title: Effect of acute tryptophan depletion on pre-frontal engagement.
abstract: BACKGROUND
  Serotonin is known to modulate cognitive functioning and has been implicated in the cognitive deficits associated with affective disorders. The present study examined regional brain activation during two tasks that are known to engage the pre-frontal cortex and are performed poorly by patients with depression and bipolar disorder. We tested the hypothesis that acute tryptophan depletion (ATD) would attenuate pre-frontal activation during both tasks.
  
  
  METHODS
  Ten healthy right-handed volunteers were studied using functional MRI whilst performing a 2-back verbal working memory task and a phonological verbal fluency task. Subjects were studied in two separate sessions, after either a tryptophan-free or a balanced amino acid drink, in a double-blind design. Task performance and mood were measured online.
  
  
  RESULTS
  Relative to sham depletion, ATD attenuated activation in the right superior frontal gyrus during the 2-back task and in the medial frontal gyrus and precuneus during the verbal fluency task. ATD lowered total plasma tryptophan by 79% but had no significant effect on either task performance or mood.
  
  
  CONCLUSIONS
  The engagement of pre-frontal cortex during verbal working memory and verbal fluency tasks is significantly modulated by central serotonergic activity. The different location of these modulatory effects within the frontal cortex may reflect the engagement of distinct cognitive processes by the respective tasks.
authors.affiliation: Division of Psychological Medicine P067, Institute of Psychiatry, De Crespigny Park, London, UK. p.allen@iop.kcl.ac.uk
authors.forename: Paul P
authors.initials: PP
authors.lastname: Allen
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Cleare
authors.forename: Francis
authors.initials: F
authors.lastname: Lee
authors.forename: Paolo
authors.initials: P
authors.lastname: Fusar-Poli
authors.forename: Nigel
authors.initials: N
authors.lastname: Tunstall
authors.forename: Cynthia H Y
authors.initials: CH
authors.lastname: Fu
authors.forename: Micheal J
authors.initials: MJ
authors.lastname: Brammer
authors.forename: Philip K
authors.initials: PK
authors.lastname: McGuire
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000339:Affect; D000374:Aggression; D000596:Amino Acids / Q000008:administration & dosage; D001931:Brain Mapping; D003071:Cognition; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008568:Memory; D017397:Prefrontal Cortex / Q000502:physiology*; D011569:Psychiatric Status Rating Scales; D012016:Reference Values; D014364:Tryptophan / Q000097:blood / Q000172:deficiency*; D014705:Verbal Behavior
chemical_list: D000596:Amino Acids; D014364:Tryptophan