TRYPTOPHAN DEPLETION IN NORMAL VOLUNTEERS PRODUCES SELECTIVE IMPAIRMENTS IN LEARNING AND MEMORY

The amino-acid L-tryptophan is essential in the synthesis of brain ser otonin, and its depletion can lead to a widespread reduction in centra l serotonergic activity. A placebo-controlled cross-over within-subjec ts design (n = 12) examined the effects of tryptophan depletion on hum an cognitive performance. A low-tryptophan (low-TRP) drink successfull y reduced the levels of plasma and total free tryptophan. Computerized tests of memory, learning and executive function revealed selective a nd non-sedative impairments on cognitive performance following the act ive drink. Specifically, low-TRP impaired learning as seen in tests of visual discrimination and paired associates. Furthermore, low-TRP len gthened thinking times during the Tower of London planning task, but o nly in subjects already familiar with the task, suggesting a retrieval deficit. No evidence was found for an effect of the low-TRP drink on measures sensitive to frontal lobe dysfunction, supporting instead a s pecific role for the serotonergic system in the processes of memory an d learning not directly implicated in frontal lobe function.