Anxiety and depression in children and adults: influence of serotonergic and neurotrophic genes?
Anxiety and depression in children and adults: influence of serotonergic and neurotrophic genes?
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DOI：
10.1111/j.1601-183x.2010.00619.x
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发表时间：
2010-10
期刊：
影响因子：
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通讯作者：
Boomsma DI
中科院分区：
文献类型：
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作者：
Middeldorp CM;Slof-Op 't Landt MC;Medland SE;van Beijsterveldt CE;Bartels M;Willemsen G;Hottenga JJ;de Geus EJ;Suchiman HE;Dolan CV;Neale MC;Slagboom PE;Boomsma DI
关于焦虑和抑郁的病因有两个主要假说：单胺假说和异常应激反应部分通过神经发生减少而起作用的假说。关联研究的重点是参与这些过程的基因，但结果尚无定论。本研究调查了 45 个单核苷酸多态性 (SNP) 对编码血清素受体 1A、1D、2A、儿茶酚 O-甲基转移酶 (COMT)、色氨酸羟化酶 2 型 (TPH2)、脑源性神经营养因子 (BDNF)、PlexinA2 和 G 蛋白偶联信号传导 (RGS) 2、4、16 调节因子的基因的影响。 11 年间，对超过 11,000 名成年人（对 1504 名受试者进行了基因分型）以及在 7、10、12 岁和青春期对 20,000 多名双胞胎（对 1078 名受试者进行了基因分型）的焦虑抑郁 (A/D) 症状进行了五次评估。在这两个队列中，分析了一个纵向模型，该模型随着时间的推移在所有 A/D 测量上加载了一个潜在因素。在该潜在因素水平上建模的遗传关联效应在儿童和成人中分别具有 60% 和 70% 的可遗传性，并解释了大约 50% 的总表型方差。功效分析表明，样本包含 80% 的功效来检测解释 1.4% 到 3.6% 方差的效应。然而，没有 SNP 显示出对 A/D 的一致影响。总之，这项针对儿童和成人的纵向研究发现，血清素能系统或神经发生的核心调节因子中的 SNP 与 A/D 没有关联。总体而言，到目前为止，还没有令人信服的证据表明这些途径中的遗传变异在焦虑和抑郁的发展中发挥作用。
There are two major hypotheses regarding the etiology of anxiety and depression: the mono-amine hypothesis and the hypothesis of an abnormal stress response acting partly via reduced neurogenesis. Association studies have focused on genes involved in these processes, but with inconclusive results. This study investigated the effect of 45 single nucleotide polymorphisms (SNPs) in genes encoding for serotonin receptors 1A, 1D, 2A, catechol-O-methyltransferase (COMT), tryptophane hydroxylase type 2 (TPH2), brain derived neurotrophic factor (BDNF), PlexinA2 and regulators of G-protein-coupled signaling (RGS) 2, 4, 16. Anxious depression (A/D) symptoms were assessed five times in 11 years in over 11 000 adults with 1504 subjects genotyped and at age 7, 10, 12 and during adolescence in over 20 000 twins with 1078 subjects genotyped. In both cohorts, a longitudinal model with one latent factor loading on all A/D measures over time was analysed. The genetic association effect modeled at the level of this latent factor was 60% and 70% heritable in the children and adults, respectively, and explained around 50% of the total phenotypic variance. Power analyses showed that the samples contained 80% power to detect an effect explaining between 1.4% and 3.6% of the variance. However, no SNP showed a consistent effect on A/D. To conclude, this longitudinal study in children and adults found no association of SNPs in the serotonergic system or core regulators of neurogenesis with A/D. Overall, there has been no convincing evidence, so far, for a role of genetic variation in these pathways in the development of anxiety and depression.