title: Effect of tryptophan depletion on smokers and nonsmokers with and without history of major depression.
abstract: BACKGROUND
  Serotonergic dysregulation is posited to contribute to comorbidity between nicotine dependence and depression. We tested whether acute tryptophan depletion (ATD) triggers depressive symptoms in euthymic, unmedicated smokers and nonsmokers with and without history of major depressive disorder (MDD).
  
  
  METHODS
  Acute tryptophan depletion and taste-matched placebo challenges were administered double-blind in counter-balanced order. Participants were four groups of volunteers hypothesized to be of increasing affective vulnerability as follows: nonsmokers lacking recurrent personal and familial history of MDD (n = 20), smokers lacking recurrent personal and familial history of MDD (n = 21), nonsmokers with history of recurrent personal and familial MDD (n = 16), and smokers with recurrent personal and familial history of MDD (n = 16). Depression, dysphoric mood, and plasma amino acids were measured at baseline and around the time of peak depletion.
  
  
  RESULTS
  Depressive symptom response to ATD was heightened significantly by history of MDD (p < .001) and marginally by smoking (p = .09). Smoking seemed to magnify the ATD response of those with a history of MDD (effect size = .63) but had no effect on those without MDD history (effect size = .06).
  
  
  CONCLUSIONS
  Depressive symptom response to serotonergic challenge is exaggerated in unmedicated, euthymic adults with recurrent personal and familial vulnerability to MDD, perhaps especially if they also smoke.
authors.affiliation: Medical Research, Hines Hospital, Veteran Affairs Medical Center, Hines, Illinois, USA. bspring@northwestern.edu
authors.forename: Bonnie
authors.initials: B
authors.lastname: Spring
authors.forename: Brian
authors.initials: B
authors.lastname: Hitsman
authors.forename: Regina
authors.initials: R
authors.lastname: Pingitore
authors.forename: Dennis E
authors.initials: DE
authors.lastname: McChargue
authors.forename: Dianna
authors.initials: D
authors.lastname: Gunnarsdottir
authors.forename: Joyce
authors.initials: J
authors.lastname: Corsica
authors.forename: Michele
authors.initials: M
authors.lastname: Pergadia
authors.forename: Neal
authors.initials: N
authors.lastname: Doran
authors.forename: John W
authors.initials: JW
authors.lastname: Crayton
authors.forename: Sankar
authors.initials: S
authors.lastname: Baruah
authors.forename: Donald
authors.initials: D
authors.lastname: Hedeker
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D016022:Case-Control Studies; D003865:Major Depressive Disorder / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology / Q000523:psychology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D012907:Smoking / Q000523:psychology; D000074606:Smoking Prevention; D013997:Time Factors; D014364:Tryptophan / Q000009:adverse effects* / Q000097:blood / Q000172:deficiency*
chemical_list: D014364:Tryptophan