Association between Glucocorticoid Receptor Methylation and Hippocampal Subfields in Major Depressive Disorder

被引:113
作者
Na, Kyoung-Sae [1 ]
Chang, Hun Soo [2 ]
Won, Eunsoo [3 ]
Han, Kyu-Man [3 ]
Choi, Sunyoung [4 ]
Tae, Woo Suk [5 ]
Yoon, Ho-Kyoung [3 ]
Kim, Yong-Ku [3 ]
Joe, Sook-Haeng [3 ]
Jung, In-Kwa [3 ]
Lee, Min-Soo [3 ]
Ham, Byung-Joo [3 ]
机构
[1] Gachon Univ, Dept Psychiat, Gil Med Ctr, Inchon, South Korea
[2] Soonchunhyang Univ, Dept Med Biosci, Grad Sch, Puchon, South Korea
[3] Korea Univ, Coll Med, Dept Psychiat, Seoul 136705, South Korea
[4] Korea Univ, Seoul, South Korea
[5] Kangwon Natl Univ, Coll Med, Neurosci Res Inst, Chunchon, South Korea
基金
新加坡国家研究基金会;
关键词
CHRONIC STRESS; GENE NR3C1; BRAIN; EXPRESSION; CORTISOL; SEGMENTATION; THICKNESS; SEVERITY; EXPOSURE; PROMOTER;
D O I
10.1371/journal.pone.0085425
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Background: DNA methylation in the promoter region of the glucocorticoid receptor gene (NR3C1) is closely associated with childhood adversity and suicide. However, few studies have examined NR3C1 methylation in relation to major depressive disorder (MDD) and hippocampal subfield volumes. We investigated the possible association between NR3C1 methylation and structural brain alterations in MDD in comparison with healthy controls. Methods: We compared the degree of NR3C1 promoter methylation in the peripheral blood of non-psychotic outpatients with MDD and that of healthy controls. Correlations among NR3C1 promoter methylation, structural abnormalities in hippocampal subfield volumes and whole-brain cortical thickness, and clinical variables were also analyzed. Results: In total, 117 participants (45 with MDD and 72 healthy controls) were recruited. Patients with MDD had significantly lower methylation than healthy controls at 2 CpG sites. In MDD, methylations had positive correlations with the bilateral cornu ammonis (CA) 2-3 and CA4-dentate gyrus (DG) subfields. However, in healthy controls, methylations had positive correlation with the subiculum and presubiculum. There were no differences in total and subfield volumes of the hippocampus between patients with MDD and healthy controls. Compared with healthy controls, patients with MDD had a significantly thinner cortex in the left rostromiddle frontal, right lateral orbitofrontal, and right pars triangularis areas. Conclusions: Lower methylation in the NR3C1 promoter, which might have compensatory effects relating to CA2-3 and CA4-DG, is a distinct epigenetic characteristic in non-psychotic outpatients with MDD. Future studies with a longitudinal design and a comprehensive neurobiological approach are warranted in order to elucidate the effects of NR3C1 methylation.
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页数:9
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