Neuroimaging and electrophysiological studies of the effects of acute tryptophan depletion: a systematic review of the literature

RATIONALE: There is a growing psychopharmacological literature on the use of Acute Tryptophan Depletion (ATD) for experimental modulation of the serotonergic system. To date, no systematic review has been undertaken assessing the neurophysiological effects following this acute central 5-HT manipulation. MATERIALS AND METHODS: A comprehensive MEDLINE, EMBASE, PsycINFO search was performed for reports on neural substrates of Acute Tryptophan Depletion in healthy individuals and in clinical population. RESULTS: Twenty-eight placebo-controlled studies were included in the review. Although tryptophan depletion reduced plasma serotonin levels in all studies, significant effects on mood were only observed in studies with recovered depressed patients. In functional neuroimaging studies ATD was consistently found to modulate cortical activity in prefrontal areas implicated in mnemonic and executive functions and in orbitofrontal, cingulate, and subcortical regions associated with emotional processing. Electrophysiological studies indicated that ATD has a significant effect on both "selective" and "involuntary" attention. CONCLUSIONS: The combination of ATD with modern brain imaging techniques allows the investigation of the neurophysiological effects of reduced 5-HT synthesis on global brain activity, executive functions, memory, attention, and affect.