Lazary Judit
Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary.
Neuropsychopharmacol Hung. 2010 Jun;12(2):347-54.
Although heritability of affective disorders is well accepted, several questions are still unsolved. The phenotype associated with the disorder is still uncertain, e.g., different disorders of the affective spectrum could be observed in the family of the patient. Furthermore, genetic studies failed to provide exact explanation for these questions either. We reported first that the role of the promoter region variant (5-HTTLPR) is not exclusive, and the middle region (tagged by the SNP rs140700) of the gene has also a significant role in the G x E model. Furthermore, we discovered a significant Gene x Gene x Environment interaction between 5-HTTLPR, rs140700 and threatening life events. Haplotype analyses of the serotonin transporter gene suggested that the majority of the S allele carriers for 5-HTTLPR with multiple threatening life events expressed high depression score, however, a subgroup with much lower depression score was also identified. In another study, interaction of 5-HTTLPR with the cannabinoid receptor 1 gene promoter was significantly associated with anxious phenotype. These results suggest that extremely high or low synaptic serotonin concentration could be associated with a high anxiety score. These findings call attention to the serotonergic dysfunction in the vulnerability for affective disorders.
尽管情感障碍的遗传力已被广泛接受，但仍有几个问题尚未解决。与该障碍相关的表型仍不明确，例如，在患者家族中可能观察到情感谱系的不同障碍。此外，遗传学研究也未能为这些问题提供确切解释。我们首次报道启动子区域变体（5-HTTLPR）的作用并非唯一，该基因的中间区域（由单核苷酸多态性rs140700标记）在基因-环境（G×E）模型中也具有重要作用。此外，我们发现5-HTTLPR、rs140700与威胁生命事件之间存在显著的基因-基因-环境相互作用。血清素转运体基因的单倍型分析表明，大多数携带5-HTTLPR的S等位基因且经历多次威胁生命事件的个体表现出高抑郁评分，但也鉴定出了一个抑郁评分低得多的亚组。在另一项研究中，5-HTTLPR与大麻素受体1基因启动子的相互作用与焦虑表型显著相关。这些结果表明，突触血清素浓度极高或极低可能与高焦虑评分相关。这些发现提醒人们注意情感障碍易感性中的血清素能功能障碍。
