Department of Psychiatry and Neurosciences, Applied Life Sciences Institute of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, Hiroshima, Japan.
Department of Psychiatry and Neurosciences, Applied Life Sciences Institute of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, Hiroshima, Japan; Department of Neuropsychiatry, Kochi Medical School, Kochi University, Kohasu, Oko-cho, Nankoku, Kochi, Japan.
J Psychiatr Res. 2014 Jun;53:47-53. doi: 10.1016/j.jpsychires.2014.02.002. Epub 2014 Feb 21.
We examined the utility of DNA methylation profiles at the CpG island of SLC6A4 (DMS) as a diagnostic biomarker for major depression (MD). In addition, the relationship between DMS and the serotonin transporter gene-linked polymorphic region (5-HTTLPR) allele, the severity of symptoms, number of early adversities, and therapeutic responses to antidepressants were examined. Genomic DNA was extracted from peripheral blood of Japanese healthy controls and patients with MD before and after treatment. DMS was analyzed using a MassARRAY Compact System. The severity of depression was evaluated using the Hamilton Rating Scale for Depression, and early adversity was evaluated using the Early Trauma Inventory. We were unable to distinguish between and healthy controls, or between unmedicated patients and medicated patients using DMS. The 5-HTTLPR allele had no significant effect on DMS. The methylation rates for several CpGs differed significantly after treatment. Notably, the methylation rate of CpG 3 in patients with better therapeutic responses was significantly higher than that in patients with poorer responses. Although further studies examining the function of specific CpG units of SLC6A4 are required, these results suggest that the pre-treatment methylation rate of SLC6A4 is associated with therapeutic responses to antidepressants in unmedicated patients with MD.
我们研究了 SLC6A4（DMS）CpG 岛的 DNA 甲基化谱作为重度抑郁症（MD）诊断生物标志物的效用。此外，还研究了 DMS 与 5-羟色胺转运体基因相关多态性区域（5-HTTLPR）等位基因、症状严重程度、早期逆境数量以及抗抑郁药治疗反应之间的关系。从日本健康对照者和 MD 患者治疗前后的外周血中提取基因组 DNA。使用 MassARRAY Compact 系统分析 DMS。使用汉密尔顿抑郁评定量表评估抑郁严重程度，使用早期创伤量表评估早期逆境。我们无法使用 DMS 区分健康对照者和 MD 患者，也无法区分未用药患者和用药患者。5-HTTLPR 等位基因对 DMS 没有显著影响。治疗后几个 CpG 的甲基化率有显著差异。值得注意的是，治疗反应较好的患者中 CpG3 的甲基化率明显高于治疗反应较差的患者。虽然需要进一步研究 SLC6A4 特定 CpG 单位的功能，但这些结果表明，未经治疗的 MD 患者中，SLC6A4 的治疗前甲基化率与抗抑郁药治疗反应相关。
