Kaut Oliver, Sharma Amit, Schmitt Ina, Hurlemann René, Wüllner Ullrich
Department of Neurology, University Clinic Bonn, Bonn, Germany.
Division of Medical Psychology, University of Bonn Medical Center, 53105 Bonn, Germany.
J Clin Neurosci. 2017 Sep;43:261-263. doi: 10.1016/j.jocn.2017.05.030. Epub 2017 Jun 20.
Epigenetic alterations provide a potential mechanism to account for the numerous gene-environment interactions that have been reported in association with neuropsychiatric phenotypes. In context to major depression disorder (MDD), where postmortem and neuroimaging studies provide insights into dysfunctional brain regions, involvement of genetic heterogeneity also revealed the complexity of this disorder. Despite intensive research during the past several decades and information from genome wide studies, pathophysiology of depressive disorders remained elusive. To evaluate the impact of epigenetic pressure on this disease, we took advantage of DNA isolated from different sections of human brain (prefrontal cortex and hippocampus) from clinically well defined depressed patients and healthy individuals and performed pyrosequencing for DNA methylation analysis. Herein, we focused on two genes DLG4 (PSD-95) and GJA-1 (Connexin43) known to be associated with neuropsychiatric behavior. Comparing MDD with controls we found no differences of DNA methylation. Our results clearly demonstrate that DNA methylation levels on these particular genes are not associated with depression related phenotype.
表观遗传改变提供了一种潜在机制，用以解释与神经精神表型相关的众多基因-环境相互作用。就重度抑郁症（MDD）而言，尸检和神经影像学研究揭示了功能失调的脑区，遗传异质性的参与也凸显了该疾病的复杂性。尽管在过去几十年中进行了深入研究并获得了全基因组研究的信息，但抑郁症的病理生理学仍然难以捉摸。为了评估表观遗传压力对这种疾病的影响，我们利用从临床明确诊断的抑郁症患者和健康个体的人脑不同部位（前额叶皮质和海马体）分离的DNA，进行焦磷酸测序以分析DNA甲基化。在此，我们聚焦于已知与神经精神行为相关的两个基因DLG4（PSD-95）和GJA-1（连接蛋白43）。将MDD患者与对照组进行比较，我们发现DNA甲基化没有差异。我们的结果清楚地表明，这些特定基因上的DNA甲基化水平与抑郁症相关表型无关。
