, Volume 188, Issue 2, pp 131–143 | Cite as

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

  • Paolo Fusar-PoliEmail author
  • Paul Allen
  • Philip McGuire
  • Anna Placentino
  • Mariachiara Cortesi
  • Jorge Perez



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.


Acute 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.


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Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Paolo Fusar-Poli
    • 1
    • 2
    Email author
  • Paul Allen
    • 2
  • Philip McGuire
    • 2
  • Anna Placentino
    • 3
  • Mariachiara Cortesi
    • 4
  • Jorge Perez
    • 3
  1. 1.Department of Applied and Psychobehavioral Health SciencesUniversity of PaviaPaviaItaly
  2. 2.Institute of Psychiatry, Department of Psychological MedicineKing’s CollegeLondonUK
  3. 3.Unit of Biological PsychiatryIRCCS Fatebenefratelli “San Giovanni di Dio”BresciaItaly
  4. 4.Department of Child Neurology and PsychiatryUniversity of PaviaPaviaItaly

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