{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T17:31:25Z","timestamp":1772127085120,"version":"3.50.1"},"reference-count":22,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2022,5,12]],"date-time":"2022-05-12T00:00:00Z","timestamp":1652313600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,5,12]],"date-time":"2022-05-12T00:00:00Z","timestamp":1652313600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100006254","name":"Ruhr-Universit\u00e4t Bochum","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100006254","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neurol"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Objective<\/jats:title>\n                <jats:p>Long coronavirus disease (Long-COVID) syndrome is a hitherto poorly understood phenomenon with a broad spectrum of symptoms, including depression and anxiety. Depressive symptoms have been associated with brainstem raphe (BR) alterations in transcranial sonography (TCS) that might reflect dysfunction of the serotonergic system. The primary aim was to investigate the connection of BR alterations with depressive and anxiety symptoms in patients with Long-COVID syndrome.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>In a cross-sectional study design, we included outpatients fulfilling the criteria of Long-COVID syndrome. All patients were examined by TCS in the axial plane with focus on BR signal alterations. The Hospital Anxiety and Depression Scale (HADS) was used to test for symptoms of anxiety and depression.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>We included <jats:italic>n<\/jats:italic>\u2009=\u200970 patients with Long-COVID syndrome, of which 28.6% (<jats:italic>n<\/jats:italic>\u2009=\u200920) exhibited a reduced echogenicity of BR in the TCS examination. Patients with hypoechogenic BR had higher subscores for anxiety and depression compared to normoechogenic patients (HADS depression: median 8 versus 5.5, <jats:italic>p<\/jats:italic>\u2009=\u20090.006; HADS anxiety: median 9 versus 6.5, <jats:italic>p<\/jats:italic>\u2009=\u20090.006). After adjustment for reasonable confounders, only the odds ratio (OR) for relevant depressive symptoms was higher among Long-COVID patients with hypoechogenic raphe (adjusted OR 3.884, 95% CI 1.244\u201312.123).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Discussion<\/jats:title>\n                <jats:p>Hypoechogenic BR alterations are independently associated with depressive symptoms in Long-COVID patients but are not highly frequent. Future studies should investigate whether the hypoechogenicity of the BR is a direct consequence or whether it reflects a priori a higher susceptibility to depressive symptoms after COVID-19, thus enabling to identify COVID-19 patients at higher risk of developing Long-COVID depressive symptoms.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00415-022-11154-3","type":"journal-article","created":{"date-parts":[[2022,5,12]],"date-time":"2022-05-12T18:03:41Z","timestamp":1652378621000},"page":"4604-4610","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Hypoechogenicity of brainstem raphe in long-COVID syndrome\u2013less common but independently associated with depressive symptoms: a cross-sectional study"],"prefix":"10.1007","volume":"269","author":[{"given":"Daniel","family":"Richter","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hannah","family":"Schulze","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeyanthan Charles","family":"James","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadine","family":"Siems","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadine","family":"Trampe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ralf","family":"Gold","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christos","family":"Krogias","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3412-762X","authenticated-orcid":false,"given":"Simon","family":"Faissner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,5,12]]},"reference":[{"key":"11154_CR1","doi-asserted-by":"publisher","first-page":"175628642093203","DOI":"10.1177\/1756286420932036","volume":"13","author":"G Tsivgoulis","year":"2020","unstructured":"Tsivgoulis G, Palaiodimou L, Katsanos AH et al (2020) Neurological manifestations and implications of COVID-19 pandemic. Ther Adv Neurol Disord 13:1756286420932036. https:\/\/doi.org\/10.1177\/1756286420932036","journal-title":"Ther Adv Neurol Disord"},{"issue":"8","key":"11154_CR2","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1056\/NEJMoa2001017","volume":"382","author":"N Zhu","year":"2020","unstructured":"Zhu N, Zhang D, Wang W et al (2020) A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med 382(8):727\u2013733. https:\/\/doi.org\/10.1056\/NEJMoa2001017","journal-title":"N Engl J Med"},{"issue":"2","key":"11154_CR3","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1111\/jon.12819","volume":"31","author":"T Ladopoulos","year":"2021","unstructured":"Ladopoulos T, Zand R, Shahjouei S et al (2021) COVID-19: neuroimaging features of a pandemic. J Neuroimaging 31(2):228\u2013243. https:\/\/doi.org\/10.1111\/jon.12819","journal-title":"J Neuroimaging"},{"issue":"10270","key":"11154_CR4","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1016\/S0140-6736(20)32656-8","volume":"397","author":"C Huang","year":"2021","unstructured":"Huang C, Huang L, Wang Y et al (2021) 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study. Lancet 397(10270):220\u2013232. https:\/\/doi.org\/10.1016\/S0140-6736(20)32656-8","journal-title":"Lancet"},{"issue":"3","key":"11154_CR5","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1503\/jpn.100067","volume":"36","author":"C Krogias","year":"2011","unstructured":"Krogias C, Strassburger K, Eyding J et al (2011) Depression in patients with Huntington disease correlates with alterations of the brain stem raphe depicted by transcranial sonography. J Psychiatry Neurosci 36(3):187\u2013194. https:\/\/doi.org\/10.1503\/jpn.100067","journal-title":"J Psychiatry Neurosci"},{"key":"11154_CR6","doi-asserted-by":"publisher","first-page":"645","DOI":"10.3389\/fneur.2018.00645","volume":"9","author":"D Richter","year":"2018","unstructured":"Richter D, Woitalla D, Muhlack S, Gold R, T\u00f6nges L, Krogias C (2018) Brainstem raphe alterations in TCS: a biomarker for depression and apathy in Parkinson\u2019s disease patients. Front Neurol 9:645. https:\/\/doi.org\/10.3389\/fneur.2018.00645","journal-title":"Front Neurol"},{"key":"11154_CR7","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2019.106589","volume":"102","author":"J Shen","year":"2020","unstructured":"Shen J, Li DL, Tan XX et al (2020) A transcranial sonography study of brainstem and its association with depression in idiopathic generalized epilepsy with tonic-clonic seizures. Epilepsy Behav 102:106589. https:\/\/doi.org\/10.1016\/j.yebeh.2019.106589","journal-title":"Epilepsy Behav"},{"key":"11154_CR8","doi-asserted-by":"publisher","first-page":"175628642110077","DOI":"10.1177\/17562864211007708","volume":"14","author":"Y Zhang","year":"2021","unstructured":"Zhang Y, Liu Y, Han R, Liu K, Xing Y (2021) Hypoechogenicity of the midbrain raphe detected by transcranial sonography: an imaging biomarker for depression in migraine patients. Ther Adv Neurol Disord 14:17562864211007708. https:\/\/doi.org\/10.1177\/17562864211007708","journal-title":"Ther Adv Neurol Disord"},{"issue":"3","key":"11154_CR9","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1111\/jon.12328","volume":"26","author":"C Krogias","year":"2016","unstructured":"Krogias C, Walter U (2016) Transcranial sonography findings in depression in association with psychiatric and neurologic diseases: a review. J Neuroimaging 26(3):257\u2013263. https:\/\/doi.org\/10.1111\/jon.12328","journal-title":"J Neuroimaging"},{"issue":"10","key":"11154_CR10","doi-asserted-by":"publisher","first-page":"1743","DOI":"10.1002\/jmv.25826","volume":"92","author":"S Nataf","year":"2020","unstructured":"Nataf S (2020) An alteration of the dopamine synthetic pathway is possibly involved in the pathophysiology of COVID-19. J Med Virol 92(10):1743\u20131744. https:\/\/doi.org\/10.1002\/jmv.25826","journal-title":"J Med Virol"},{"issue":"1","key":"11154_CR11","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.ejpsy.2020.10.004","volume":"35","author":"L Attademo","year":"2021","unstructured":"Attademo L, Bernardini F (2021) Are dopamine and serotonin involved in COVID-19 pathophysiology? Eur J Psychiatry 35(1):62\u201363. https:\/\/doi.org\/10.1016\/j.ejpsy.2020.10.004","journal-title":"Eur J Psychiatry"},{"issue":"5","key":"11154_CR12","doi-asserted-by":"publisher","first-page":"642","DOI":"10.23736\/S1973-9087.20.06501-6","volume":"56","author":"MG Ceravolo","year":"2020","unstructured":"Ceravolo MG, Arienti C, de Sire A et al (2020) Rehabilitation and COVID-19: the cochrane rehabilitation 2020 rapid living systematic review. Eur J Phys Rehabil Med 56(5):642\u2013651. https:\/\/doi.org\/10.23736\/S1973-9087.20.06501-6","journal-title":"Eur J Phys Rehabil Med"},{"issue":"8","key":"11154_CR13","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1016\/S1473-3099(20)30483-7","volume":"20","author":"WHO Working Group on the Clinical Characterisation and Management of COVID-19 infection","year":"2020","unstructured":"WHO Working Group on the Clinical Characterisation and Management of COVID-19 infection (2020) A minimal common outcome measure set for COVID-19 clinical research. The Lancet Infect Dis 20(8):192\u20137","journal-title":"The Lancet Infect Dis"},{"issue":"6","key":"11154_CR14","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1111\/j.1600-0447.1983.tb09716.x","volume":"67","author":"AS Zigmond","year":"1983","unstructured":"Zigmond AS, Snaith RP (1983) The hospital anxiety and depression scale. Acta Psychiatr Scand 67(6):361\u2013370. https:\/\/doi.org\/10.1111\/j.1600-0447.1983.tb09716.x","journal-title":"Acta Psychiatr Scand"},{"issue":"4","key":"11154_CR15","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1055\/s-0033-1356415","volume":"35","author":"U Walter","year":"2014","unstructured":"Walter U, \u0160koloud\u00edk D (2014) Transcranial sonography (TCS) of brain parenchyma in movement disorders: quality standards, diagnostic applications and novel technologies. Ultraschall Med 35(4):322\u2013331. https:\/\/doi.org\/10.1055\/s-0033-1356415","journal-title":"Ultraschall Med"},{"issue":"6","key":"11154_CR16","doi-asserted-by":"publisher","first-page":"756","DOI":"10.1016\/S1473-3099(21)00136-5","volume":"21","author":"AL Kondratiuk","year":"2021","unstructured":"Kondratiuk AL, Pillay TD, Kon OM, Lalvani A (2021) A conceptual framework to accelerate the clinical impact of evolving research into long COVID. Lancet Infect Dis 21(6):756\u2013757. https:\/\/doi.org\/10.1016\/S1473-3099(21)00136-5","journal-title":"Lancet Infect Dis"},{"issue":"4","key":"11154_CR17","doi-asserted-by":"publisher","first-page":"576","DOI":"10.7326\/M20-5661","volume":"174","author":"V Chopra","year":"2021","unstructured":"Chopra V, Flanders SA, O\u2019Malley M, Malani AN, Prescott HC (2021) Sixty-day outcomes among patients hospitalized with COVID-19. Ann Intern Med 174(4):576\u2013578. https:\/\/doi.org\/10.7326\/M20-5661","journal-title":"Ann Intern Med"},{"issue":"22","key":"11154_CR18","doi-asserted-by":"publisher","first-page":"2292","DOI":"10.1001\/jama.2020.22760","volume":"324","author":"EJ Lenze","year":"2020","unstructured":"Lenze EJ, Mattar C, Zorumski CF et al (2020) Fluvoxamine vs placebo and clinical deterioration in outpatients with symptomatic COVID-19: a randomized clinical trial. JAMA 324(22):2292\u20132300. https:\/\/doi.org\/10.1001\/jama.2020.22760","journal-title":"JAMA"},{"issue":"6","key":"11154_CR19","doi-asserted-by":"publisher","first-page":"0253458","DOI":"10.1371\/journal.pone.0253458","volume":"16","author":"G Mpekoulis","year":"2021","unstructured":"Mpekoulis G, Frakolaki E, Taka S et al (2021) Alteration of L-Dopa decarboxylase expression in SARS-CoV-2 infection and its association with the interferon-inducible ACE2 isoform. PLoS One 16(6):0253458. https:\/\/doi.org\/10.1371\/journal.pone.0253458","journal-title":"PLoS One"},{"key":"11154_CR20","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbih.2021.100387","volume":"18","author":"F Benedetti","year":"2021","unstructured":"Benedetti F, Palladini M, Paolini M et al (2021) Brain correlates of depression, post-traumatic distress, and inflammatory biomarkers in COVID-19 survivors: a multimodal magnetic resonance imaging study. Brain Behav Immun Health 18:100387. https:\/\/doi.org\/10.1016\/j.bbih.2021.100387","journal-title":"Brain Behav Immun Health"},{"issue":"1","key":"11154_CR21","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.pscychresns.2006.12.001","volume":"155","author":"U Walter","year":"2007","unstructured":"Walter U, Prudente-Morrissey L, Herpertz SC, Benecke R, Hoeppner J (2007) Relationship of brainstem raphe echogenicity and clinical findings in depressive states. Psychiatry Res 155(1):67\u201373. https:\/\/doi.org\/10.1016\/j.pscychresns.2006.12.001","journal-title":"Psychiatry Res"},{"issue":"5","key":"11154_CR22","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1136\/jnnp.63.5.590","volume":"63","author":"T Becker","year":"1997","unstructured":"Becker T, Becker G, Seufert J et al (1997) Parkinson\u2019s disease and depression: evidence for an alteration of the basal limbic system detected by transcranial sonography. J Neurol Neurosurg Psychiatry 63(5):590\u2013596. https:\/\/doi.org\/10.1136\/jnnp.63.5.590","journal-title":"J Neurol Neurosurg Psychiatry"}],"container-title":["Journal of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00415-022-11154-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00415-022-11154-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00415-022-11154-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,9]],"date-time":"2022-08-09T15:12:33Z","timestamp":1660057953000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00415-022-11154-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,12]]},"references-count":22,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2022,9]]}},"alternative-id":["11154"],"URL":"https:\/\/doi.org\/10.1007\/s00415-022-11154-3","relation":{},"ISSN":["0340-5354","1432-1459"],"issn-type":[{"value":"0340-5354","type":"print"},{"value":"1432-1459","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,12]]},"assertion":[{"value":"9 March 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 April 2022","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 April 2022","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 May 2022","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"None.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}},{"value":"All patients were included after detailed information about the study and gave written informed consent. In accordance with the Helsinki Declaration of 1975, the study was approved by the local university ethics committee of the Ruhr University Bochum, Germany (approval no. 20\u20136827).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}]}}