Catecholamine pathway polymorphisms and antidepressant response

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Abstract

Introduction:

Genes that regulate the catecholamine metabolism pathways are potential targets for research in the antidepressant treatment response. This study was intended to determine whether antidepressant responses to selective serotonin reuptake inhibitors (SSRIs) are associated with genetic polymorphisms of the tyrosine or tryptophan gene in Chinese major depressive disorder (MDD) patients.

Methods:

A total of 290 MDD patients were recruited and received a 6-week SSRIs randomized double-blinded treatment. Allele, genotype, and haplotype frequencies were compared between responders and nonresponders in catecholamine genes.

Results:

Genotype frequency of the rs1800544 polymorphism in the DRD4 gene was significantly different between responders and nonresponders after false discovery rate correction (P = 0.042). The frequency of the DRD4 rs1800544 CG genotype was significantly higher (P = 0.003) in responders (51.4%) than in nonresponders (35.8%), and patients with the CG genotype showed an 81.7% response rate. In comparison, the response rates were 73.9% and 52.2% in patients with the GG genotype and the CC genotype, respectively. The frequencies of the DRD4 rs1800544 CC and GG genotypes were significantly lower (P = 0.003) in responders (7.7%, 40.9%) than in the nonresponders (19.4%, 44.8%). No significant difference was found between two groups either in genotype or allele frequencies of single nucleotide polymorphisms in the TPH, SLC6A2, SLC6A3, or DRD2 genes. No significant difference was found between two groups in TPH, SLC6A2, SLC6A3, DRD2, orDRD4 gene haplotypes.

Discussion:

Polymorphisms of the DRD4 gene appear to be associated with SSRI treatment response in Chinese MDD patients.

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