Department of Biomedical and NeuroMotor Sciences, University of Bologna, Italy.
Eur Neuropsychopharmacol. 2013 Oct;23(10):1125-42. doi: 10.1016/j.euroneuro.2013.03.013. Epub 2013 Jun 3.
Suicide is one of the leading causes of death in the world. Its aetiology is complex and diverse, however, epidemiological studies show that suicidal behavior is partly heritable. Neurobiological evidence implicates serotonergic dysfunction in suicidality, stimulating genetic research to focus on genes related to the serotonergic system. In this paper, we review evidence from studies examining the association between various serotonergic genes (Tryptophan Hydroxylase genes: TPH1; TPH2, Serotonin Transporter gene: 5-HTTLPR in SLC6A4, Serotonin Receptor genes: HTR1A, HTR2A, HTR1B, HTR2C and Monoamine Oxidase A gene: MAOA) and suicidal behavior. The data show associations between variation on the TPH1 gene and 5-HTTLPR gene and violent suicidal behavior in Caucasian populations, with the least inconsistencies. Results are mixed for the TPH2 gene and serotonin receptor genes, but for some genes, studies that include haplotypic analyses or that examine a larger coding region of the genes tend to provide more reliable results. Findings on endophenotypes of suicidality, such as aggression and impulsivity traits, show positive associations for the TPH1, HTR2A, and MAOA genes, but need further replication, since negative associations are also occasionally reported. Since genes can only partially explain suicidal risk, several studies during the past decade have tried to incorporate environmental factors in the susceptibility model. Studies to date show that variation on the 5-HTTLPR, MAOA and HTR2A gene can interact with stressful life events to increase risk for suicidal behavior. Limitations of case-control studies are discussed and future considerations are put forward with regard to endophenotypic measurements and gene-environment interactions.
自杀是世界上主要的死亡原因之一。其病因复杂多样，然而，流行病学研究表明，自杀行为部分是遗传的。神经生物学证据表明，5-羟色胺能功能障碍与自杀行为有关，这刺激了遗传研究集中于与 5-羟色胺能系统相关的基因。在本文中，我们回顾了研究自杀行为与各种 5-羟色胺能基因（色氨酸羟化酶基因：TPH1；TPH2、5-羟色胺转运体基因：SLC6A4 中的 5-HTTLPR、5-羟色胺受体基因：HTR1A、HTR2A、HTR1B、HTR2C 和单胺氧化酶 A 基因：MAOA）之间关联的研究证据。数据表明，TPH1 基因和 5-HTTLPR 基因的变异与白种人群的暴力性自杀行为有关，一致性最高。TPH2 基因和 5-羟色胺受体基因的结果则较为复杂，但对于一些基因，进行单体型分析或检查基因更大的编码区的研究往往能提供更可靠的结果。对于自杀行为的内表型，如攻击性和冲动性特征的研究表明，TPH1、HTR2A 和 MAOA 基因呈正相关，但需要进一步复制，因为也偶尔有阴性关联的报道。由于基因只能部分解释自杀风险，过去十年中的几项研究试图将环境因素纳入易感性模型中。迄今为止的研究表明，5-HTTLPR、MAOA 和 HTR2A 基因的变异与生活应激事件相互作用会增加自杀行为的风险。讨论了病例对照研究的局限性，并就内表型测量和基因-环境相互作用提出了未来的考虑。
