van der Knaap Lisette J, Riese Harriëtte, Hudziak James J, Verbiest Michael M P J, Verhulst Frank C, Oldehinkel Albertine J, van Oort Floor V A
From the Department of Child and Adolescent Psychiatry/Psychology (van der Knaap, Hudziak, Verhulst, van Oort), Erasmus Medical Center, Sophia Children's Hospital, Rotterdam, the Netherlands; Interdisciplinary Center Psychopathology and Emotion Regulation (ICPE) (Riese, Oldehinkel), Department of Psychiatry, University of Groningen, University Medical Center Groningen, the Netherlands; Vermont Center for Children, Youth, and Families (Hudziak), The University of Vermont, Burlington, Vermont; and Department of Internal Medicine (Verbiest), Erasmus Medical Center, Rotterdam, the Netherlands.
Psychosom Med. 2015 Apr;77(3):246-55. doi: 10.1097/PSY.0000000000000159.
Adverse life events increase vulnerability to affective disorders later in life, possibly mediated by methylation of the serotonin transporter gene (SLC6A4). We investigated the relationship of SLC6A4 methylation with various types of adversity (perinatal adversity, traumatic youth experiences and stressful life events [SLEs]), as well as with the timing of SLEs (during childhood [0-11 years] or during adolescence [12-15 years]). In addition, we investigated whether different serotonin-transporter-linked polymorphic region genotypes were equally sensitive to SLE-related methylation.
In a population sample of 939 adolescents (mean age = 16.2 years), we assessed SLC6A4 methylation, SLC6A4 functionality (serotonin-transporter-linked polymorphic region "long" and "short" alleles, and rs25531), and adverse life events.
Only a higher number of SLEs was positively associated with higher SLC6A4 methylation (B = 0.11, p = .011). Adolescent SLEs were associated with higher SLC6A4 methylation (B = 0.13, p = .004) independently of childhood SLEs (B = 0.02, p = .57). L-allele homozygotes showed a greater impact of SLEs on methylation (B = 0.37, p < .001) than did s-allele carriers (B = 0.04, p = .66), resulting in higher levels of SLC6A4 methylation for l-allele homozygotes among those experiencing high levels of SLEs.
Our findings demonstrate a higher level of SLC6A4 methylation after SLEs in adolescents, with a more pronounced association for SLEs during adolescence than during childhood. Considering the allele-specific sensitivity of SLC6A4 methylation to SLEs, this study may help clarify the role of SLC6A4 in the development of affective disorders.
不良生活事件会增加日后患情感障碍的易感性，这可能由血清素转运体基因（SLC6A4）的甲基化介导。我们研究了SLC6A4甲基化与各种类型的逆境（围产期逆境、创伤性青少年经历和应激性生活事件[SLEs]）之间的关系，以及与SLEs发生时间（童年期[0 - 11岁]或青春期[12 - 15岁]）的关系。此外，我们还研究了不同的血清素转运体连锁多态性区域基因型对SLEs相关甲基化是否同样敏感。
在一个由939名青少年组成的人群样本（平均年龄 = 16.2岁）中，我们评估了SLC6A4甲基化、SLC6A4功能（血清素转运体连锁多态性区域“长”和“短”等位基因，以及rs25531）和不良生活事件。
只有更多的SLEs与更高的SLC6A4甲基化呈正相关（B = 0.11，p = 0.011）。青少年SLEs与更高的SLC6A4甲基化相关（B = 0.13，p = 0.004），独立于童年期SLEs（B = 0.02，p = 0.57）。与s等位基因携带者（B = 0.04，p = 0.66）相比，L等位基因纯合子显示SLEs对甲基化的影响更大（B = 0.37，p < 0.001），导致在经历高水平SLEs的人群中，L等位基因纯合子的SLC6A4甲基化水平更高。
我们的研究结果表明，青少年经历SLEs后SLC6A4甲基化水平更高，与童年期相比，青春期的SLEs关联更为明显。考虑到SLC6A4甲基化对SLEs的等位基因特异性敏感性，本研究可能有助于阐明SLC6A4在情感障碍发展中的作用。
