Both low mood and cognitive impairment are associated with poor psychosocial functioning. Therefore, we argue that remediation of cognitive impairment and alleviation of depressive symptoms each play an important role in improving outcome for patients with depression. In conclusion, this systematic review and meta-analysis demonstrates that cognitive impairment represents a core feature of depression that cannot be considered an epiphenomenon that is entirely secondary to symptoms of low mood and that may be a valuable target for future interventions.

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Animal and human studies have provided evidence for serotonergic modulation of cognitive processes. However, the exact nature of this relationship is not clear. We used the acute tryptophan depletion (ATD) method to investigate the effects of lowered serotonin synthesis on cognitive functions in 17 healthy young volunteers. The study was conducted according to a placebo-controlled, double-blind, crossover design. Cognitive performance and mood were assessed at baseline and 5 and 9 h after administration of ATD. A specific impairment of word recognition, without effects on short-term memory, occurred during ATD. No memory deficits were seen if ATD was induced after acquisition of new words. The Stroop Test and dichotic listening task demonstrated a modality independent improvement of focussed attention after ATD. Fluency was also improved after ATD. ATD did not alter speed of information processing, divided attention or planning functions. These results indicate that serotonin is essential in the process of long-term memory consolidation, primarily in the first 30 min after acquisition. Improvement of specific cognitive processes by lowered 5-HT function may be linked to the removal of inhibitory actions of 5-HT in the cortex.

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.