Institute of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, Budapest, Hungary.
Behav Brain Funct. 2010 Jan 12;6:4. doi: 10.1186/1744-9081-6-4.
In the development of borderline personality disorder (BPD) both genetic and environmental factors have important roles. The characteristic affective disturbance and impulsive aggression are linked to imbalances in the central serotonin system, and most of the genetic association studies focused on serotonergic candidate genes. However, the efficacy of dopamine D2 receptor (DRD2) blocking antipsychotic drugs in BPD treatment also suggests involvement of the dopamine system in the neurobiology of BPD.
In the present study we tested the dopamine dysfunction hypothesis of impulsive self- and other-damaging behaviors: borderline and antisocial traits were assessed by Structured Clinical Interview for Diagnosis (SCID) for DSM-IV in a community-based US sample of 99 young adults from low-to-moderate income families. For the BPD trait analyses a second, independent group was used consisting of 136 Hungarian patients with bipolar or major depressive disorder filling out self-report SCID-II Screen questionnaire. In the genetic association analyses the previously indicated polymorphisms of the catechol-O-methyl-transferase (COMT Val158Met) and dopamine transporter (DAT1 40 bp VNTR) were studied. In addition, candidate polymorphisms of the DRD2 and DRD4 dopamine receptor genes were selected from the impulsive behavior literature.
The DRD2 TaqI B1-allele and A1-allele were associated with borderline traits in the young adult sample (p = 0.001, and p = 0.005, respectively). Also, the DRD4 -616 CC genotype appeared as a risk factor (p = 0.02). With severity of abuse accounted for in the model, genetic effects of the DRD2 and DRD4 polymorphisms were still significant (DRD2 TaqIB: p = 0.001, DRD2 TaqIA: p = 0.008, DRD4 -616 C/G: p = 0.002). Only the DRD4 promoter finding was replicated in the independent sample of psychiatric inpatients (p = 0.007). No association was found with the COMT and DAT1 polymorphisms.
Our results of the two independent samples suggest a possible involvement of the DRD4 -616 C/G promoter variant in the development of BPD traits. In addition, an association of the DRD2 genetic polymorphisms with impulsive self-damaging behaviors was also demonstrated.
在边缘型人格障碍（BPD）的发展中，遗传和环境因素都起着重要作用。特征性的情感障碍和冲动性攻击与中枢 5-羟色胺系统的失衡有关，大多数遗传关联研究都集中在 5-羟色胺能候选基因上。然而，多巴胺 D2 受体（DRD2）阻断抗精神病药物在 BPD 治疗中的疗效也表明多巴胺系统参与了 BPD 的神经生物学。
本研究通过结构临床访谈（SCID）对诊断（DSM-IV），在一个基于社区的美国样本中评估了冲动的自我和他人伤害行为的多巴胺功能障碍假说：99 名来自中低收入家庭的年轻成年人。对于 BPD 特征分析，我们使用了另一个独立的小组，由 136 名来自匈牙利的双相或重性抑郁障碍患者组成，他们填写了自我报告的 SCID-II 筛查问卷。在遗传关联分析中，我们研究了先前指出的儿茶酚-O-甲基转移酶（COMT Val158Met）和多巴胺转运体（DAT1 40 bp VNTR）的多态性。此外，从冲动行为文献中选择了 DRD2 和 DRD4 多巴胺受体基因的候选多态性。
DRD2 TaqI B1-等位基因和 A1-等位基因与年轻成年人样本中的边缘特征相关（p = 0.001，和 p = 0.005，分别）。此外，DRD4-616 CC 基因型似乎是一个风险因素（p = 0.02）。在模型中考虑了滥用的严重程度，DRD2 和 DRD4 多态性的遗传效应仍然显著（DRD2 TaqIB：p = 0.001，DRD2 TaqIA：p = 0.008，DRD4-616 C/G：p = 0.002）。只有 DRD4 启动子的发现可以在独立的精神科住院患者样本中复制（p = 0.007）。与 COMT 和 DAT1 多态性没有关联。
我们在两个独立样本中的结果表明，DRD4-616 C/G 启动子变异可能参与了 BPD 特征的发展。此外，还证明了 DRD2 遗传多态性与冲动性自我伤害行为有关。
