{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T12:23:36Z","timestamp":1784982216365,"version":"3.55.0"},"reference-count":80,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,11,2]],"date-time":"2023-11-02T00:00:00Z","timestamp":1698883200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,11,2]],"date-time":"2023-11-02T00:00:00Z","timestamp":1698883200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>After Covid-19 infection, 12.5% develops post-Covid-syndrome (PCS). Symptoms indicate numerous affected organ systems. After a year, chronic fatigue, dysautonomia and neurological and neuropsychiatric complaints predominate. In this study, 95 PCS patients were treated with selective serotonin reuptake inhibitors (SSRIs). This study used an exploratory questionnaire and found that two-thirds of patients had a reasonably good to strong response on SSRIs, over a quarter of patients had moderate response, while 10% reported no response. Overall, patients experienced substantial improved well-being. Brainfog and sensory overload decreased most, followed by chronic fatigue and dysautonomia. Outcomes were measured with three different measures that correlated strongly with each other. The response to SSRIs in PCS conditions was explained by seven possible neurobiological mechanisms based on recent literature on PCS integrated with already existing knowledge. Important for understanding these mechanisms is the underlying biochemical interaction between various neurotransmitter systems and parts of the immune system, and their dysregulation in PCS. The main link appears to be with the metabolic kynurenine pathway (KP) which interacts extensively with the immune system. The KP uses the same precursor as serotonin: tryptophan. The KP is overactive in PCS which maintains inflammation and which causes a lack of tryptophan. Finally, potential avenues for future research to advance this line of clinical research are discussed.<\/jats:p>","DOI":"10.1038\/s41598-023-45072-9","type":"journal-article","created":{"date-parts":[[2023,11,2]],"date-time":"2023-11-02T07:02:06Z","timestamp":1698908526000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Treatment of 95 post-Covid patients with SSRIs"],"prefix":"10.1038","volume":"13","author":[{"given":"Carla P.","family":"Rus","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bert E. K.","family":"de Vries","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingmar E. J.","family":"de Vries","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Idelette","family":"Nutma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. J. Sandra","family":"Kooij","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,11,2]]},"reference":[{"key":"45072_CR1","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1038\/s41579-022-00846-2","volume":"21","author":"HE Davis","year":"2023","unstructured":"Davis, H. E., McCorkell, L., Vogel, J. M. & Topol, E. J. Long COVID: Major findings, mechanisms and recommendations. Nat. Rev. Microbiol. 21, 133\u2013146 (2023).","journal-title":"Nat. Rev. Microbiol."},{"key":"45072_CR2","unstructured":"Office for National Statistics. Prevalence of ongoing symptoms following coronavirus (COVID-19) infection in the UK: 30 March 2023. https:\/\/www.ons.gov.uk\/peoplepopulationandcommunity\/healthandsocialcare\/conditionsanddiseases\/bulletins\/prevalenceofongoingsymptomsfollowingcoronaviruscovid19infectionintheuk\/30march2023 (2023)."},{"key":"45072_CR3","unstructured":"Bach, K. New data shows long Covid is keeping as many as 4 million people out of work. https:\/\/www.brookings.edu\/articles\/new-data-shows-long-covid-is-keeping-as-many-as-4-million-people-out-of-work\/."},{"key":"45072_CR4","unstructured":"Fogoros, R. N. What Is Tilt Table Testing? What to expect when undergoing this test. https:\/\/www.verywellhealth.com\/tilt-table-testing-1745418 (2022)."},{"key":"45072_CR5","doi-asserted-by":"publisher","first-page":"e1146","DOI":"10.1212\/NXI.0000000000001146","volume":"9","author":"AL Oaklander","year":"2022","unstructured":"Oaklander, A. L. et al. Peripheral neuropathy evaluations of patients with prolonged long COVID. Neurol. Neuroimmunol. Neuroinflamm. 9, e1146 (2022).","journal-title":"Neurol. Neuroimmunol. Neuroinflamm."},{"key":"45072_CR6","doi-asserted-by":"publisher","first-page":"922422","DOI":"10.3389\/fcimb.2022.922422","volume":"12","author":"MAF Queiroz","year":"2022","unstructured":"Queiroz, M. A. F. et al. Cytokine profiles associated with acute COVID-19 and long COVID-19 syndrome. Front Cell Infect. Microbiol. 12, 922422 (2022).","journal-title":"Front Cell Infect. Microbiol."},{"issue":"375","key":"45072_CR7","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1126\/science.abm2052","volume":"1979","author":"S Spudich","year":"2022","unstructured":"Spudich, S. & Nath, A. Nervous system consequences of COVID-19. Science 1979(375), 267\u2013269 (2022).","journal-title":"Science"},{"key":"45072_CR8","doi-asserted-by":"publisher","first-page":"3484","DOI":"10.1016\/j.neuron.2022.10.006","volume":"110","author":"M Monje","year":"2022","unstructured":"Monje, M. & Iwasaki, A. The neurobiology of long COVID. Neuron 110, 3484\u20133496 (2022).","journal-title":"Neuron"},{"key":"45072_CR9","doi-asserted-by":"publisher","first-page":"e2513","DOI":"10.1002\/brb3.2513","volume":"12","author":"J Hugon","year":"2022","unstructured":"Hugon, J. et al. Cognitive decline and brainstem hypometabolism in long COVID: A case series. Brain Behav. 12, e2513 (2022).","journal-title":"Brain Behav."},{"key":"45072_CR10","first-page":"996","volume-title":"Principels Of Neural Sciences","author":"CB Saper","year":"2020","unstructured":"Saper, C. B. & Elmquist, J. K. The brain stem. In Principels Of Neural Sciences (eds Kandel, E. R. et al.) 996\u2013999 (The McGraw-Hill Companies, 2020)."},{"key":"45072_CR11","doi-asserted-by":"publisher","first-page":"5104","DOI":"10.1038\/s41467-022-32507-6","volume":"13","author":"C Kedor","year":"2022","unstructured":"Kedor, C. et al. A prospective observational study of post-COVID-19 chronic fatigue syndrome following the first pandemic wave in Germany and biomarkers associated with symptom severity. Nat. Commun. 13, 5104 (2022).","journal-title":"Nat. Commun."},{"key":"45072_CR12","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1038\/mp.2015.29","volume":"21","author":"M Hornig","year":"2016","unstructured":"Hornig, M. et al. Cytokine network analysis of cerebrospinal fluid in myalgic encephalomyelitis\/chronic fatigue syndrome. Mol. Psychiatry 21, 261\u2013269 (2016).","journal-title":"Mol. Psychiatry"},{"key":"45072_CR13","doi-asserted-by":"publisher","first-page":"6806","DOI":"10.1007\/s12035-016-0170-2","volume":"54","author":"G Morris","year":"2017","unstructured":"Morris, G., Anderson, G. & Maes, M. Hypothalamic-pituitary-adrenal hypofunction in myalgic encephalomyelitis (ME)\/chronic fatigue syndrome (CFS) as a consequence of activated immune-inflammatory and oxidative and nitrosative pathways. Mol. Neurobiol. 54, 6806\u20136819 (2017).","journal-title":"Mol. Neurobiol."},{"key":"45072_CR14","volume-title":"Principles of Neural Science","author":"B Lowell","year":"2020","unstructured":"Lowell, B., Swanson, L. & Hro, J. The hypothalamus: Autonomic, hormonal, and behavioral control of survival. In Principles of Neural Science (eds Kandel, E. et al.) (The McGraw-Hill Company, London, 2020)."},{"key":"45072_CR15","volume-title":"Pharmacological Aspects of Corticotrophinergic and Vasopressinergic Function Test for HPA Axis Activation","author":"GE Jacobs","year":"2010","unstructured":"Jacobs, G. E. Pharmacological Aspects of Corticotrophinergic and Vasopressinergic Function Test for HPA Axis Activation (Leiden University, 2010)."},{"key":"45072_CR16","doi-asserted-by":"publisher","unstructured":"Bao, A.-M., Ruh\u00e9, H. G., Gao, S.-F. & Swaab, D. F. Neurotransmitters and neuropeptides in depression. 107\u2013136 (2012). https:\/\/doi.org\/10.1016\/B978-0-444-52002-9.00008-5.","DOI":"10.1016\/B978-0-444-52002-9.00008-5"},{"key":"45072_CR17","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1016\/j.psyneuen.2014.10.024","volume":"52","author":"HG Ruh\u00e9","year":"2015","unstructured":"Ruh\u00e9, H. G. et al. Longitudinal effects of the SSRI paroxetine on salivary cortisol in Major depressive disorder. Psychoneuroendocrinology 52, 261\u2013271 (2015).","journal-title":"Psychoneuroendocrinology"},{"key":"45072_CR18","doi-asserted-by":"publisher","first-page":"136","DOI":"10.3389\/fimmu.2014.00136","volume":"5","author":"M-A Bellavance","year":"2014","unstructured":"Bellavance, M.-A. & Rivest, S. The HPA\u2014Immune axis and the immunomodulatory actions of glucocorticoids in the brain. Front. Immunol. 5, 136 (2014).","journal-title":"Front. Immunol."},{"key":"45072_CR19","doi-asserted-by":"publisher","unstructured":"Klein, J. et al. Distinguishing features of Long COVID identified through immune profiling. medRxiv https:\/\/doi.org\/10.1038\/s41586-023-06651-y (2023).","DOI":"10.1038\/s41586-023-06651-y"},{"key":"45072_CR20","first-page":"241","volume-title":"Principles of Neural Science","author":"S Siegelbaum","year":"2021","unstructured":"Siegelbaum, S. & Fischbach, G. Synaptic transmission. In Principles of Neural Science (eds Kandel, E. R. et al.) 241\u2013385 (McGrawHill, 2021)."},{"key":"45072_CR21","first-page":"1515","volume-title":"Principles of Neural Science","author":"S Hyman","year":"2020","unstructured":"Hyman, S. & Tamminga, C. Disorders of mood and anxiety. In Principles of Neural Science (eds Kandel, E. R. et al.) 1515 (The McGraw-Hill Company, 2020)."},{"key":"45072_CR22","doi-asserted-by":"publisher","first-page":"i81","DOI":"10.1136\/gut.51.suppl_1.i81","volume":"51","author":"M Camilleri","year":"2002","unstructured":"Camilleri, M. Serotonergic modulation of visceral sensation: Lower gut. Gut 51, i81\u2013i86 (2002).","journal-title":"Gut"},{"key":"45072_CR23","doi-asserted-by":"publisher","first-page":"682868","DOI":"10.3389\/fpsyt.2021.682868","volume":"12","author":"P Sj\u00f6stedt","year":"2021","unstructured":"Sj\u00f6stedt, P., Enander, J. & Isung, J. Serotonin reuptake inhibitors and the gut microbiome: Significance of the gut microbiome in relation to mechanism of action, treatment response, side effects, and tachyphylaxis. Front Psychiatry 12, 682868 (2021).","journal-title":"Front Psychiatry"},{"key":"45072_CR24","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1016\/j.trsl.2007.10.004","volume":"151","author":"DJ McCloskey","year":"2008","unstructured":"McCloskey, D. J. et al. Selective serotonin reuptake inhibitors: Measurement of effect on platelet function. Transl. Res. 151, 168\u2013172 (2008).","journal-title":"Transl. Res."},{"key":"45072_CR25","volume-title":"Principles of Neural Science","author":"ER Kandel","year":"2020","unstructured":"Kandel, E. R., Koester, J., Mack, S. & Siegelbaum, S. Principles of Neural Science (The McGraw-Hill Companies, 2020)."},{"key":"45072_CR26","doi-asserted-by":"publisher","first-page":"860867","DOI":"10.3389\/fimmu.2022.860867","volume":"13","author":"Y M\u00e1ndi","year":"2022","unstructured":"M\u00e1ndi, Y., Stone, T. W., Guillemin, G. J., V\u00e9csei, L. & Williams, R. O. Editorial: Multiple implications of the kynurenine pathway in inflammatory diseases: Diagnostic and therapeutic applications. Front Immunol. 13, 860867 (2022).","journal-title":"Front Immunol."},{"key":"45072_CR27","first-page":"591","volume":"19","author":"H Fanet","year":"2021","unstructured":"Fanet, H., Capuron, L., Castanon, N., Calon, F. & Vancassel, S. Tetrahydrobioterin (BH4) pathway: From metabolism to neuropsychiatry. Curr. Neuropharmacol. 19, 591\u2013609 (2021).","journal-title":"Curr. Neuropharmacol."},{"key":"45072_CR28","doi-asserted-by":"publisher","first-page":"104729","DOI":"10.1016\/j.ebiom.2023.104729","volume":"94","author":"L Guo","year":"2023","unstructured":"Guo, L. et al. Prolonged indoleamine 2,3-dioxygenase-2 activity and associated cellular stress in post-acute sequelae of SARS-CoV-2 infection. EBioMedicine 94, 104729 (2023).","journal-title":"EBioMedicine"},{"key":"45072_CR29","doi-asserted-by":"publisher","first-page":"41473","DOI":"10.1038\/srep41473","volume":"7","author":"CK Lim","year":"2017","unstructured":"Lim, C. K. et al. Kynurenine pathway metabolomics predicts and provides mechanistic insight into multiple sclerosis progression. Sci. Rep. 7, 41473 (2017).","journal-title":"Sci. Rep."},{"key":"45072_CR30","doi-asserted-by":"publisher","unstructured":"Cysique, L. A. et al. Post-acute COVID-19 cognitive impairment and decline uniquely associate with kynurenine pathway activation: A longitudinal observational study. medRxiv 2022.06.07.22276020 (2022). https:\/\/doi.org\/10.1101\/2022.06.07.22276020.","DOI":"10.1101\/2022.06.07.22276020"},{"key":"45072_CR31","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1038\/s41590-022-01396-8","volume":"24","author":"RQ Cron","year":"2023","unstructured":"Cron, R. Q. Immunologic prediction of long COVID. Nat. Immunol. 24, 207\u2013208 (2023).","journal-title":"Nat. Immunol."},{"key":"45072_CR32","doi-asserted-by":"publisher","first-page":"1332","DOI":"10.3390\/biomedicines10061332","volume":"10","author":"M Chilosi","year":"2022","unstructured":"Chilosi, M. et al. Unbalanced IDO1\/IDO2 endothelial expression and skewed keynurenine pathway in the pathogenesis of COVID-19 and Post-COVID-19 pneumonia. Biomedicines 10, 1332 (2022).","journal-title":"Biomedicines"},{"key":"45072_CR33","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1038\/s41380-021-01309-5","volume":"27","author":"J Kornhuber","year":"2022","unstructured":"Kornhuber, J., Hoertel, N. & Gulbins, E. The acid sphingomyelinase\/ceramide system in COVID-19. Mol. Psychiatry 27, 307\u2013314 (2022).","journal-title":"Mol. Psychiatry"},{"key":"45072_CR34","doi-asserted-by":"publisher","first-page":"875","DOI":"10.2174\/138161212799436476","volume":"18","author":"T Niitsu","year":"2012","unstructured":"Niitsu, T., Iyo, M. & Hashimoto, K. Sigma-1 receptor agonists as therapeutic drugs for cognitive impairment in neuropsychiatric diseases. Curr. Pharm. Des. 18, 875\u2013883 (2012).","journal-title":"Curr. Pharm. Des."},{"key":"45072_CR35","doi-asserted-by":"publisher","first-page":"3562","DOI":"10.1038\/s41380-022-01545-3","volume":"27","author":"E Khani","year":"2022","unstructured":"Khani, E. & Entezari-Maleki, T. Fluvoxamine and long COVID-19; a new role for sigma-1 receptor (S1R) agonists. Mol. Psychiatry 27, 3562\u20133562 (2022).","journal-title":"Mol. Psychiatry"},{"key":"45072_CR36","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1097\/JCP.0000000000001543","volume":"42","author":"U Bonnet","year":"2022","unstructured":"Bonnet, U. & Juckel, G. COVID-19 outcomes: Does the use of psychotropic drugs make a difference? Accumulating evidence of a beneficial effect of antidepressants\u2014A scoping review. J. Clin. Psychopharmacol. 42, 284\u2013292 (2022).","journal-title":"J. Clin. Psychopharmacol."},{"key":"45072_CR37","doi-asserted-by":"publisher","unstructured":"Sidky, H. et al. Assessing the effect of selective serotonin reuptake inhibitors in the prevention of post-acute sequelae of COVID-19. medRxiv 2022.11.09.22282142 (2023). https:\/\/doi.org\/10.1101\/2022.11.09.22282142.","DOI":"10.1101\/2022.11.09.22282142"},{"key":"45072_CR38","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.euroneuro.2021.09.009","volume":"54","author":"MG Mazza","year":"2022","unstructured":"Mazza, M. G., Zanardi, R., Palladini, M., Rovere-Querini, P. & Benedetti, F. Rapid response to selective serotonin reuptake inhibitors in post-COVID depression. Eur. Neuropsychopharmacol. 54, 1\u20136 (2022).","journal-title":"Eur. Neuropsychopharmacol."},{"key":"45072_CR39","doi-asserted-by":"publisher","first-page":"1220","DOI":"10.3126\/nje.v12i3.48532","volume":"12","author":"I Banerjee","year":"2022","unstructured":"Banerjee, I., Robinson, J. & Sathian, B. Treatment of Long COVID or Post COVID syndrome: A pharmacological approach. Nepal J. Epidemiol. 12, 1220\u20131223 (2022).","journal-title":"Nepal J. Epidemiol."},{"key":"45072_CR40","doi-asserted-by":"publisher","first-page":"6564","DOI":"10.1523\/JNEUROSCI.2618-20.2021","volume":"41","author":"M Hersey","year":"2021","unstructured":"Hersey, M. et al. Inflammation-induced histamine impairs the capacity of escitalopram to increase hippocampal extracellular serotonin. J. Neurosci. 41, 6564\u20136577 (2021).","journal-title":"J. Neurosci."},{"key":"45072_CR41","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgad207","author":"L di Filippo","year":"2023","unstructured":"di Filippo, L. et al. Low vitamin D levels are associated with long COVID syndrome in COVID-19 survivors. J. Clin. Endocrinol. Metab. https:\/\/doi.org\/10.1210\/clinem\/dgad207 (2023).","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"45072_CR42","doi-asserted-by":"publisher","first-page":"1625","DOI":"10.3390\/nu14081625","volume":"14","author":"L Barrea","year":"2022","unstructured":"Barrea, L. et al. Vitamin D: A role also in long COVID-19?. Nutrients 14, 1625 (2022).","journal-title":"Nutrients"},{"key":"45072_CR43","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1093\/nutrit\/nuab092","volume":"80","author":"KS Batista","year":"2022","unstructured":"Batista, K. S. et al. The role of vitamin B12 in viral infections: A comprehensive review of its relationship with the muscle\u2013gut\u2013brain axis and implications for SARS-CoV-2 infection. Nutr. Rev. 80, 561\u2013578 (2022).","journal-title":"Nutr. Rev."},{"key":"45072_CR44","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.jpsychores.2009.10.007","volume":"69","author":"M Cella","year":"2010","unstructured":"Cella, M. & Chalder, T. Measuring fatigue in clinical and community settings. J. Psychosom Res. 69, 17\u201322 (2010).","journal-title":"J. Psychosom Res."},{"key":"45072_CR45","volume-title":"The Doctor\u2019s Guide to Chronic Fatigue Syndrome: Understanding, Treating and Living with CFIDS","author":"DS Bell","year":"1995","unstructured":"Bell, D. S. The Doctor\u2019s Guide to Chronic Fatigue Syndrome: Understanding, Treating and Living with CFIDS (Da Capo Lifepost Books, 1995)."},{"key":"45072_CR46","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/jss.v088.i02","volume":"88","author":"J Love","year":"2019","unstructured":"Love, J. et al. JASP: Graphical statistical software for common statistical designs. J. Stat. Softw. 88, 1\u201317 (2019).","journal-title":"J. Stat. Softw."},{"key":"45072_CR47","doi-asserted-by":"publisher","first-page":"35","DOI":"10.3758\/s13423-017-1343-3","volume":"25","author":"E-J Wagenmakers","year":"2018","unstructured":"Wagenmakers, E.-J. et al. Bayesian inference for psychology. Part I: Theoretical advantages and practical ramifications. Psychon. Bull. Rev 25, 35\u201357 (2018).","journal-title":"Psychon. Bull. Rev"},{"key":"45072_CR48","doi-asserted-by":"publisher","first-page":"225","DOI":"10.3758\/PBR.16.2.225","volume":"16","author":"JN Rouder","year":"2009","unstructured":"Rouder, J. N., Speckman, P. L., Sun, D., Morey, R. D. & Iverson, G. Bayesian t tests for accepting and rejecting the null hypothesis. Psychon Bull. Rev. 16, 225\u2013237 (2009).","journal-title":"Psychon Bull. Rev."},{"key":"45072_CR49","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1016\/S0140-6736(22)01214-4","volume":"400","author":"AV Ballering","year":"2022","unstructured":"Ballering, A. V., Van Zon, S. K. R., Olde Hartman, T. C. & Rosmalen, J. G. M. Persistence of somatic symptoms after COVID-19 in the Netherlands: An observational cohort study. Lancet 400, 452\u2013461 (2022).","journal-title":"Lancet"},{"key":"45072_CR50","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1007\/s10654-013-9825-8","volume":"28","author":"B Simone","year":"2013","unstructured":"Simone, B. et al. Risk of venous thromboembolism associated with single and combined effects of Factor V Leiden, Prothrombin 20210A and Methylenetethraydrofolate reductase C677T: A meta-analysis involving over 11,000 cases and 21,000 controls. Eur. J. Epidemiol. 28, 621\u2013647 (2013).","journal-title":"Eur. J. Epidemiol."},{"key":"45072_CR51","doi-asserted-by":"publisher","first-page":"1812","DOI":"10.1038\/s41467-022-29513-z","volume":"13","author":"VT Tran","year":"2022","unstructured":"Tran, V. T., Porcher, R., Pane, I. & Ravaud, P. Course of post COVID-19 disease symptoms over time in the ComPaRe long COVID prospective e-cohort. Nat. Commun. 13, 1812 (2022).","journal-title":"Nat. Commun."},{"key":"45072_CR52","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1159\/000490354","volume":"87","author":"AWM Evers","year":"2018","unstructured":"Evers, A. W. M. et al. Implications of placebo and nocebo effects for clinical practice: Expert consensus. Psychother. Psychosom. 87, 204\u2013210 (2018).","journal-title":"Psychother. Psychosom."},{"key":"45072_CR53","doi-asserted-by":"publisher","first-page":"1016","DOI":"10.1001\/jama.299.9.1016","volume":"299","author":"RL Waber","year":"2008","unstructured":"Waber, R. L., Shiv, B., Carmon, Z. & Ariely, D. Commercial features of placebo and therapeutic efficacy. JAMA 299, 1016 (2008).","journal-title":"JAMA"},{"key":"45072_CR54","doi-asserted-by":"publisher","first-page":"110627","DOI":"10.1016\/j.mehy.2021.110627","volume":"153","author":"A Sen","year":"2021","unstructured":"Sen, A. Does serotonin deficiency lead to anosmia, ageusia, dysfunctional chemesthesis and increased severity of illness in COVID-19?. Med. Hypotheses 153, 110627 (2021).","journal-title":"Med. Hypotheses"},{"key":"45072_CR55","doi-asserted-by":"crossref","unstructured":"Luiz Gonzaga Francisco de Assis Barros D\u2019Elia, Z. The COVID-19 \u2018Bad Tryp\u2019 syndrome: NAD\/NADH+, tryptophan phenylalanine metabolism and thermogenesis like hecatomb\u2014The hypothesis of pathophysiology based on a compared COVID-19 and Yellow Fever Inflammatory Skeleton. J. Infect. Dis. Epidemiol. 8 (2022).","DOI":"10.23937\/2474-3658\/1510243"},{"key":"45072_CR56","doi-asserted-by":"publisher","first-page":"R814","DOI":"10.1152\/ajpregu.00337.2014","volume":"309","author":"VV Matchkov","year":"2015","unstructured":"Matchkov, V. V., Kravtsova, V. V., Wiborg, O., Aalkjaer, C. & Bouzinova, E. V. Chronic selective serotonin reuptake inhibition modulates endothelial dysfunction and oxidative state in rat chronic mild stress model of depression. Am. J. Physiol. Regul. Integr. Comp. Physiol. 309, R814\u2013R823 (2015).","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"45072_CR57","unstructured":"Farmacotherapeutisch Kompas. https:\/\/www.farmacotherapeutischkompas.nl\/."},{"key":"45072_CR58","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1177\/02698811211069110","volume":"36","author":"N Mariani","year":"2022","unstructured":"Mariani, N., Everson, J., Pariante, C. M. & Borsini, A. Modulation of microglial activation by antidepressants. J. Psychopharmacol. 36, 131\u2013150 (2022).","journal-title":"J. Psychopharmacol."},{"key":"45072_CR59","doi-asserted-by":"publisher","first-page":"29","DOI":"10.2147\/JEP.S63549","volume":"7","author":"NT Nguyen","year":"2015","unstructured":"Nguyen, N. T. et al. Aryl hydrocarbon receptor antagonism and its role in rheumatoid arthritis. J. Exp. Pharmacol. 7, 29\u201335. https:\/\/doi.org\/10.2147\/JEP.S63549 (2015).","journal-title":"J. Exp. Pharmacol."},{"key":"45072_CR60","doi-asserted-by":"publisher","unstructured":"Mcgovern, K. et al. 448\u2005Discovery of clinical candidate IK-175, a selective orally active AHR antagonist. In Regular and Young Investigator Award Abstracts A272.1-A272 (BMJ Publishing Group Ltd, 2020). https:\/\/doi.org\/10.1136\/jitc-2020-SITC2020.0448.","DOI":"10.1136\/jitc-2020-SITC2020.0448"},{"key":"45072_CR61","first-page":"181","volume":"59","author":"CP Rus","year":"2017","unstructured":"Rus, C. P. A girl with self-harm treated with N-acetylcysteine (NAC). Tijdschr. Psychiatr. 59, 181\u2013184 (2017).","journal-title":"Tijdschr. Psychiatr."},{"key":"45072_CR62","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/s42234-023-00104-7","volume":"9","author":"M Leitzke","year":"2023","unstructured":"Leitzke, M. Is the post-COVID-19 syndrome a severe impairment of acetylcholine-orchestrated neuromodulation that responds to nicotine administration?. Bioelectron. Med. 9, 2 (2023).","journal-title":"Bioelectron. Med."},{"key":"45072_CR63","doi-asserted-by":"publisher","first-page":"1609","DOI":"10.3892\/mmr.2014.2332","volume":"10","author":"M Zhang","year":"2014","unstructured":"Zhang, M., Wen, J., Wang, X. & Xiao, C. High-dose folic acid improves endothelial function by increasing tetrahydrobiopterin and decreasing homocysteine levels. Mol. Med. Rep. 10, 1609\u20131613 (2014).","journal-title":"Mol. Med. Rep."},{"key":"45072_CR64","doi-asserted-by":"publisher","first-page":"443","DOI":"10.3389\/fpsyt.2020.00443","volume":"11","author":"GE Tafet","year":"2020","unstructured":"Tafet, G. E. & Nemeroff, C. B. Pharmacological treatment of anxiety disorders: The role of the HPA axis. Front Psychiatry 11, 443 (2020).","journal-title":"Front Psychiatry"},{"key":"45072_CR65","doi-asserted-by":"publisher","first-page":"3800","DOI":"10.3390\/jcm11133800","volume":"11","author":"V Lebar","year":"2022","unstructured":"Lebar, V., Lagan\u00e0, A. S., Chiantera, V., Kuni\u010d, T. & Lukanovi\u0107, D. The Effect of COVID-19 on the menstrual cycle: A systematic review. J Clin Med 11, 3800 (2022).","journal-title":"J Clin Med"},{"key":"45072_CR66","doi-asserted-by":"publisher","first-page":"5809","DOI":"10.1038\/s41467-021-26096-z","volume":"12","author":"M Ferren","year":"2021","unstructured":"Ferren, M. et al. Hamster organotypic modeling of SARS-CoV-2 lung and brainstem infection. Nat. Commun. 12, 5809 (2021).","journal-title":"Nat. Commun."},{"key":"45072_CR67","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1159\/000026676","volume":"42","author":"S Oberndorfer","year":"2000","unstructured":"Oberndorfer, S., Saletu-Zyhlarz, G. & Saletu, B. Effects of selective serotonin reuptake inhibitors on objective and subjective sleep quality. Neuropsychobiology 42, 69\u201381 (2000).","journal-title":"Neuropsychobiology"},{"key":"45072_CR68","doi-asserted-by":"publisher","first-page":"989","DOI":"10.5664\/jcsm.5932","volume":"12","author":"N Aarts","year":"2016","unstructured":"Aarts, N. et al. Use of selective serotonin reuptake inhibitors and sleep quality: A population-based study. J. Clin. Sleep Med. 12, 989\u2013995 (2016).","journal-title":"J. Clin. Sleep Med."},{"key":"45072_CR69","volume-title":"The Archaeology of Mind: Neuroevolutionary Origins of Human Emotions","author":"J Panksepp","year":"2012","unstructured":"Panksepp, J. & Biven, L. The Archaeology of Mind: Neuroevolutionary Origins of Human Emotions (W. W. Norton & Company, 2012)."},{"key":"45072_CR70","doi-asserted-by":"publisher","first-page":"100056","DOI":"10.1016\/j.bbih.2020.100056","volume":"4","author":"G Halpert","year":"2020","unstructured":"Halpert, G., Amital, H. & Shoenfeld, Y. Dysregulation of G protein-coupled receptors of the autonomic nervous system, adrenergic and muscarinic acetylcholine receptors, in patients with autoimmune dysautonomic-related disorders. Brain Behav Immunol Health 4, 100056 (2020).","journal-title":"Brain Behav Immunol Health"},{"key":"45072_CR71","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1192\/apt.11.2.92","volume":"11","author":"N Medford","year":"2005","unstructured":"Medford, N., Sierra, M., Baker, D. & David, A. S. Understanding and treating depersonalisation disorder. Adv. Psychiatric Treat. 11, 92\u2013100 (2005).","journal-title":"Adv. Psychiatric Treat."},{"key":"45072_CR72","doi-asserted-by":"publisher","first-page":"343","DOI":"10.2165\/00023210-200418060-00002","volume":"18","author":"D Simeon","year":"2004","unstructured":"Simeon, D. Depersonalisation disorder. CNS Drugs 18, 343\u2013354 (2004).","journal-title":"CNS Drugs"},{"key":"45072_CR73","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1586\/14737175.8.1.19","volume":"8","author":"M Sierra","year":"2008","unstructured":"Sierra, M. Depersonalization disorder: Pharmacological approaches. Expert Rev. Neurother. 8, 19\u201326 (2008).","journal-title":"Expert Rev. Neurother."},{"key":"45072_CR74","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1017\/S1092852915000425","volume":"21","author":"E Dale","year":"2016","unstructured":"Dale, E. et al. Effects of serotonin in the hippocampus: How SSRIs and multimodal antidepressants might regulate pyramidal cell function. CNS Spectr. 21, 143\u2013161 (2016).","journal-title":"CNS Spectr."},{"key":"45072_CR75","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0267423","author":"H Nakhaee","year":"2022","unstructured":"Nakhaee, H. et al. The effect of antidepressants on the severity of COVID-19 in hospitalized patients: A systematic review and meta-analysis. PLoS ONE https:\/\/doi.org\/10.1371\/journal.pone.0267423 (2022).","journal-title":"PLoS ONE"},{"key":"45072_CR76","doi-asserted-by":"publisher","first-page":"368","DOI":"10.3390\/brainsci13020368","volume":"13","author":"J Dao","year":"2023","unstructured":"Dao, J. et al. A Systematic review on the potential of aspirin to reduce cardiovascular risk in schizophrenia. Brain Sci. 13, 368 (2023).","journal-title":"Brain Sci."},{"key":"45072_CR77","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1016\/j.ijcard.2008.10.010","volume":"139","author":"J Lekakis","year":"2010","unstructured":"Lekakis, J. et al. Selective serotonin re-uptake inhibitors decrease the cytokine-induced endothelial adhesion molecule expression, the endothelial adhesiveness to monocytes and the circulating levels of vascular adhesion molecules. Int. J. Cardiol. 139, 150\u2013158 (2010).","journal-title":"Int. J. Cardiol."},{"key":"45072_CR78","doi-asserted-by":"publisher","unstructured":"Visser, D. et al. Long COVID is associated with extensive in-vivo neuroinflammation on [18 F]DPA-714 PET. medRxiv 2022.06.02.22275916 (2022). https:\/\/doi.org\/10.1101\/2022.06.02.22275916.","DOI":"10.1101\/2022.06.02.22275916"},{"key":"45072_CR79","doi-asserted-by":"publisher","unstructured":"Shen, W.-B. et al. SARS-CoV-2 invades cognitive centers of the brain and induces Alzheimer\u2019s-like neuropathology. bioRxiv 2022.01.31.478476 (2022). https:\/\/doi.org\/10.1101\/2022.01.31.478476.","DOI":"10.1101\/2022.01.31.478476"},{"key":"45072_CR80","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.1176\/ps.2008.59.10.1121","volume":"59","author":"R Hansen","year":"2008","unstructured":"Hansen, R. et al. Meta-analysis of major depressive disorder relapse and recurrence with second-generation antidepressants. Psychiatric Serv. 59, 1121\u20131130 (2008).","journal-title":"Psychiatric Serv."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-023-45072-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-023-45072-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-023-45072-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,2]],"date-time":"2023-11-02T07:06:12Z","timestamp":1698908772000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-023-45072-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,2]]},"references-count":80,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["45072"],"URL":"https:\/\/doi.org\/10.1038\/s41598-023-45072-9","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-3153645\/v1","asserted-by":"object"},{"id-type":"doi","id":"10.21203\/rs.3.rs-3153645\/v2","asserted-by":"object"}]},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,2]]},"assertion":[{"value":"9 July 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 October 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 November 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"18599"}}