No association of TPH1 218A/C polymorphism with treatment response and intolerance to SSRIs in Japanese patients with major depression.
BACKGROUND
Variability in antidepressant response is due to genetic and environmental factors. Since SSRIs exert their activity enhancing the serotonin turnover, genes coding for proteins of the serotonin system are key candidates for a possible genetic influence with response to SSRIs. Therefore tryptophan hydroxylase (TPH), the rate-limiting enzyme in the biosynthesis of serotonin in the raphe nuclei could be a candidate. In the present study, we examined the possible association of the TPH1 218A/C polymorphism with response to SSRIs in a sample of Japanese patients with major depression.


METHODS
The 21-item Hamilton Rating Scale for Depression (HAM-D) was administered to evaluate depressive symptoms at baseline and bi-weekly over 6 weeks of treatment. All patients were genotyped for the TPH1 218A/C polymorphism.


RESULTS
Repeated-measures analysis of variance of HAM-D score change over time with baseline scores and 5-HTTLPR variants included in the model as covariate showed no significant association of this SNP with treatment response to SSRIs. Furthermore, no significant association of this SNP could be observed with both responder rate at weeks 2, 4 and 6 and intolerance to SSRIs.


CONCLUSIONS
The result suggests that 218A/C variants of TPH1 cannot play a major role as predictor of treatment response as well as intolerance in Japanese patients with major depression.
Kato
Masaki
M
Institute of Psychiatry, University of Bologna, Bologna, Italy. masaki.kato@unibo.it
Wakeno
Masataka
M
Okugawa
Gaku
G
Fukuda
Tsuyoshi
T
Azuma
Junichi
J
Kinoshita
Toshihiko
T
Serretti
Alessandro
A
D000328:Adult; D000704:Analysis of Variance; D000928:Antidepressive Agents / Q000097:blood / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011110:Polymorphism, Genetic; D017367:Selective Serotonin Reuptake Inhibitors / Q000097:blood / Q000627:therapeutic use*; D012720:Severity of Illness Index; D014365:Tryptophan Hydroxylase / Q000235:genetics*
D000928:Antidepressive Agents; D017367:Selective Serotonin Reuptake Inhibitors; D014365:Tryptophan Hydroxylase