Tryptophan depletion in normal volunteers produces selective impairment in memory consolidation

Abstract

Serotonin (5-hydroxytryptamine; 5-HT) circuits may play a role in cognitive performance, particularly in learning and memory. Cognitive impairment is often seen in depressed patients, in whom 5-HT turnover in the brain is thought to be lowered. A possible human pharmacological model to study the involvement of the serotonergic system in cognitive impairment is to reduce central 5-HT synthesis through L-tryptophan depletion in healthy subjects. In this study, the cognitive effects of tryptophan depletion were assessed and whether genetically or developmentally determined vulnerability factors were predictive of the cognitive impairment induced by tryptophan depletion. Sixteen healthy volunteers with a positive family history of depression and 11 without were given 100 g of an amino acid mixture with or without tryptophan, according to a double-blind, cross-over design. Tryptophan depletion specifically impaired long-term memory performance in all subjects: delayed recall performance, recognition sensitivity, and recognition reaction times were significantly impaired after tryptophan depletion relative to placebo. Short-term memory and perceptual and psychomotor functions were unchanged. There were no differences between groups with a positive and a negative family history for depression. On the basis of these results, it is concluded that tryptophan depletion specifically impairs long-term memory formation, presumably as a result of an acute decrease in 5-HT turnover in the brain.

Pronounced Cognitive Deficits Following an Intravenous L-Tryptophan Challenge in First-Degree Relatives of Bipolar Patients Compared to Healthy Controls

“…Deficits in STM have also been described following acute 5-HT challenges with ipsapirone (Riedel et al, 2002) and fenfluramine (Luciana et al, 1998) in healthy subjects. The detrimental effects of Trp on memory were comparative with those described following ATD (Sobczak et al, 2002c;Riedel et al, 1999;Schmitt et al, 2000;Rubinsztein et al, 2001). The fact that both an increase and decrease in Trp results in memory dysfunctions may suggest that there is an optimal 5-HT level for cognitive performance.…”

“…Serotonin (5-hydroxytryptophan; 5-HT) has been implicated in psychopathology of BD and has also been associated with cognitive performance, particularly learning and memory (Young et al, 1994;Riedel et al, 1999;Schmitt et al, 2000). Changes in cognitive performance following selective 5-HT modulations are important biological markers for brain 5-HT responsivity (Riedel et al, 2002).…”

Dissociable Hormonal, Cognitive and Mood Responses to Neuroendocrine Challenge Evidence for Receptor-Specific Serotonergic Dysregulation in Depressed Mood

“…This mechanism may account for positive effects of 5-HT in patients and may also explain tryptophan-depletion induced memory consolidation impairment and mood lowering in normal subjects (Riedel et al 1999).…”

The Selective 5-HT6 Receptor Antagonist Ro4368554 Restores Memory Performance in Cholinergic and Serotonergic Models of Memory Deficiency in the Rat

“…Dysfunctional memory occurred after acute lowering in plasma tryptophan (TRP; precursor of 5-HT) levels . The cognitive impairments after TRP depletion were found in healthy volunteers (Park et al, 1994;Riedel et al, 1999;Rubinsztein et al, 2001), as well as in patients with neurological disorders such as Alzheimer disease , bipolar disorders (Sobczak et al, 2002) or schizophrenia (Golightly et al, 2001).…”