title: Role of COMT, 5-HT(1A) , and SERT genetic polymorphisms on antidepressant response to Transcranial Magnetic Stimulation.
abstract: BACKGROUND
  Transcranial Magnetic Stimulation (TMS) is an effective technique in the treatment of depression, specifically in drug-resistant patients. However, there is little data available on the influence of genetic variables on TMS response.
  
  
  METHODS
  We analyzed the role of three genetic polymorphisms that affected the antidepressant response: serotonin transporter promoter region (SERTPR) polymorphism, 5-HT(1A) serotonergic receptor promoter region polymorphism (rs6295), and the coding region of COMT gene polymorphism (rs4680). Ninety patients with a major depressive drug-resistant episode due to a Major Depressive Disorder or to a Bipolar Disorder were included in our study. Patients underwent high frequency TMS, focused on the left prefrontal cortex, for 2 weeks. At study completion, the response rate was 45.5%. Effects of gene polymorphisms on clinical improvement were analyzed with an analysis of variance with each gene (SERTPR, 5-HT(1A) , and COMT) as factors and the Hamilton Rating Scale for Depression variation from baseline to the end of the treatment as a dependent variable.
  
  
  RESULTS
  We found a significant model in which three factors were not significant (diagnosis, COMT, and SERTPR), whereas factor 5-HT(1A) showed a significant influence on the outcome, with patients with C/C genotype showing a greater improvement than G/G and C/G and no difference between G/G and C/G.
  
  
  CONCLUSIONS
  According to our data, 5-HT(1A) polymorphism may play a role in influencing TMS response. The effect of COMT and SERTPR did not reach statistical significance. The analysis of these and other candidate genes in larger samples could help explain genetic influence on TMS response.
authors: San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Clinical Neurosciences Department, Milan, Italy.
authors: Alessia
authors: A
authors: Malaguti
authors: David
authors: D
authors: Rossini
authors: Adelio
authors: A
authors: Lucca
authors: Lorenzo
authors: L
authors: Magri
authors: Cristina
authors: C
authors: Lorenzi
authors: Adele
authors: A
authors: Pirovano
authors: Christina
authors: C
authors: Colombo
authors: Enrico
authors: E
authors: Smeraldi
authors: Raffaella
authors: R
authors: Zanardi
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D001714:Bipolar Disorder / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology / Q000628:therapy*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology / Q000628:therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016366:Open Reading Frames / Q000235:genetics; D010555:Personality Inventory / Q000706:statistics & numerical data; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011594:Psychometrics; D044263:Receptors, Serotonin, 5-HT1 / Q000235:genetics*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D050781:Transcranial Magnetic Stimulation; D016896:Treatment Outcome
chemical_list: D044263:Receptors, Serotonin, 5-HT1; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D002394:Catechol O-Methyltransferase