Association between glucocorticoid receptor methylation and hippocampal subfields in major depressive disorder.
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.
Department of Psychiatry, Gachon University Gil Medical Center, Incheon, Republic of Korea.
Kyoung-Sae
KS
Na
Department of Medical Bioscience, Graduate school, Soonchunhyang University, Bucheon, Republic of Korea.
Hun Soo
HS
Chang
Department of Psychiatry, College of Medicine, Korea University, Seoul, Republic of Korea.
Eunsoo
E
Won
Department of Psychiatry, College of Medicine, Korea University, Seoul, Republic of Korea.
Kyu-Man
KM
Han
Brain and Cognitive engineering, Korea University, Seoul, Republic of Korea.
Sunyoung
S
Choi
Neuroscience Research Institute, College of Medicine, Kangwon National University, Chuncheon, Republic of Korea.
Woo Suk
WS
Tae
Department of Psychiatry, College of Medicine, Korea University, Seoul, Republic of Korea.
Ho-Kyoung
HK
Yoon
Department of Psychiatry, College of Medicine, Korea University, Seoul, Republic of Korea.
Yong-Ku
YK
Kim
Department of Psychiatry, College of Medicine, Korea University, Seoul, Republic of Korea.
Sook-Haeng
SH
Joe
Department of Psychiatry, College of Medicine, Korea University, Seoul, Republic of Korea.
In-Kwa
IK
Jung
Department of Psychiatry, College of Medicine, Korea University, Seoul, Republic of Korea.
Min-Soo
MS
Lee
Department of Psychiatry, College of Medicine, Korea University, Seoul, Republic of Korea.
Byung-Joo
BJ
Ham
D000293:Adolescent; D000328:Adult; D000368:Aged; D056651:CA2 Region, Hippocampal / Q000378:metabolism* / Q000503:physiopathology; D056654:CA3 Region, Hippocampal / Q000378:metabolism* / Q000503:physiopathology; D016022:Case-Control Studies; D019175:DNA Methylation; D018891:Dentate Gyrus / Q000378:metabolism* / Q000503:physiopathology; D003865:Major Depressive Disorder / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D011965:Receptors, Glucocorticoid / Q000235:genetics* / Q000378:metabolism
C497713:NR3C1 protein, human; D011965:Receptors, Glucocorticoid