Age-dependent antidepressant pharmacogenomics: polymorphisms of the serotonin transporter and G protein beta3 subunit as predictors of response to fluoxetine and nortriptyline.
In 169 depressed patients randomized to treatment with either fluoxetine or nortriptyline, we examined whether polymorphisms of the serotonin transporter and the G protein beta3 subunit influenced response to these antidepressants. For depressed patients under the age of 25 yr the T allele of the G protein beta3 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 beta3 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.
Joyce
Peter R
PR
Department of Psychological Medicine, Christchurch School of Medicine and Health Sciences, P.O. Box 4345, Christchurch, New Zealand. peter.joyce@chmeds.ac.nz
Mulder
Roger T
RT
Luty
Suzanne E
SE
McKenzie
Janice M
JM
Miller
Allison L
AL
Rogers
Geraldine R
GR
Kennedy
Martin A
MA
D000328:Adult; D000367:Age Factors; D000483:Alleles; D018687:Antidepressive Agents, Second-Generation / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000929:Antidepressive Agents, Tricyclic / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D005473:Fluoxetine / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D044387:GTP-Binding Protein beta Subunits / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009661:Nortriptyline / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010552:Personality Assessment; D010555:Personality Inventory; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D011379:Prognosis; D050486:Serotonin Plasma Membrane Transport Proteins; D016896:Treatment Outcome
D018687:Antidepressive Agents, Second-Generation; D000929:Antidepressive Agents, Tricyclic; D002352:Carrier Proteins; D044387:GTP-Binding Protein beta Subunits; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D005473:Fluoxetine; D009661:Nortriptyline