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

Abstract

BackgroundDNA 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.MethodsWe 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.ResultsIn 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.ConclusionsLower 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.

Corticosteroid receptor genes and childhood neglect influence susceptibility to crack/cocaine addiction and response to detoxification treatment

“…Additionally, changes in the HPA axis induced by childhood trauma and poor parental care perception were related to cocaine use during adulthood (Gerra et al, 2009;Gerra et al, 2010). The robust evidence of epigenetic changes occurring in GR and MR coding genes reinforce the possibility of gene-environmental interactions (Harris et al, 2013;Joels et al, 2008;Lian et al, 2014;Na et al, 2014;van der Knaap et al, 2014;Yehuda et al, 2014aYehuda et al, , 2014b. However, studies designed to evaluate this issue are scarce in crack/cocaine addiction.…”

Effects of the Social Environment and Stress on Glucocorticoid Receptor Gene Methylation: A Systematic Review

“…In addition, 8 studies examined the effects of psychopathologies on human GR gene methylation. Specifically, studies included response to stress (51), borderline personality disorder (52), bulimia nervosa (21), post-traumatic stress disorder (PTSD) (53–55) and depression (30, 56) (table 3). …”

The role of pro-inflammatory cytokines in neuroinflammation, neurogenesis and the neuroendocrine system in major depression

“…However, the results are inconsistent. Whereas several studies have reported hippocampal volumetric reduction in depression (Bremner et al, 2000), differences in hippocampal volume between patients with depression and controls have not been found in other studies (Na et al, 2014a;Vakili et al, 2000). Investigation of other brain regions involved in the regulation of cognition and emotion, such as the prefrontal cortex, the insula, and the occipital cortex, is needed (Price and Drevets, 2010).…”