Tryptophan hydroxylase 2 gene is associated with major depression and antidepressant treatment response
- Resource Type
- Authors
- Chen-Jee Hong; Sheue-Jane Hou; Tai-Jui Chen; Younger W.-Y. Yu; Ying-Jay Liou; Shih-Jen Tsai; Feng-Chang Yen
- Source
- Progress in neuro-psychopharmacologybiological psychiatry. 33(4)
- Subject
- Adult
Male
Genotype
Serotonin reuptake inhibitor
Taiwan
Citalopram
Pharmacology
Tryptophan Hydroxylase
behavioral disciplines and activities
Polymorphism, Single Nucleotide
Gene Frequency
Fluoxetine
mental disorders
medicine
Humans
Genetic Predisposition to Disease
Biological Psychiatry
Depressive Disorder, Major
TPH2
Middle Aged
medicine.disease
Antidepressive Agents
Major depressive disorder
Antidepressant
Female
Reuptake inhibitor
Psychology
Pharmacogenetics
Selective Serotonin Reuptake Inhibitors
medicine.drug
- Language
- ISSN
- 1878-4216
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.