychopathology of major psychoses in interaction with DRD4. Four hundred and sixty-one inpatients affected by major psychoses were assessed by the Operational Criteria Checklist for Psychotic Illness (OPCRIT) and were also typed for the 5-HTTLPR and DRD4 variants using polymerase chain reaction techniques. Mania, depression, delusion, and disorganization were the four symptomatologic factors used as phenotype definition. 5-HTTLPR variants did not significantly influence the previously reported association of DRD4 with delusional symptoms. No interaction was observed on the other symptom factors. The serotonin transporter gene does not, therefore, interact with DRD4 in determining the symptomatology of major psychoses.
此前，我们报道了多巴胺受体D4（DRD4）基因与主要精神病性障碍的妄想症状之间存在关联。然而，DRD4基因变异仅占表型变异的2%，这表明其他基因可能也有作用。血清素转运体基因是主要精神病性障碍的一个主要候选基因，最近有报道称血清素转运体基因（5-HTTLPR）上游调控区域的一个功能性多态性与多种精神病理状况有关。在本研究中，我们对最初的受试者队列进行了调查，以评估5-HTTLPR与DRD4相互作用时对主要精神病性障碍精神病理学的可能影响。采用精神病性疾病操作标准检查表（OPCRIT）对461名患有主要精神病性障碍的住院患者进行评估，并使用聚合酶链反应技术对5-HTTLPR和DRD4基因变异进行分型。躁狂、抑郁、妄想和紊乱是用作表型定义的四个症状学因素。5-HTTLPR基因变异并未显著影响先前报道的DRD4与妄想症状之间的关联。在其他症状因素上未观察到相互作用。因此，在决定主要精神病性障碍的症状学时，血清素转运体基因与DRD4不存在相互作用。
