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

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.