Effect of Tryptophan Depletion on Smokers and Nonsmokers With and Without History of Major Depression

Bonnie Spring, Brian Hitsman, Regina Pingitore, Dennis E. McChargue, Dianna Gunnarsdottir, Joyce Corsica, Michele Pergadia, Neal Doran, John W. Crayton, Sankar Baruah, Donald Hedeker

Research output: Contribution to journalArticle

15 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)70-77
Number of pages8
JournalBiological Psychiatry
Issue number1
Publication statusPublished - Jan 1 2007



  • Serotonin
  • cigarette smoking
  • major depression
  • nicotine dependence
  • tryptophan depletion
  • vulnerability

ASJC Scopus subject areas

  • Biological Psychiatry

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