Institute of Psychiatry, University of Bologna, Bologna, Italy.
J Affect Disord. 2012 Dec 15;142(1-3):82-9. doi: 10.1016/j.jad.2012.03.047. Epub 2012 Aug 4.
Depression is considered to be the result of a complicated synergy between genetic and environmental factors. Several genes of the serotonergic neurotransmission have been related to depression phenotypes, however results are inconsistent, possibly due to the oversight of the role of environmental stress.
We examined gene-environment (GxE) interactions with serotonergic genes on depressive symptoms and neuroticism in a homogeneous population-based sample of 415 females. We chose several genetic variants within candidate genes (SLC6A4, TPH2, HTR1A) that have been previously found to provide some evidence of association with depression outcomes.
Single marker analyses showed a significant GxE interaction with several TPH2 variants, including rs4570625, on depressive symptoms. Significant GxE interactions were also observed with TPH2 haplotypes. No reliable associations were observed with SLC6A4 and HTR1A genes. We did not find any robust evidence of a direct impact of serotonergic genes on depressive symptoms or neuroticism.
Due to the high number of analyses conducted, results must be interpreted with caution.
The present study indicates an association between TPH2 and depressive symptoms that is conditional on prior experience of stressful life events. Further evidence is provided about the role of the environment in genetic vulnerability to depression.
抑郁症被认为是遗传和环境因素复杂协同作用的结果。几种 5-羟色胺能神经递质的基因与抑郁表型有关，但结果不一致，可能是由于忽视了环境应激的作用。
我们在一个同质的基于人群的 415 名女性样本中研究了 5-羟色胺能基因与抑郁症状和神经质的基因-环境（GxE）相互作用。我们选择了候选基因（SLC6A4、TPH2、HTR1A）内的几个遗传变异体，这些变异体先前发现与抑郁结果有一定的关联证据。
单标记分析显示，与 TPH2 基因的几个变体（包括 rs4570625）存在显著的 GxE 相互作用，与 TPH2 单倍型也存在显著的 GxE 相互作用。SLC6A4 和 HTR1A 基因与抑郁症状无明显关联。我们没有发现 5-羟色胺能基因对抑郁症状或神经质有直接影响的可靠证据。
由于进行了大量的分析，结果必须谨慎解释。
本研究表明 TPH2 与抑郁症状之间存在关联，这种关联取决于先前经历的应激性生活事件。进一步证明了环境在遗传易感性与抑郁之间的作用。
