Double-blind trial of the effects of tryptophan depletion on depression and cerebral blood flow in smokers

Michele Pergadia*, Bonnie Spring, Lukasz M. Konopka, Barbara Twardowska, Parvez Shirazi, John W. Crayton

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Studies of clinically depressed patients have documented left frontal lobe hypoactivity. Smokers also show an increased prevalence of depression and evidence that nicotine normalizes qEEG indices of left frontal lobe activity. Tryptophan depletion (TD) has been shown to increase negative mood in smokers, particularly those with recurrent depression. Thus, in smokers, we expected that increased depression during TD would be associated with decreased cerebral blood flow, specifically in the left frontal lobe. Hamilton depression scores and relative regional cerebral blood flow (rCBF) were measured with SPECT using 99mTc-hexamethylpropyleneamineoxime in seven smokers after TD and after a control procedure. Decreased bilateral cerebral blood flow to the inferior frontal (IF) lobe following TD relative to placebo was associated with increased depressed mood (r=-.653, P<.05). Among smokers, a decrease in brain serotonin is associated with increased depressed mood and with focal bilateral decreases in IF activity. Chronic nicotine exposure appears to be associated with cortical responses suggestive of depressive vulnerability.

Original languageEnglish (US)
Pages (from-to)665-671
Number of pages7
JournalAddictive Behaviors
Issue number4
StatePublished - Jun 2004


  • Depression
  • Inferior frontal cortex
  • Smoking
  • Tryptophan depletion

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Clinical Psychology
  • Medicine (miscellaneous)
  • Toxicology


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