Serotonin (5-HT) appears to modulate affective behaviours by providing a homeostatic threshold around which other transmitters respond. This general principle of activity should hold for other types of behaviour, including cognition, but has not been extensively examined. We hypothesized, based on past findings, that increased 5-HT would constrain prefrontally guided working memory functions that are mediated by catecholamine neurotransmitters. Healthy adults ingested amino acid compounds designed to deplete and load systemic tryptophan levels in a repeated-measures crossover design. Outcome variables included total plasma tryptophan, serum prolactin levels and self-report measures of mood, as well as measures of motor skill, attention, memory span and working memory for verbal, spatial and affective stimuli. Our findings indicate decrements in working memory for verbal and affective stimuli following tryptophan loading versus depletion, as well as subtle changes in vigilant attention and motor coordination. Implications for the aetiology and treatment of affective disorders and psychosis are discussed.
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