Frodl Thomas, Szyf Moshe, Carballedo Angela, Ly Victoria, Dymov Sergiy, Vaisheva Farida, Morris Derek, Fahey Ciara, Meaney James, Gill Michael, Booij Linda
Department of Psychiatry, University of Dublin, Trinity College Dublin, Ireland (Frodl, Carballedo, Morris, Gill); Institute of Neuroscience, University of Dublin, Trinity College Dublin, Ireland (Frodl, Gill); Department of Psychiatry and Psychotherapy, University of Regensburg, Germany (Frodl); Centre of Advanced Medical Imaging, St. James's Hospital & Trinity College Dublin, Ireland (Frodl, Meaney); Department of Pharmacology and Therapeutics, McGill University, Montréal, Canada (Szyf, Ly, Dymov, Vaisheva); Neuropsychiatric Genetics Research Group, Department of Psychiatry and Institute of Molecular Medicine, University of Dublin, Trinity College Dublin, Ireland ( Fahey, Gill); Department of Psychology and Psychiatry, Queen's University, Kingston, Canada (Booij); Sainte-Justine Hospital Research Center and Université de Montréal, Montréal, Canada (Booij); Department of Psychiatry, McGill University, Montréal, Canada (Booij).
J Psychiatry Neurosci. 2015 Sep;40(5):296-305. doi: 10.1503/jpn.140180.
The aim of the present study was to investigate the association of fMRI blood oxygen-level dependent (BOLD) reactivity with the level of epigenetic methylation of SLC6A4 in blood DNA from a sample of healthy participants and patients with major depressive disorder (MDD).
We investigated patients with MDD and healthy controls using fMRI and an emotional attention-shifting task. We assessed site-specific DNA methylation of a previously characterized SLC6A4 region in peripheral blood DNA using pyrosequencing.
Our study involved 25 patients with MDD and 35 healthy controls. Activation in the anterior insula elicited by negative emotional content was significantly positively associated with the degree of SLC6A4 methylation. Significantly negative associations were observed between activation in the posterior insula and the degree of SLC6A4 methylation when judging the geometry of pictures after seeing negative in contrast to positive emotional stimuli. Healthy controls with a high degree of SLC6A4 methylation depicted significantly more activity elicited by positive stimuli in limbic regions and more activity elicited by negative stimuli in limbic as well as cognitive control regions than those with a low degree of SLC6A4 methylation.
It is impossible to measure methylation directly in the brain and thus we assessed peripheral methylation of SLC6A4. Since the association was cross-sectional, no conclusion about cause and effect can be drawn.
Our study provides further support to the hypothesis that particular DNA methylation states that are associated with brain function during emotion processing are detectable in the periphery.
本研究旨在调查功能磁共振成像（fMRI）血氧水平依赖（BOLD）反应性与健康参与者和重度抑郁症（MDD）患者血液DNA中SLC6A4基因表观遗传甲基化水平之间的关联。
我们使用fMRI和情绪注意力转移任务对MDD患者和健康对照者进行了研究。我们采用焦磷酸测序法评估外周血DNA中一个先前已鉴定的SLC6A4区域的位点特异性DNA甲基化情况。
我们的研究纳入了25例MDD患者和35名健康对照者。负面情绪内容引发的前脑岛激活与SLC6A4甲基化程度显著正相关。与正面情绪刺激相比，在看到负面情绪刺激后判断图片几何形状时，后脑岛激活与SLC6A4甲基化程度之间观察到显著负相关。与SLC6A4甲基化程度低的健康对照者相比，SLC6A4甲基化程度高的健康对照者在边缘区域对正面刺激引发的活动明显更多，在边缘区域以及认知控制区域对负面刺激引发的活动也更多。
无法直接测量大脑中的甲基化情况，因此我们评估了SLC6A4的外周甲基化。由于该关联是横断面研究，无法得出因果关系的结论。
我们的研究进一步支持了这样的假设，即在情绪处理过程中与脑功能相关的特定DNA甲基化状态在外周是可检测到的。
