Genetic influence on response to serotonergic antidepressants

R. Zanardi, F. Benedetti, A. Serretti, E. Smeraldi

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

The mechanism of action of selective serotonin reuptake inhibitors (SSRIs) involves the block of the neuronal serotonin transporter (5-HTT). A functional polymorphism in the transcriptional control region upstream of the 5-HTT coding sequence has been recently reported. The long and short variants of this 5-HTT gene-linked polymorphic region (5-HTTLPR) have different transcriptional efficiencies, with the basal transcription of the long variant being more than twice that of the short form. Previous studies showed that the differences in 5-HTT mRNA synthesis resulted in different 5-HTT expression and 5-HT cellular uptake; that 5-HTT binding and 5-HTT mRNA levels varied significantly by 5-HTTLPR genotype; and that 5-HTTLPR influenced whole blood 5-HT content. Since 5-HTT is the primary target of action for SSRIs, we hypothesized that allelic variation of 5-HTT gene expression could influence the individual response to these drugs. In a sample of 166 inpatients, we observed that the efficacy of fluvoxamine in the treatment of delusional depression and the efficacy of paroxetine in the treatment of non-delusional depression was influenced by 5-HTTLPR polymorphism. Homozygotes for the long variant and heterozygotes showed better clinical responses than homozygotes for the short variant.

Original languageEnglish
Pages (from-to)538
Number of pages1
JournalAmerican Journal of Medical Genetics - Neuropsychiatric Genetics
Volume96
Issue number4
Publication statusPublished - Aug 7 2000

Fingerprint

Antidepressive Agents
Serotonin Uptake Inhibitors
Homozygote
Genes
Serotonin
Fluvoxamine
Paroxetine
Serotonin Plasma Membrane Transport Proteins
Messenger RNA
Heterozygote
Inpatients
Genotype
Gene Expression
Therapeutics
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Genetics(clinical)
  • Neuropsychology and Physiological Psychology
  • Neuroscience(all)

Cite this

Genetic influence on response to serotonergic antidepressants. / Zanardi, R.; Benedetti, F.; Serretti, A.; Smeraldi, E.

In: American Journal of Medical Genetics - Neuropsychiatric Genetics, Vol. 96, No. 4, 07.08.2000, p. 538.

Research output: Contribution to journalArticle

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