Moderation of antidepressant response by the serotonin transporter gene.
BACKGROUND
There have been conflicting reports on whether the length polymorphism in the promoter of the serotonin transporter gene (5-HTTLPR) moderates the antidepressant effects of selective serotonin reuptake inhibitors (SSRIs). We hypothesised that the pharmacogenetic effect of 5-HTTLPR is modulated by gender, age and other variants in the serotonin transporter gene.


OBJECTIVE
To test the hypothesis that the 5-HTTLPR differently influences response to escitalopram (an SSRI) compared with nortriptyline (a noradrenaline reuptake inhibitor).


METHODS
The 5-HTTLPR and 13 additional markers across the serotonin transporter gene were genotyped in 795 adults with moderate-to-severe depression treated with escitalopram or nortriptyline in the Genome Based Therapeutic Drugs for Depression (GENDEP) project.


RESULTS
The 5-HTTLPR moderated the response to escitalopram, with long-allele carriers improving more than short-allele homozygotes. A significant three-way interaction between 5-HTTLPR, drug and gender indicated that the effect was concentrated in males treated with escitalopram. The single-nucleotide polymorphism rs2020933 also influenced outcome.


CONCLUSIONS
The effect of 5-HTTLPR on antidepressant response is SSRI specific conditional on gender and modulated by another polymorphism at the 5' end of the serotonin transporter gene.
Huezo-Diaz
Patricia
P
Institute of Psychiatry, King's College London, UK.
Uher
Rudolf
R
Smith
Rebecca
R
Rietschel
Marcella
M
Henigsberg
Neven
N
Marusic
Andrej
A
Mors
Ole
O
Maier
Wolfgang
W
Hauser
Joanna
J
Souery
Daniel
D
Placentino
Anna
A
Zobel
Astrid
A
Larsen
Erik Roj
ER
Czerski
Piotr M
PM
Gupta
Bhanu
B
Hoda
Farzana
F
Perroud
Nader
N
Farmer
Anne
A
Craig
Ian
I
Aitchison
Katherine J
KJ
McGuffin
Peter
P
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use; D015283:Citalopram / Q000627:therapeutic use*; D003866:Depressive Disorder / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009661:Nortriptyline / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use; D012737:Sex Factors; D055815:Young Adult
D000929:Antidepressive Agents, Tricyclic; D015283:Citalopram; D009661:Nortriptyline; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors