Role of the serotonin transporter gene locus in the response to SSRI treatment of major depressive disorder in late life

Davide Seripa, Andrea Pilotto, Giulia Paroni, Andrea Fontana, Grazia D'Onofrio, Carolina Gravina, Maria Urbano, Leandro Cascavilla, Francesco Paris, Francesco Panza, Alessandro Padovani, Alberto Pilotto

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It has been suggested that the serotonin or 5-hydroxytriptamine (5-HT) transporter (5-HTT) and its gene-linked polymorphic region (5-HTTLPR) are selective serotonin reuptake inhibitor (SSRI) response modulators in late-life depression (LLD), and particularly in late-life major depressive disorder (MDD). Previous studies differed in design and results. Our study aimed to investigate the solute carrier family 6 (neurotransmitter transporter and serotonin) member 4 (SLC6A4) gene locus, encoding 5-HTT and SSRI treatment response in late-life MDD. For a prospective cohort study, we enrolled 234 patients with late-life MDD to be treated with escitalopram, sertraline, paroxetine or citalopram for 6 months. The SLC6A4 polymorphisms rs4795541 (5-HTTLPR), rs140701 and rs3813034 genotypes spanning the SLC6A4 locus were investigated in blinded fashion. No placebo group was included. We assessed responder or non-responder phenotypes according to a reduction in the 21-item version of the Hamilton Depression Rating Scale (HDRS-21) score of 50%. At follow-up, 30% of the late-life MDD patients were non-responders to SSRI treatment. No time-course of symptoms and responses was made. A poor response was associated with a higher baseline HDRS-21 score. We observed a significant over-representation of the rs4795541-S allele in the responder patients (0.436 versus 0.321; p = 0.023). The single S-allele dose-additive effect had OR = 1.74 (95% CI 1.12-2.69) in the additive regression model. Our findings suggested a possible influence of 5-HTTLPR on the SSRI response in patients with late-life MDD, which is potentially useful in identifying the subgroups of LLD patients whom need a different pharmacological approach.

Original languageEnglish
Pages (from-to)623-633
Number of pages11
JournalJournal of Psychopharmacology
Issue number5
Publication statusPublished - May 5 2015


  • Antidepressant drug resistance
  • depression
  • depression management
  • gene polymorphisms
  • geriatrics
  • late-life depression
  • major depressive disorder
  • selective serotonin reuptake inhibitor
  • solute carrier family 6

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Psychiatry and Mental health


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