title: SLC6A4 polymorphisms and age of onset in late-life depression on treatment outcomes with citalopram: a Sequenced Treatment Alternatives to Relieve Depression (STAR*D) report.
abstract: OBJECTIVE
  Age at onset of first major depressive episode (MDE) does not necessarily translate into different treatment outcomes to antidepressants in late-life depression. The influence of genetic variants may affect this relationship.
  
  
  METHODS
  Post hoc data set analysis of the association between variants in the promoter region (indel, rs25531) and within intron 2 (Stin2 VNTR) of the SCL6A4 gene and treatment outcomes among older participants in the first treatment arm of the Sequenced Treatment Alternatives to Relieve Depression trial (STAR*D).
  
  
  METHODS
  Participants were enrolled from 23 psychiatric and 18 primary care settings.
  
  
  METHODS
  Two hundred twenty-one, white non-Hispanic subjects, aged 60 to 75 years, with 16-item Quick Inventory of Depressive Symptomatology-Clinician Rating (QIDS-CR16) initial score ≥10, and who remained in the study for at least 6 weeks, were genotyped.
  
  
  METHODS
  Citalopram treatment for up to 14 weeks.
  
  
  METHODS
  Main outcome was remission rate defined as a score of ≤5 on the QIDS-CR16. Response was a secondary outcome defined as a reduction of ≥50% of baseline QIDS-CR16.
  
  
  RESULTS
  Polymorphism in the indel promoter region was associated with remission among subjects whose first lifetime episode of major depression occurred later than age 55. In this group, subjects with L/L genotype had significantly higher remission (80% versus 43%) compared to those subjects with any other indel promoter genotype. Multivariate analysis demonstrated that the genetic effect of the indel promoter region on remission increases along with age at onset of MDE.
  
  
  CONCLUSIONS
  Variants in the indel promoter region of the SLC6A4 gene have a more robust effect to antidepressant outcome among older subjects who experienced their first MDE at a later age. The mechanism of action of these variants remains to be determined.
authors: Geriatric Psychiatry Clinic, Mental Health Service Line, Minneapolis VA Medical Center, University of Minnesota Medical School, Minneapolis, MN. Electronic address: paulo.shiroma@va.gov.
authors: Paulo R
authors: PR
authors: Shiroma
authors: Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN.
authors: Maureen S
authors: MS
authors: Drews
authors: Department of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN.
authors: Jennifer R
authors: JR
authors: Geske
authors: Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN.
authors: David A
authors: DA
authors: Mrazek
mesh_terms: D017668:Age of Onset; D000368:Aged; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use*; D015283:Citalopram / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D018687:Antidepressive Agents, Second-Generation; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D015283:Citalopram
keywords: Depression; SLC6A4; Sequenced Treatment Alternatives to Relieve Depression (STAR*D); citalopram
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