Tryptophan hydroxylase 2 gene is associated with major depression and antidepressant treatment response

• Published in: Progress in neuro-psychopharmacology & biological psychiatry Vol. 33; no. 4; pp. 637 - 641
• Main Authors: Tsai, Shih-Jen, Hong, Chen-Jee, Liou, Ying-Jay, Yu, Younger W-Y, Chen, Tai-Jui, Hou, Sheue-Jane, Yen, Feng-Chang
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 15.06.2009; Elsevier
• Subjects: Adult; Adult and adolescent clinical studies; Antidepressant; Antidepressive Agents - therapeutic use; Biological and medical sciences; Citalopram; Depression; Depressive Disorder, Major - drug therapy; Depressive Disorder, Major - genetics; Female; Fluoxetine; Gene Frequency; Genetic Predisposition to Disease; Genotype; Humans; Major depressive disorders; Male; Medical sciences; Middle Aged; Mood disorders; Neuropharmacology; Pharmacogenetics; Pharmacology. Drug treatments; Polymorphism; Polymorphism, Single Nucleotide - genetics; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychopharmacology; Serotonin Uptake Inhibitors - therapeutic use; Taiwan; Tryptophan Hydroxylase - genetics; Tryptophan hydroxylase 2; Asia; China; Taiwan; Antidepressant; Pharmacogenetics; MDD; TPH; SSRI; SNP; Tryptophan hydroxylase 2; LD; HPA; SCAN; CHB; HAM-D; Major depressive disorders; Polymorphism; Mood disorder; Genetic variability; Serotonin; Healthy subject; Fluoxetine; Psychotropic; Etiopathogenesis; Depression; Reuptake inhibitor; Selective serotonin reuptake inhibitor; Citalopram; Treatment; Gene; Genetics; Antidepressant agent; Comparative study
• ISSN: 0278-5846; 1878-4216; 1878-4216
• DOI: 10.1016/j.pnpbp.2009.02.020

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.