{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:22:12Z","timestamp":1785435732062,"version":"3.56.0"},"reference-count":41,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T00:00:00Z","timestamp":1780963200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012190","name":"Ministry of Science and Higher Education, Poland","doi-asserted-by":"publisher","award":["SKN\/SP\/629918\/2025"],"award-info":[{"award-number":["SKN\/SP\/629918\/2025"]}],"id":[{"id":"10.13039\/501100012190","id-type":"DOI","asserted-by":"publisher"}]},{"award":["SKN\/SP\/629918\/2025"],"award-info":[{"award-number":["SKN\/SP\/629918\/2025"]}],"id":[{"id":"https:\/\/ror.org\/05dwvd537","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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. \u0394BEHCT correlated positively with \u0394TP (RE), \u03945-HT (overall), and \u0394MLT (overall and RE), and negatively with \u0394SERT mRNA (NR). In RE, \u0394SERT mRNA negatively correlated with \u0394Stroop performance and positively with \u0394TMT. Acute DS disrupts the TP\u20135-HT\u2013MLT axis, with effects differing by mood response. These changes may influence cognitive outcomes after sleep loss.<\/jats:p>","DOI":"10.3390\/ijms27125209","type":"journal-article","created":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T09:46:54Z","timestamp":1780998414000},"page":"5209","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tryptophan-Serotonin-Melatonin Pathway as a Contributor to Changes in Mood and Cognitive Functions Induced by Sleep Deprivation"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2122-0304","authenticated-orcid":false,"given":"Marcin","family":"Sochal","sequence":"first","affiliation":[{"name":"Department of Sleep Medicine and Metabolic Disorders, Medical University of Lodz, 92-215 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1105-5298","authenticated-orcid":false,"given":"Aleksandra","family":"Wojtera","sequence":"additional","affiliation":[{"name":"Department of Sleep Medicine and Metabolic Disorders, Medical University of Lodz, 92-215 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Ditmer","sequence":"additional","affiliation":[{"name":"Department of Sleep Medicine and Metabolic Disorders, Medical University of Lodz, 92-215 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4430-6488","authenticated-orcid":false,"given":"Agata","family":"Gabryelska","sequence":"additional","affiliation":[{"name":"Department of Sleep Medicine and Metabolic Disorders, Medical University of Lodz, 92-215 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Tarasiuk-Zawadzka","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Medical University of Lodz, 92-215 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Szymon","family":"Turkiewicz","sequence":"additional","affiliation":[{"name":"Department of Sleep Medicine and Metabolic Disorders, Medical University of Lodz, 92-215 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6551-6804","authenticated-orcid":false,"given":"Filip Franciszek","family":"Karuga","sequence":"additional","affiliation":[{"name":"Department of Sleep Medicine and Metabolic Disorders, Medical University of Lodz, 92-215 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8443-4417","authenticated-orcid":false,"given":"Jakub","family":"Fichna","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Medical University of Lodz, 92-215 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Bia\u0142asiewicz","sequence":"additional","affiliation":[{"name":"Department of Sleep Medicine and Metabolic Disorders, Medical University of Lodz, 92-215 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.pcad.2023.02.005","article-title":"Sleep Physiology, Pathophysiology, and Sleep Hygiene","volume":"77","author":"Baranwal","year":"2023","journal-title":"Prog. Cardiovasc. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Sochal, M., Ditmer, M., Bia\u0142asiewicz, P., Turkiewicz, S., Karuga, F.F., and Gabryelska, A. (2023). Evaluation of Cognitive and Psychomotor Faculties in Relation to Mood-Related Symptoms under the Conditions of Sleep Deprivation. Front. Psychiatry, 14, Correction in Front. Psychiatry 2025, 16, 1627775. https:\/\/doi.org\/10.3389\/fpsyt.2025.1627775.","DOI":"10.3389\/fpsyt.2025.1627775"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.sleep.2020.07.048","article-title":"Sleep Deprivation and Its Association with Diseases\u2014A Review","volume":"77","author":"Liew","year":"2021","journal-title":"Sleep Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"113239","DOI":"10.1016\/j.psychres.2020.113239","article-title":"Clarifying the Role of Sleep in Depression: A Narrative Review","volume":"291","author":"Monti","year":"2020","journal-title":"Psychiatry Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e1020","DOI":"10.4088\/JCP.16r11332","article-title":"Meta-Analysis of the Antidepressant Effects of Acute Sleep Deprivation","volume":"78","author":"Boland","year":"2017","journal-title":"J. Clin. Psychiatry"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1111\/acps.13253","article-title":"Sleep Deprivation as Treatment for Depression: Systematic Review and Meta-Analysis","volume":"143","author":"Ioannou","year":"2021","journal-title":"Acta Psychiatr. Scand."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/B978-0-12-396971-2.00007-5","article-title":"Circadian Rhythms, Sleep Deprivation, and Human Performance","volume":"Volume 119","author":"Goel","year":"2013","journal-title":"Progress in Molecular Biology and Translational Science"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/B978-0-444-53702-7.00007-5","article-title":"Effects of Sleep Deprivation on Cognition","volume":"Volume 185","author":"Killgore","year":"2010","journal-title":"Progress in Brain Research"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1007\/s11910-023-01309-8","article-title":"Sleep Duration and Executive Function in Adults","volume":"23","author":"Sen","year":"2023","journal-title":"Curr. Neurol. Neurosci. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Davidson, M., Rashidi, N., Nurgali, K., and Apostolopoulos, V. (2022). The Role of Tryptophan Metabolites in Neuropsychiatric Disorders. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23179968"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Roth, W., Zadeh, K., Vekariya, R., Ge, Y., and Mohamadzadeh, M. (2021). Tryptophan Metabolism and Gut-Brain Homeostasis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22062973"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1111\/pcn.12944","article-title":"Peripheral Tryptophan, Serotonin, Kynurenine, and Their Metabolites in Major Depression: A Case-Control Study","volume":"74","author":"Colle","year":"2020","journal-title":"Psychiatry Clin. Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.bbr.2014.07.027","article-title":"Serotonin, Tryptophan Metabolism and the Brain-Gut-Microbiome Axis","volume":"277","author":"Clarke","year":"2015","journal-title":"Behav. Brain Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.phrs.2018.06.015","article-title":"Beyond a Neurotransmitter: The Role of Serotonin in Inflammation and Immunity","volume":"140","author":"Wu","year":"2019","journal-title":"Pharmacol. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/j.tjog.2014.10.007","article-title":"Sleep Deprivation Enhances Peripheral Serotonin Secretion to Regulate the Large Follicle Steroidogenesis of Rats","volume":"54","author":"Yang","year":"2015","journal-title":"Taiwan. J. Obstet. Gynecol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"10761","DOI":"10.1073\/pnas.1402663111","article-title":"Effect of Sleep Deprivation on the Human Metabolome","volume":"111","author":"Davies","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1001\/archpsyc.55.2.167","article-title":"Effects of Tryptophan Depletion in Drug-Free Depressed Patients Who Responded to Total Sleep Deprivation","volume":"55","author":"Neumeister","year":"1998","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1382","DOI":"10.2174\/0929867311320110003","article-title":"Platelet SERT as a Peripheral Biomarker of Serotonergic Neurotransmission in the Central Nervous System","volume":"20","author":"Robledo","year":"2013","journal-title":"Curr. Med. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.pnpbp.2004.11.015","article-title":"Distinct Effects of Sleep Deprivation on Binding to Norepinephrine and Serotonin Transporters in Rat Brain","volume":"29","author":"Moreira","year":"2005","journal-title":"Prog. Neuro-Psychopharmacol. Biol. Psychiatry"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.neulet.2005.06.048","article-title":"Serotonin Transporter MRNA Expression in Peripheral Leukocytes of Patients with Major Depression before and after Treatment with Paroxetine","volume":"389","author":"Iga","year":"2005","journal-title":"Neurosci. Lett."},{"key":"ref_21","first-page":"1000151","article-title":"Melatonin, the Hormone of Darkness: From Sleep Promotion to Ebola Treatment","volume":"4","author":"Masters","year":"2014","journal-title":"Brain Disord. Ther."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1016\/j.sleep.2020.09.018","article-title":"Association between Night-Shift Work and Level of Melatonin: Systematic Review and Meta-Analysis","volume":"75","author":"Wei","year":"2020","journal-title":"Sleep Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3090","DOI":"10.1210\/jc.2015-1859","article-title":"Physiological Levels of Melatonin Relate to Cognitive Function and Depressive Symptoms: The HEIJO-KYO Cohort","volume":"100","author":"Obayashi","year":"2015","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Tonon, A.C., Pilz, L.K., Markus, R.P., Hidalgo, M.P., and Elisabetsky, E. (2021). Melatonin and Depression: A Translational Perspective From Animal Models to Clinical Studies. Front. Psychiatry, 12.","DOI":"10.3389\/fpsyt.2021.638981"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"100204","DOI":"10.1016\/j.ynstr.2019.100204","article-title":"Acute Sleep Deprivation during Pregnancy in Rats: Rapid Elevation of Placental and Fetal Inflammation and Kynurenic Acid","volume":"12","author":"Baratta","year":"2020","journal-title":"Neurobiol. Stress"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Metri, N.J., Butt, A.S., Murali, A., Steiner-Lim, G.Z., and Lim, C.K. (2023). Normative Data on Serum and Plasma Tryptophan and Kynurenine Concentrations from 8089 Individuals Across 120 Studies: A Systematic Review and Meta-Analysis. Int. J. Tryptophan Res., 16.","DOI":"10.1177\/11786469231211184"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1093\/infdis\/jiac287","article-title":"The IDOze Study: The Link between Sleep Disruption and Tryptophan-Kynurenine Pathway Activation in Women with Human Immunodeficiency Virus","volume":"226","author":"Rogando","year":"2022","journal-title":"J. Infect. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/S0306-4522(03)00335-X","article-title":"Total Sleep Deprivation Increases Extracellular Serotonin in the Rat Hippocampus","volume":"121","author":"Wilson","year":"2003","journal-title":"Neuroscience"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1080\/10253890701754068","article-title":"A Link between Stress and Depression: Shifts in the Balance between the Kynurenine and Serotonin Pathways of Tryptophan Metabolism and the Etiology and Pathophysiology of Depression","volume":"11","author":"Miura","year":"2008","journal-title":"Stress"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"901","DOI":"10.3109\/07420528.2013.784773","article-title":"Effect of Sleep Deprivation on Rhythms of Clock Gene Expression and Melatonin in Humans","volume":"30","author":"Ackermann","year":"2013","journal-title":"Chronobiol. Int."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Sochal, M., Ditmer, M., Tarasiuk-Zawadzka, A., Binienda, A., Turkiewicz, S., Wysoki\u0144ski, A., Karuga, F.F., Bia\u0142asiewicz, P., Fichna, J., and Gabryelska, A. (2024). Circadian Rhythm Genes and Their Association with Sleep and Sleep Restriction. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms251910445"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1111\/acer.13400","article-title":"The Validity of the Montgomery\u2013Asberg Depression Rating Scale in an Inpatient Sample with Alcohol Dependence","volume":"41","author":"Hobden","year":"2017","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_33","first-page":"553","article-title":"Sleep Deprivation: Impact on Cognitive Performance","volume":"3","author":"Alhola","year":"2007","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.neuropsychologia.2018.03.032","article-title":"Sleep Deprivation Increases the Costs of Attentional Effort: Performance, Preference and Pupil Size","volume":"123","author":"Massar","year":"2019","journal-title":"Neuropsychologia"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"A34","DOI":"10.1093\/sleep\/zsad077.0075","article-title":"Melatonin Impairs Morning Cognition in Healthy Young Adults without Any Benefit to Sleep","volume":"46","author":"Wernette","year":"2023","journal-title":"Sleep"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"6214","DOI":"10.1523\/JNEUROSCI.3781-16.2017","article-title":"Chronic-Stress-Induced Behavioral Changes Associated with Subregion-Selective Serotonin Cell Death in the Dorsal Raphe","volume":"37","author":"Natarajan","year":"2017","journal-title":"J. Neurosci."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Tseilikman, V.E., Tseilikman, O.B., Karpenko, M.N., Traktirov, D.S., Obukhova, D.A., Shatilov, V.A., Zhukov, M.S., Manuilov, G.V., Yegorov, O.N., and Aristov, M.R. (2024). Unraveling the Serotonergic Mechanism of Stress-Related Anxiety: Focus on Co-Treatment with Resveratrol and Selective Serotonin Reuptake Inhibitors. Biomedicines, 12.","DOI":"10.3390\/biomedicines12112455"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"233","DOI":"10.5665\/sleep.4404","article-title":"How Acute Total Sleep Loss Affects the Attending Brain: A Meta-Analysis of Neuroimaging Studies","volume":"38","author":"Ma","year":"2015","journal-title":"Sleep"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Yao, L., Wang, Y., Gao, Y., Gao, H., and Guo, X. (2023). The Role of the Fronto-Parietal Network in Modulating Sustained Attention under Sleep Deprivation: An Functional Magnetic Resonance Imaging Study. Front. Psychiatry, 14.","DOI":"10.3389\/fpsyt.2023.1289300"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.jad.2016.12.041","article-title":"What does the MADRS mean? Equipercentile linking with the CGI using a company database of mirtazapine studies","volume":"210","author":"Leucht","year":"2017","journal-title":"J. Affect. Disord."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.jad.2006.11.020","article-title":"Polysomnography and criteria for the antidepressant response to sleep deprivation","volume":"101","author":"Clark","year":"2007","journal-title":"J. Affect. Disord."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/12\/5209\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T10:07:44Z","timestamp":1780999664000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/12\/5209"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,9]]},"references-count":41,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["ijms27125209"],"URL":"https:\/\/doi.org\/10.3390\/ijms27125209","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,9]]}}}