The International Journal of Neuropsychopharmacology



Age-dependent antidepressant pharmacogenomics: polymorphisms of the serotonin transporter and G protein β3 subunit as predictors of response to fluoxetine and nortriptyline


Peter R. Joyce a1c1, Roger T. Mulder a1, Suzanne E. Luty a1, Janice M. McKenzie a1, Allison L. Miller a2, Geraldine R. Rogers a2 and Martin A. Kennedy a2
a1 Department of Psychological Medicine, Christchurch School of Medicine and Health Sciences, P.O. Box 4345, Christchurch, New Zealand
a2 Department of Pathology, Christchurch School of Medicine and Health Sciences, P.O. Box 4345, Christchurch, New Zealand

Article author query
joyce p   [PubMed][Google Scholar] 
mulder r   [PubMed][Google Scholar] 
luty s   [PubMed][Google Scholar] 
mckenzie j   [PubMed][Google Scholar] 
miller a   [PubMed][Google Scholar] 
rogers g   [PubMed][Google Scholar] 
kennedy m   [PubMed][Google Scholar] 

Abstract

In 169 depressed patients randomized to treatment with either fluoxetine or nortriptyline, we examined whether polymorphisms of the serotonin transporter and the G protein β3 subunit influenced response to these antidepressants. For depressed patients under the age of 25 yr the T allele of the G protein β3 subunit was associated with a markedly poorer response to nortriptyline, while serotonin transporter polymorphisms did not predict antidepressant response. However, in patients 25 yr or older, the G protein β3 polymorphisms did not predict antidepressant response, while the s,s genotype of the serotonin transporter was associated with a poorer response to both fluoxetine and nortriptyline. These differential pharmacogenetic predictors of antidepressant response by age, may provide clues to understanding the discontinuities in pharmacological responsiveness of child/adolescent and adult depressive disorders.

(Received September 9 2002)
(Reviewed January 15 2003)
(Revised April 2 2003)
(Accepted April 6 2003)


Key Words: Antidepressants; G protein β3 subunit; pharmacogenomics; serotonin transporter.

Correspondence:
c1 Professor P. R. Joyce, Department of Psychological Medicine, Christchurch School of Medicine and Health Sciences, P.O. Box 4345, Christchurch, New Zealand. Tel.: ++64 3 3720 404 Fax: ++64 3 3720 407 E-mail: peter.joyce@chmeds.ac.nz