title: Age-dependent antidepressant pharmacogenomics: polymorphisms of the serotonin transporter and G protein beta3 subunit as predictors of response to fluoxetine and nortriptyline.
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 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.
authors: Department of Psychological Medicine, Christchurch School of Medicine and Health Sciences, P.O. Box 4345, Christchurch, New Zealand. peter.joyce@chmeds.ac.nz
authors: Peter R
authors: PR
authors: Joyce
authors: Roger T
authors: RT
authors: Mulder
authors: Suzanne E
authors: SE
authors: Luty
authors: Janice M
authors: JM
authors: McKenzie
authors: Allison L
authors: AL
authors: Miller
authors: Geraldine R
authors: GR
authors: Rogers
authors: Martin A
authors: MA
authors: Kennedy
mesh_terms: 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
chemical_list: 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