Variation in GNB3 predicts response and adverse reactions to antidepressants

Robert Keers, Cristian Bonvicini, Catia Scassellati, Rudolf Uher, Anna Placentino, Caterina Giovannini, Marcella Rietschel, Neven Henigsberg, Dejan Kozel, Ole Mors, Wolfgang Maier, Joanna Hauser, Daniel Souery, Julien Mendlewicz, Christine Schmäl, Astrid Zobel, Erik R Larsen, Aleksandra Szczepankiewicz, Zrnka Kovacic, Amanda ElkinIan Craig, Peter McGuffin, Anne E Farmer, Katherine J Aitchison, Massimo Gennarelli

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)


There is substantial inter-individual variation in response and adverse reactions to antidepressants, and genetic variation may, in part, explain these differences. GNB3 encodes the beta 3 subunit of the G protein complex, which is involved in the downstream signalling cascade following monoamine receptor activation. A functional polymorphism in this gene (C825T) has been associated with response to antidepressants. Several lines of evidence suggest that GNB3 moderates improvement in the neurovegetative symptoms of depression (such as sleep and appetite) and related adverse reactions independently of change in core mood symptoms. We here report analysis of data from GENDEP, a part-randomized pharmacogenomic trial, on the outcome of 811 subjects with major depression undergoing treatment with either escitalopram or nortriptyline in which the C825T SNP and three further SNPs in GNB3 were genotyped. The TT genotype was significantly associated with a superior response to nortriptyline and these effects were specific to improvements in neurovegetative symptoms. In addition, the same genotype predicted fewer incidents of treatment-emergent insomnia and greater weight gain on the same drug. Our results are consistent with previous associations with GNB3 and emphasize the importance of signalling genes in antidepressant response.
Original languageEnglish
Pages (from-to)867 - 874
Number of pages8
JournalJournal of Psychopharmacology
Issue number7
Publication statusPublished - Jul 2011


  • Adult
  • Antidepressive Agents
  • Citalopram
  • Depressive Disorder, Major
  • Europe
  • Female
  • Gene Frequency
  • Haplotypes
  • Heterotrimeric GTP-Binding Proteins
  • Humans
  • Linkage Disequilibrium
  • Male
  • Middle Aged
  • Nortriptyline
  • Pharmacogenetics
  • Polymorphism, Single Nucleotide
  • Psychiatric Status Rating Scales
  • Risk Assessment
  • Risk Factors
  • Sleep Initiation and Maintenance Disorders
  • Time Factors
  • Treatment Outcome
  • Weight Gain


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