Effects of acute tryptophan depletion on executive function in healthy male volunteers.
BACKGROUND
Neurocognitive impairment is frequently described in a number of psychiatric disorders and may be a direct consequence of serotonergic dysfunction. As impairments in executive functions are some of the most frequently described, the purpose of this study was to examine the performance of normal volunteers on a range of executive tasks following a transient reduction of central serotonin (5-HT) levels using the method of acute tryptophan depletion (ATD).


METHODS
Fifteen healthy male subjects participated in a within-subject, double-blind, counterbalanced crossover study. ATD was induced by ingestion of a 100 g amino-acid drink. Executive function was evaluated using the Wisconsin Card Sorting Test, Stroop, Verbal Fluency and Trail Making. Visual analogue scales were administered to assess mood.


RESULTS
Plasma free and total tryptophan concentrations were significantly reduced by the depleting drink (P < 0.001). ATD selectively improved motor speed/ attention on the Trails A test (P = 0.027), with no effect on subjective ratings of mood. Interaction effects between drink and the order of drink administration were observed on most neurocognitive tests.


CONCLUSIONS
The improvement in simple motor speed/ attention following ATD is in keeping with the ascribed role of 5-HT in the cortex, however performance on tests of executive function is not robustly altered. The presence of interaction effects on most tasks suggests that subtle changes may occur but are masked, possibly by simple learning effects, in the context of a crossover design. This has implications for the design of future studies, particularly those examining executive functions.
Gallagher
Peter
P
Stanley Research Centre, School of Neurology, Neurobiology and Psychiatry, University of Newcastle upon Tyne, NE1 4LP, UK. peter.gallagher@ncl.ac.uk
Massey
Anna E
AE
Young
Allan H
AH
McAllister-Williams
R Hamish
RH
D000293:Adolescent; D000328:Adult; D001288:Attention / Q000502:physiology; D003072:Cognition Disorders / Q000175:diagnosis / Q000503:physiopathology* / Q000523:psychology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005625:Frontal Lobe / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D011597:Psychomotor Performance / Q000502:physiology; D011930:Reaction Time / Q000502:physiology; D012701:Serotonin / Q000096:biosynthesis / Q000502:physiology*; D012737:Sex Factors; D014145:Trail Making Test; D014364:Tryptophan / Q000097:blood / Q000172:deficiency* / Q000378:metabolism
D012701:Serotonin; D014364:Tryptophan