Analysis of COMT gene (Val 158 Met polymorphism) in the clinical response to SSRIs in depressive patients of European origin.
OBJECTIVE
There is convincing evidence of interactions between serotonergic and dopaminergic systems and it seems that an increase of dopamine concentration in the whole brain could be a limiting factor for the antidepressant like effect of antidepressants. The COMT gene might be a good candidate for explaining some aspects of the pharmacological response to SSRIs.


METHODS
The aim of our study was to analyse the Val 158 Met functional polymorphism on COMT gene and clinical response (4 weeks) and clinical remission (6/8 and 12 weeks) in two samples of depressive patients (DSM-IV) treated with SSRIs of Italian and Spanish origin. Clinical outcome was measured using 21 items Hamilton scale, weekly in the Italian sample (along 6 weeks) and monthly in the Spanish one (along 12 weeks).


RESULTS
No overall effect of genotype or genotypextime interaction was detected. However, we observed a genotypextime interaction on HDRS decrease for citalopram treatment (F((4.6,317.5)) = 3.38, P = 0.007) in the Spanish sample. No clear effect was observed in the Italian sample. The three samples were pooled in order to test if carrying the Met/Met genotype confers an increased risk for non-remission at 6-8 weeks. The results showed that Met/Met carriers have an odds ratio of 2.21 (95% CI [1.20-4.12]) for non-remission (chi(2) = 7.43, df = 2, P = 0.006). The Met/Met effect was not observed in response at 4th week (for all SSRI treatments) or in remission at 12th week (citalopram treatment).


CONCLUSIONS
COMT gene could have a small and indirect effect of clinical response to SSRIs by slowing-down the antidepressant action along the follow-up, basically in citalopram treatment.
Arias
Bárbara
B
Unitat d'Antropologia, Departament de Biologia Animal, Facultat de Biologia, Universitat de Barcelona, Diagonal 645, 08028 Barcelona, Spain. barbara.arias@ub.edu
Serretti
Alessandro
A
Lorenzi
Cristina
C
Gastó
Cristóbal
C
Catalán
Rosa
R
Fañanás
Lourdes
L
D018687:Antidepressive Agents, Second-Generation / Q000009:adverse effects / Q000627:therapeutic use*; D001682:Biological Availability; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D015283:Citalopram / Q000009:adverse effects / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics* / Q000503:physiopathology / Q000523:psychology; D004298:Dopamine / Q000378:metabolism; D005006:Ethnicity / Q000235:genetics; D005260:Female; D016666:Fluvoxamine / Q000009:adverse effects / Q000627:therapeutic use*; D005500:Follow-Up Studies; D005625:Frontal Lobe / Q000187:drug effects / Q000503:physiopathology; D006580:Genetic Carrier Screening; D005838:Genotype; D006801:Humans; D008297:Male; D008715:Methionine / Q000235:genetics*; D017374:Paroxetine / Q000009:adverse effects / Q000627:therapeutic use*; D010555:Personality Inventory; D011110:Polymorphism, Genetic / Q000235:genetics*; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014633:Valine / Q000235:genetics*
D018687:Antidepressive Agents, Second-Generation; D002394:Catechol O-Methyltransferase; D015283:Citalopram; D004298:Dopamine; D016666:Fluvoxamine; D008715:Methionine; D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors; D014633:Valine