title: Association Study of Genotype by Depressive Response during Tryptophan Depletion in Subjects Recovered from Major Depression.
abstract: OBJECTIVE
  The brief and reversible mood response to acute tryptophan (TRP) depletion (ATD) is being studied as a trait marker in subjects considered at risk for major depression (MD).
  
  
  METHODS
  ATD was administered to 64 subjects (54 European-Americans, and10 from other races) with personal and family history of MD. They were in remission and had been medication-free for at least three months. Subjects received an active and sham condition in a random assignment, double-blind crossover design. They were genotyped for serotonin-related candidate genes, and mood response was quantified with the Hamilton Depression Rating Scale (HDRS). Data were analyzed using Poisson regression with repeated measures and latent trajectory models.
  
  
  RESULTS
  Compared to the sham control, active ATD caused modest depressive changes showing significant main effects of test condition (χ2=5.14, df=1, p=0.023) and time (χ2=12.22, df=3, p=0.007), but no significant interaction of time and test condition. Latent trajectory analysis revealed two groups, identified as depletion responders and non-responders. Those with theHTR2Ars6313 CC genotype had significantly higher HDRS scores during ATD (χ2=11.72, df=1, p=.0006).
  ATD may help the identification of biological subtypes of MD. These data are consistent with imaging reports implicating 5-HT2A receptor function in ATD phenotypes.
authors.affiliation: Department of Psychiatry, College of Medicine, The University of Arizona Health Sciences Center, USA.
authors.forename: Francisco A
authors.initials: FA
authors.lastname: Moreno
authors.affiliation: Department of Pediatrics, College of Medicine, The University of Arizona Health Sciences Center, USA.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Erickson
authors.affiliation: Division of Translational Research (DTR), National Institute of Mental Health, USA.
authors.forename: Holly A
authors.initials: HA
authors.lastname: Garriock
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, VA Connecticut Health Care Center, USA.
authors.forename: Joel
authors.initials: J
authors.lastname: Gelernter
authors.affiliation: Department of Psychiatry, University of Texas Health Sciences Center San Antonio, USA.
authors.forename: Jim
authors.initials: J
authors.lastname: Mintz
authors.affiliation: Department of Physiology, College of Medicine, The University of Arizona Health Sciences Center, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Oas-Terpstra
authors.affiliation: Health and Community Systems, University of Pittsburgh School of Nursing, USA.
authors.forename: Marilyn A
authors.initials: MA
authors.lastname: Davies
authors.affiliation: Department of Psychiatry, University of Arkansas for Medical Sciences, USA.
authors.forename: Pedro L
authors.initials: PL
authors.lastname: Delgado
keywords: Depression Endophenotype; Neurotransmitter Depletion; Serotonin Candidate Genes (SLC6A4, 5-HTTLPR, STin2, HTR1A, HTR2A, TPH2)