2 results
Association of glucocorticoid receptor polymorphisms with the susceptibility to major depressive disorder and treatment responses in Korean depressive patients
- Hwa-Young Lee, Rhee-Hun Kang, Sang-Woo Han, Jong-Woo Paik, Hun Soo Chang, Yoo Jung Jeong, Min-Soo Lee
-
- Journal:
- Acta Neuropsychiatrica / Volume 21 / Issue 1 / February 2009
- Published online by Cambridge University Press:
- 24 June 2014, pp. 11-17
-
- Article
- Export citation
-
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.
Method: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.
Conclusion: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.
5 - Pharmacogenetics of ethnic populations
-
- By Min-Soo Lee, Department of Psychiatry, Korea University College of Medicine, Seoul, Korea, Rhee-Hun Kang, Department of Psychiatry, College of Medicine, Korea University, Seoul, Korea, Sang-Woo Hahn, Department of Psychiatry, College of Medicine, Soonchunhyang University, Seoul, Korea
- Edited by Chee H. Ng, University of Melbourne, Keh-Ming Lin, Bruce S. Singh, University of Melbourne, Edmond Y. K. Chiu, University of Melbourne
-
- Book:
- Ethno-psychopharmacology
- Published online:
- 22 August 2009
- Print publication:
- 20 March 2008, pp 62-86
-
- Chapter
- Export citation
-
Summary
Introduction
Highly complex mechanisms underlie the variability in drug responses, which can be attributed to several physiological and environmental factors such as age, renal and liver function, nutritional status, smoking, and alcohol consumption. However, it has been established for almost half a century that genetic factors also influence both the efficacy of a drug and the likelihood of adverse reactions (Weinshilboum, 2003). Psychotropic drugs appear to be effective across cultures and ethnicities (Lin, Poland & Nakasaki, 1993, Lin, Tsai, Yu et al. 1999), but it is increasingly recognized that these responses also vary (Lin & Poland, 1995; Poolsup, Li Wan Po & Knight 2000). The discovery of widespread ethnospecific polymorphisms in genes governing pharmacokinetic and pharmacodynamic aspects of psychotropic drugs may explain some of these variations (Lin et al., 1999; Kalow, 1992).
Pharmacodynamic aspects
The term pharmacodynamics encompasses all the processes that influence the relationship between drug concentration and resulting effects. Psychotropic drugs have a wide variety of targets within neurotransmitter systems, including neurotransmitter synthesis, degradation of enzymes, storage, receptors, and specific transporter proteins.
Genetic studies of antidepressants
Serotonin transporter
The brain 5-HT transporter (5-HTT) is the principal site of action of many antidepressants. This transporter takes up 5-HT into the presynaptic neuron, thus terminating synaptic actions, and recycles it into the neurotransmitter pool. Ramamoorthy, Bauman, Moore et al. (1993) identified and cloned a single gene encoding the human 5-HTT, localized to chromosome 17q11.1∼q12, spanning 21 kb, and consisting of 14 exons (Lesch, Balling, Gross et al., 1994).