Kahl Kai G, Georgi Karsten, Bleich Stefan, Muschler Marc, Hillemacher Thomas, Hilfiker-Kleinert Denise, Schweiger Ulrich, Ding Xiaoqi, Kotsiari Alexandra, Frieling Helge
Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
J Psychiatr Res. 2016 May;76:66-73. doi: 10.1016/j.jpsychires.2016.02.002. Epub 2016 Feb 10.
Alterations in brain glucose metabolism and in peripheral glucose metabolism have frequently been observed in major depressive disorder (MDD). The insulin independent glucose transporter 1 (GLUT1) plays a key role in brain metabolism while the insulin-dependent GLUT4 is the major glucose transporter for skeletal and cardiac muscle. We therefore examined methylation of GLUT1 and GLUT4 in fifty-two depressed inpatients and compared data to eighteen healthy comparison subjects. DNA methylation of the core promoter regions of GLUT1 and GLUT4 was assessed by bisulfite sequencing. Further factors determined were fasting glucose, cortisol, insulin, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). We found significantly increased methylation of the GLUT1 in depressed inpatients compared to healthy comparison subjects (CG). Further findings comprise increased concentrations of fasting cortisol, glucose, insulin, and increased IL-6 and TNF-α. After six weeks of inpatient treatment, significantly lower GLUT1 methylation was observed in remitted patients compared to non-remitters. GLUT4 methylation was not different between depressed patients and CG, and did not differ between remitted and non-remitted patients. Although preliminary we conclude from our results that the acute phase of major depressive disorder is associated with increased GLUT1 methylation and mild insulin resistance. The successful treatment of depression is associated with normalization of GLUT1 methylation in remitters, indicating that this condition may be reversible. Failure of normalization of GLUT1 methylation in non-remitters may point to a possible role of impeded brain glucose metabolism in the maintenance of MDD.
在重度抑郁症（MDD）中，经常观察到大脑葡萄糖代谢和外周葡萄糖代谢的改变。胰岛素非依赖性葡萄糖转运蛋白1（GLUT1）在大脑代谢中起关键作用，而胰岛素依赖性GLUT4是骨骼肌和心肌的主要葡萄糖转运蛋白。因此，我们检测了52名抑郁症住院患者中GLUT1和GLUT4的甲基化情况，并将数据与18名健康对照者进行比较。通过亚硫酸氢盐测序评估GLUT1和GLUT4核心启动子区域的DNA甲基化。还测定了空腹血糖、皮质醇、胰岛素、白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）等其他因素。我们发现，与健康对照者相比，抑郁症住院患者中GLUT1的甲基化显著增加（CG）。进一步的发现包括空腹皮质醇、葡萄糖、胰岛素浓度升高，以及IL-6和TNF-α升高。经过六周的住院治疗，与未缓解的患者相比，缓解患者的GLUT1甲基化显著降低。抑郁症患者与CG之间的GLUT4甲基化没有差异，缓解患者与未缓解患者之间也没有差异。尽管我们的研究结果是初步的，但我们得出结论，重度抑郁症的急性期与GLUT1甲基化增加和轻度胰岛素抵抗有关。抑郁症的成功治疗与缓解患者中GLUT1甲基化的正常化有关，表明这种情况可能是可逆的。未缓解患者中GLUT1甲基化未能正常化可能表明大脑葡萄糖代谢受阻在MDD维持中可能起作用。
