title: Genomic predictors of remission to antidepressant treatment in geriatric depression using genome-wide expression analyses: a pilot study.
abstract: OBJECTIVE
  This first pilot study of genome-wide expression as predictor of antidepressant response in late-life depression examined genome-wide transcriptional profiles in a randomized placebo-controlled trial of combined methylphenidate and citalopram.
  
  
  METHODS
  Genome-wide transcriptional profiles were examined in peripheral blood leukocytes sampled at baseline and 16 weeks from 35 older adults with major depression, who were randomized to methylphenidate + citalopram, citalopram + placebo, or methylphenidate + placebo. Methylphenidate doses ranged between 10 and 40 mg/day, and citalopram doses ranged between 20 and 60 mg/day. Remission was defined as Hamilton Depression Rating Scale score of 6 or below. Early remission was achieved in the first 4 weeks of treatment. We hypothesized that differential gene expression at baseline can predict antidepressant response.
  
  
  RESULTS
  We analyzed gene expression in 24 remitters and 11 non-remitters. At baseline, we found three genes showing higher expression in all remitters versus non-remitters that satisfied the established level of significance: a fold change of 2 and p-value of 0.05 that included HLA-DRB5, SELENBP1, and LOC388588. Two gene transcripts showed higher expression in early remitters at baseline compared with non-remitters. The first gene was CA1 carbonic anhydrase gene, on chromosome 8 involved in respiratory function (fold change 2.54; p = 0.03). The second gene was the SNCA-α-synuclein gene, implicated, which binds to dopamine transporter (fold change 2.1; p = 0.03).
  
  
  CONCLUSIONS
  Remission to antidepressants in geriatric depression may be associated with a particular gene expression profile in monoaminergic and metabolic pathways and needs to be replicated in a larger sample.
authors.affiliation: Discipline of Psychiatry, University of Adelaide, Adelaide, South Australia, Australia.|UCLA Semel Institute for Neuroscience and Human Behavior, UCLA, Los Angeles, CA, USA.
authors.forename: Harris A
authors.initials: HA
authors.lastname: Eyre
authors.affiliation: Department of Human Genetics, UCLA, Los Angeles, CA, USA.
authors.forename: Ascia
authors.initials: A
authors.lastname: Eskin
authors.affiliation: Department of Human Genetics, UCLA, Los Angeles, CA, USA.
authors.forename: Stanley F
authors.initials: SF
authors.lastname: Nelson
authors.affiliation: UCLA Semel Institute for Neuroscience and Human Behavior, UCLA, Los Angeles, CA, USA.
authors.forename: Natalie M
authors.initials: NM
authors.lastname: St Cyr
authors.affiliation: UCLA Semel Institute for Neuroscience and Human Behavior, UCLA, Los Angeles, CA, USA.
authors.forename: Prabha
authors.initials: P
authors.lastname: Siddarth
authors.affiliation: Discipline of Psychiatry, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Bernhard T
authors.initials: BT
authors.lastname: Baune
authors.affiliation: UCLA Semel Institute for Neuroscience and Human Behavior, UCLA, Los Angeles, CA, USA.
authors.forename: Helen
authors.initials: H
authors.lastname: Lavretsky
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000928:Antidepressive Agents / Q000627:therapeutic use*; D015283:Citalopram / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000235:genetics*; D018765:Dopamine Uptake Inhibitors / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D060828:Induction Chemotherapy; D008297:Male; D008774:Methylphenidate / Q000627:therapeutic use*; D008875:Middle Aged; D010865:Pilot Projects; D011569:Psychiatric Status Rating Scales
chemical_list: D000928:Antidepressive Agents; D018765:Dopamine Uptake Inhibitors; D015283:Citalopram; D008774:Methylphenidate
keywords: antidepressant response; citalopram; gene expression; geriatric depression; methylphenidate; remission