Neuroimaging and electrophysiological studies of the effects of acute tryptophan depletion: a systematic review of the literature
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.
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.
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.
KeywordsAcute tryptophan depletion Neuroimaging 5-HT EEG MEG fMRI PET
Acute tryptophan depletion
This study was supported by a grant of the Italian Ministry of Health to Biological Psychiatric Unit, the IRCCS-FBF, Italy, and by the European Union (six framework Program) grant for project GENDEP (contract LSHB-CT2003-503428) to J. P. and A. P.
- Allen P, Cleare AJ, Lee F, Fusar-Poli P, Tunstall N, Fu CH, Brammer M, McGuire P (2006) The effects of acute tryptophan depletion on prefrontal engagement. Psychopharmacology: submittedGoogle Scholar
- Bremmer J, Innis R, Salomon R (1997) Positron emission tomography measurement of cerebral metabolic correlates of tryptophan depletion-induced depressive relapse. Arch Gen Psychiatry 54:364–374Google Scholar
- Dierks T, Barta S, Demisch L, Schmeck K, Englert E, Kewitz A, Maurer K, Poustka F (1999) Intensity dependence of auditory evoked potentials (AEPs) as biological marker for cerebral serotonin levels: effects of tryptophan depletion in healthy subjects. Psychopharmacology (Berl) 146:101–107CrossRefGoogle Scholar
- Ekman P (1982) Emotion in the human face. Cambridge University Press, Cambridge UniversityGoogle Scholar
- McGuire P, Matsumoto K (2004) Functional neuroimaging in mental disorders. World Psychol 3:6–11Google Scholar
- Olendorf W, Szabo J (1976) Amino acid assignment to one of three blood–brain barrier amino acid carriers. Am J Physiol 230:94–98Google Scholar
- Rogers RD, Blackshaw AJ, Middleton HC, Matthews K, Hawtin K, Crowley C, Hopwood A, Wallace C, Deakin JF, Sahakian BJ, Robbins TW (1999) Tryptophan depletion impairs stimulus-reward learning while methylphenidate disrupts attentional control in healthy young adults: implications for the monoaminergic basis of impulsive behavior. Psychopharmacology (Berl) 146:482–491CrossRefGoogle Scholar
- Roiser JP, Blackwell AD, Cools R, Clark L, Rubinsztein DC, Robbins TW, Sahakian BJ (2006) Serotonin transporter polymorphism mediates vulnerability to loss of incentive motivation following acute tryptophan depletion. Neuropsychopharmacology. DOI 10.1038/sj.npp1301055
- Sheline Y, Barch D, Donnelly J (2001) Increased amygdala response to masked emotional faces in depressed subjects resolves with antidepressant treatment: a fMRI study. Psychiatry Res 83:127–138Google Scholar