Tryptophan-Serotonin-Melatonin Pathway as a Contributor to Changes in Mood and Cognitive Functions Induced by Sleep Deprivation

Sleep deprivation (DS) is a reduction in sleep duration due to voluntary or external factors. The mechanisms underlying the psychological and cognitive consequences of DS are complex and incompletely understood; one proposed pathway involves alterations in the serotonin (5-HT) and melatonin (MLT) systems. This study aimed to assess the effects of a single night of DS on the tryptophan (TP)-5-HT-MLT system and to examine their associations with mood and cognitive performance. Eighty healthy adults underwent polysomnography (PSG) and actigraphy-monitored DS. Blood samples, mood assessments, and cognitive tests (BEHCT, TMT, Stroop) were performed before and after PSG and DS. Levels of serotonin transporter (SERT) mRNA, TP, 5-HT, and MLT were measured. Participants were classified as Responders (RE) or Non-Responders (NR) based on post-DS mood change. DS significantly decreased TP and MLT overall. In NR, 5-HT increased and MLT decreased, unlike in RE. ΔBEHCT correlated positively with ΔTP (RE), Δ5-HT (overall), and ΔMLT (overall and RE), and negatively with ΔSERT mRNA (NR). In RE, ΔSERT mRNA negatively correlated with ΔStroop performance and positively with ΔTMT. Acute DS disrupts the TP–5-HT–MLT axis, with effects differing by mood response. These changes may influence cognitive outcomes after sleep loss.