Tryptophan hydroxylase 2 gene is associated with major depression and antidepressant treatment response.
Tryptophan hydroxylase-2 (TPH2) is the rate-limiting biosynthetic isoenzyme for serotonin that is preferentially expressed in the brain and has been implicated in the pathogenesis of major depressive disorder (MDD) and in the mechanism of antidepressant action. This study aimed to investigate whether common genetic variation in the TPH2 gene is associated with MDD and therapeutic response to antidepressants in a Chinese population. A total of 508 MDD patients and 463 unrelated controls were recruited. Among the MDD patients, 187 accepted selective serotonin reuptake inhibitor (fluoxetine or citalopram) antidepressant treatment for 8 weeks with therapeutic evaluation before and after treatment. Five TPH2 polymorphisms were genotyped and their association with MDD or treatment response was assessed by haplotype and single-marker analysis. In single-marker-based analysis, the rs17110747-G homozygote polymorphism was found to be more frequent in the MDD patients than in the controls (P=0.002). Genotype analysis in responders (defined as those with a 50% reduction in baseline Hamilton score) and non-responders after 8 weeks of antidepressant treatment showed that the proportion of rs2171363 heterozygote carriers was higher in the responders than the non-responders (P=0.009). No significant association with MDD or antidepressant therapeutic response was discovered in haplotype analyses. Our findings show that TPH2 genetic variants may play a role in MDD susceptibility and in acute therapeutic response to selective serotonin reuptake inhibitors.
Tsai
Shih-Jen
SJ
Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan. sjtsai@vghtpe.gov.tw
Hong
Chen-Jee
CJ
Liou
Ying-Jay
YJ
Yu
Younger W-Y
YW
Chen
Tai-Jui
TJ
Hou
Sheue-Jane
SJ
Yen
Feng-Chang
FC
D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use*; D015283:Citalopram; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D005473:Fluoxetine; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D013624:Taiwan; D014365:Tryptophan Hydroxylase / Q000235:genetics*
D000928:Antidepressive Agents; D015283:Citalopram; D005473:Fluoxetine; D017367:Selective Serotonin Reuptake Inhibitors; D014365:Tryptophan Hydroxylase; C494784:TPH2 protein, human