Association of glucocorticoid receptor polymorphisms with the susceptibility to major depressive disorder and treatment responses in Korean depressive patients.
OBJECTIVE
Major depressive disorder (MDD) is closely related to stress reactions and serotonin probably underpins the pathophysiology of MDD. Alterations of the hypothalamic-pituitary-adrenal axis at the gene level have reciprocal consequences on serotonin neurotransmission. Glucocorticoid receptor (GR) polymorphisms affect glucocorticoid sensitivity, which is associated with cortisol feedback effects. Therefore, we hypothesised that GR polymorphisms are associated with the susceptibility to MDD and predict the treatment response.


METHODS
Ninety-six subjects with a minimum score of 17 on the 21-item Hamilton Depression Scale (HAMD) at baseline were enrolled into the present study. The genotypes of GR (N363S, ER22/23EK, Bcl1, and TthIII1 polymorphisms) were analysed. The HAMD score was again measured after 1, 2, 4 and 8 weeks of antidepressant treatment to detect whether the therapeutic effects differed with the GR genotype.


RESULTS
Our subjects carried no N363S or ER22/23EK genetic polymorphisms and three types of Bcl1 and TthIII1 genetic polymorphisms. The C/C genotype and C allele at Bcl1 polymorphism were more frequent in MDD patients than in normal controls (p < 0.01 and p = 0.01, respectively). The genotype distributions did not differ significantly between responders and non-responders.


CONCLUSIONS
These results suggest that GR polymorphism cannot predict the therapeutic response after antidepressant administration. However, GR polymorphism (Bcl1) might play a role in the pathophysiology of MDD. Future studies should check this finding in larger populations with different characteristics.
1Clinical Research Center for Depression, Korea University, Seoul, Korea.
Hwa-Young
HY
Lee
1Clinical Research Center for Depression, Korea University, Seoul, Korea.
Rhee-Hun
RH
Kang
4Department of Psychiatry, College of Medicine, Soonchunhyang University, Seoul, Korea.
Sang-Woo
SW
Han
5Department of Psychiatry, College of Medicine, Kyunghee University, Seoul, Korea.
Jong-Woo
JW
Paik
1Clinical Research Center for Depression, Korea University, Seoul, Korea.
Hun Soo
HS
Chang
1Clinical Research Center for Depression, Korea University, Seoul, Korea.
Yoo Jung
YJ
Jeong
1Clinical Research Center for Depression, Korea University, Seoul, Korea.
Min-Soo
MS
Lee