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.

This study investigated the possible effect of the –1438A/G single-nucleotide polymorphism in the promoter region of the serotonin 2A receptor (5-HTR2A) gene on major depressive disorder (MDD) in a Korean population. This polymorphism was analyzed in 189 patients with MDD and in 148 unrelated healthy controls using a case-control design, which revealed a significant difference in the genotype distributions (χ² = 10.78, d.f. = 2, p = 0.005). The frequency of the –1438G allele was also much higher in MDD patients than in normal controls (χ² = 7.20, p = 0.007; OR = 1.52, 95% CI 1.12–2.06). We also found significantly more carriers of the G allele (GG+AG genotypes) in MDD patients than in normal controls (χ² = 10.18, p = 0.001; OR = 2.46, 95% CI 1.40–4.32). Our results support the hypothesis that the –1438A/G polymorphism of the promoter region of the 5-HTR2A gene is associated with MDD patients in a Korean population.

The 5-HTR2A gene is a candidate gene for influencing the clinical response to antidepressant treatment. The purpose of this study was to determine the relationship between the –1438A/G polymorphism in the 5-HTR2A gene and the response to citalopram in a Korean population with major depressive disorder (MDD). Citalopram was administered for 4 weeks to the 71 patients who completed this study. We found significant differences in genotype, allele, and carrier distribution between the normal group and MDD patients (genotypes: χ² = 6.473, d.f. = 2, p = 0.039; alleles: χ² = 5.589, d.f. = 1, p = 0.018; OR = 0.618, 95% CI = 0.414–0.922; allele carriers: χ² = 5.383, d.f. = 1, p = 0.020; OR = 0.473, 95% CI = 0.249–0.879). The frequency of the –1438G allele was much higher in MDD patients than in the normal group (allele carriers: χ² = 5.383, d.f. = 1, p = 0.020; OR = 0.473, 95% CI = 0.249–0.879). There were also significant differences in response to citalopram according to the –1438A/G variation of 5-HTR2A in MDD patients. The group of remitters carried a higher frequency of the GG allele than of the AA and AG alleles. More of nonremitters carried the A allele than were without it (genotype: χ² = 8.016, p = 0.018; allele carrier: χ² = 4.512, p = 0.034; OR = 0.324, 95% CI = 0.112–0.936). The response to citalopram differed with the –1438A/G polymorphism genotype and allele carriers. The –1438G/–1438G genotype appeared to be associated with a better response to citalopram, with especially the G allele being related to core depressive symptoms and psychic anxiety improvement (p<0.05). These results suggest that the G allele of the –1438A/G polymorphism in the 5-HTR2A gene is associated with MDD, and that patients with –1438G/–1438G have a better response to citalopram treatment than patients with –1438A/–1438A or –1438A/–1438G.

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It has been suggested that the characteristics of alexithymia result from deficits in frontal lobe functioning, and the prefrontal cortex is particularly dependent on the catechol O-methyltransferase (COMT) pathway. We investigated the relationship between COMT Val108/158Met, serotonin transporter coding sequence (5-HT transporter gene-linked polymorphic region; 5-HTTLPR) polymorphisms, and alexithymia.The study sample comprised 109 students at the Korea University. All participants were tested using the 20-item Toronto Alexithymia Scale (TAS-20). They were genotyped for COMT Val108/158Met and 5-HTTLPR polymorphisms. Genotyping was analyzed using polymerase chain reaction. Subjects with Val/Val genotype had significantly higher TAS-20 scores than those with Met/Met or Met/Val genotypes. However, there was no significant relationship between the 5-HTTLPR genotype and TAS-20 scores. This indicates a possible association between the COMT Val108/158Met gene polymorphism and alexithymia.