{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:59:58Z","timestamp":1787068798248,"version":"build-2736575974"},"reference-count":21,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2020,7,27]],"date-time":"2020-07-27T00:00:00Z","timestamp":1595808000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The article processing charge was funded by the German Research Foundation (DFG) and the University of Freiburg in the funding program Open Access Publishing.","award":["n.a."],"award-info":[{"award-number":["n.a."]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Introduction: The risk of developing depression is increased in patients with autoimmune thyroiditis. Autoimmune Hashimoto thyroiditis is diagnosed using the serum markers anti-thyroid peroxidase (TPO) and anti-thyroglobulin (TG) antibodies. In rare cases, patients with autoimmune thyroiditis can also suffer from the heterogeneous and ill-defined syndrome of Hashimoto encephalopathy. Biomarkers for Hashimoto encephalopathy or for any brain involvement of autoimmune thyroiditis are currently lacking. The aim of the present descriptive study was therefore to determine whether a subgroup of seropositive patients shows intrathecal anti-thyroid antibody synthesis in the cerebrospinal fluid (CSF). Participants and methods: Paired serum and CSF samples from 100 patients with unipolar depression were examined for anti-TPO and anti-TG antibodies using enzyme-linked immunosorbent assays. Antibody-specific indices (ASIs) were calculated for seropositive samples. These ASIs allow the differentiation between the brain-derived fraction of antibodies and antibodies which are passively diffused from the serum. ASIs &gt;1.4 were assessed as positive for brain-derived antibodies. Additionally, for explorative evaluations, a stricter ASI limit of &gt;2 was applied. Results: Anti-TPO antibodies were increased in the serum of 16 patients (16%); increased anti-TPO ASIs (&gt;1.4) were detected in 11 of these patients (69%). Anti-TG antibodies in the serum were detected in three patients (3%), with two of them (67%) showing increased ASIs (&gt;1.4). Overall, the authors found increased anti-thyroid antibodies in 17 of 100 patients (17%), with 13 out of 17 patients showing increased ASIs (76%; range 1.4\u20134.1). Choosing ASI levels of &gt;2 led to positive findings in six out of 16 patients (38%) with anti-TPO antibodies in their serum but no increase in ASIs in three patients (0%) who were seropositive for anti-TG antibodies. The patients with elevated ASIs (N = 13) were younger than the ASI-negative patients (N = 87; p = 0.009); no differences were noted in the frequency of CSF, electroencephalography, and\/or magnetic resonance imaging alterations. Discussion: A subgroup of seropositive patients showed intrathecal synthesis of anti-TPO and, more rarely, of anti-TG antibodies, which might be an indication of central autoimmunity in a subgroup of patients with unipolar depression. The confirmation of elevated ASIs as a biomarker for Hashimoto encephalopathy must await further studies. The relevance of the findings is limited by the study\u2019s retrospective and uncontrolled design.<\/jats:p>","DOI":"10.3390\/jcm9082391","type":"journal-article","created":{"date-parts":[[2020,7,27]],"date-time":"2020-07-27T09:24:49Z","timestamp":1595841889000},"page":"2391","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Anti-Thyroid Peroxidase and Anti-Thyroglobulin Autoantibodies in the Cerebrospinal Fluid of Patients with Unipolar Depression"],"prefix":"10.3390","volume":"9","author":[{"given":"Rick","family":"Dersch","sequence":"first","affiliation":[{"name":"Clinic of Neurology and Neurophysiology, Medical Center\u2014University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2274-5447","authenticated-orcid":false,"given":"Ludger","family":"Tebartz van Elst","sequence":"additional","affiliation":[{"name":"Section for Experimental Neuropsychiatry, Department of Psychiatry and Psychotherapy, Medical Center\u2014University of Freiburg, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany"},{"name":"Department of Psychiatry and Psychotherapy, Medical Center\u2014University of Freiburg, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedikt","family":"Hochstuhl","sequence":"additional","affiliation":[{"name":"Section for Experimental Neuropsychiatry, Department of Psychiatry and Psychotherapy, Medical Center\u2014University of Freiburg, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany"},{"name":"Department of Psychiatry and Psychotherapy, Medical Center\u2014University of Freiburg, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany"},{"name":"Department of Medicine, Hospital Mutterhaus of the Borrom\u00e4erinnen, 54290 Trier, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9261-6771","authenticated-orcid":false,"given":"Bernd L.","family":"Fiebich","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, Medical Center\u2014University of Freiburg, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Stich","sequence":"additional","affiliation":[{"name":"Clinic of Neurology and Neurophysiology, Medical Center\u2014University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany"},{"name":"Medical Care Center, Neurology, 78464 Konstanz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tilman","family":"Robinson","sequence":"additional","affiliation":[{"name":"Clinic of Neurology and Neurophysiology, Medical Center\u2014University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Matysik","sequence":"additional","affiliation":[{"name":"Section for Experimental Neuropsychiatry, Department of Psychiatry and Psychotherapy, Medical Center\u2014University of Freiburg, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany"},{"name":"Department of Psychiatry and Psychotherapy, Medical Center\u2014University of Freiburg, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maike","family":"Michel","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, Medical Center\u2014University of Freiburg, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0263-4360","authenticated-orcid":false,"given":"Kimon","family":"Runge","sequence":"additional","affiliation":[{"name":"Section for Experimental Neuropsychiatry, Department of Psychiatry and Psychotherapy, Medical Center\u2014University of Freiburg, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany"},{"name":"Department of Psychiatry and Psychotherapy, Medical Center\u2014University of Freiburg, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathrin","family":"Nickel","sequence":"additional","affiliation":[{"name":"Section for Experimental Neuropsychiatry, Department of Psychiatry and Psychotherapy, Medical Center\u2014University of Freiburg, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany"},{"name":"Department of Psychiatry and Psychotherapy, Medical Center\u2014University of Freiburg, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Domschke","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, Medical Center\u2014University of Freiburg, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany"},{"name":"Center for Basics in Neuromodulation, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Endres","sequence":"additional","affiliation":[{"name":"Section for Experimental Neuropsychiatry, Department of Psychiatry and Psychotherapy, Medical Center\u2014University of Freiburg, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany"},{"name":"Department of Psychiatry and Psychotherapy, Medical Center\u2014University of Freiburg, Faculty of Medicine, University of 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Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1001\/archneur.60.2.164","article-title":"Hashimoto encephalopathy: Syndrome or myth?","volume":"60","author":"Chong","year":"2003","journal-title":"Arch. Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1001\/archneur.63.2.197","article-title":"Steroid-Responsive Encephalopathy Associated with Autoimmune Thyroiditis","volume":"63","author":"Castillo","year":"2006","journal-title":"Arch. Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Endres, D., Perlov, E., Stich, O., and Tebartz van Elst, L. (2016). Steroid responsive encephalopathy associated with autoimmune thyroiditis (SREAT) presenting as major depression. BMC Psychiatry, 16.","DOI":"10.1186\/s12888-016-0897-3"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1016\/j.autrev.2016.09.008","article-title":"Steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT): Characteristics, treatment and outcome in 251 cases from the literature","volume":"15","author":"Laurent","year":"2016","journal-title":"Autoimmun. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1007\/s00115-019-0700-z","article-title":"[Autoantibody-associated schizophreniform psychoses: Clinical symptomatology]","volume":"90","author":"Endres","year":"2019","journal-title":"Der Nervenarzt"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/S1474-4422(15)00401-9","article-title":"A clinical approach to diagnosis of autoimmune encephalitis","volume":"15","author":"Graus","year":"2016","journal-title":"Lancet Neurol."},{"key":"ref_9","first-page":"e217","article-title":"Hashimoto encephalopathy in the 21st century","volume":"94","author":"Mattozzi","year":"2019","journal-title":"Neurology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1210\/jcem.87.2.8182","article-title":"Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III)","volume":"87","author":"Hollowell","year":"2002","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1212\/01.WNL.0000048660.71390.C6","article-title":"Antithyroid antibodies in the CSF","volume":"60","author":"Ferracci","year":"2003","journal-title":"Neurology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1176\/appi.neuropsych.16110296","article-title":"Intrathecal Thyroid Autoantibody Synthesis in a Subgroup of Patients with Schizophreniform Syndromes","volume":"29","author":"Endres","year":"2017","journal-title":"J. Neuropsychiatry Clin. Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/S0022-510X(00)00501-3","article-title":"Cerebrospinal fluid analysis: Disease-related data patterns and evaluation programs","volume":"184","author":"Reiber","year":"2001","journal-title":"J. Neurol. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1111\/bdi.12244","article-title":"An observational study of inflammation in the central nervous system in patients with bipolar disorder","volume":"17","author":"Stich","year":"2014","journal-title":"Bipolar Disord."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1007\/s00415-018-8779-x","article-title":"The MRZ reaction and a quantitative intrathecal IgG synthesis may be helpful to differentiate between primary central nervous system lymphoma and multiple sclerosis","volume":"265","author":"Hottenrott","year":"2018","journal-title":"J. Neurol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.jneuroim.2007.08.012","article-title":"Anti-thyroperoxidase antibodies from patients with Hashimoto\u2019s encephalopathy bind to cerebellar astrocytes","volume":"192","author":"Blanchin","year":"2007","journal-title":"J. Neuroimmunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.jns.2010.11.027","article-title":"Immuno-localisation of anti-thyroid antibodies in adult human cerebral cortex","volume":"302","author":"Moodley","year":"2011","journal-title":"J. Neurol. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1007\/s11011-017-0076-3","article-title":"Expression of thyroid-stimulating hormone receptors and thyroglobulin in limbic regions in the adult human brain","volume":"33","author":"Naicker","year":"2017","journal-title":"Metab. Brain Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/S2215-0366(19)30290-1","article-title":"Autoimmune psychosis: An international consensus on an approach to the diagnosis and management of psychosis of suspected autoimmune origin","volume":"7","author":"Pollak","year":"2020","journal-title":"Lancet Psychiatry"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1007\/s00415-016-8360-4","article-title":"The MRZ reaction as a highly specific marker of multiple sclerosis: Re-evaluation and structured review of the literature","volume":"264","author":"Jarius","year":"2016","journal-title":"J. Neurol."},{"key":"ref_21","first-page":"751","article-title":"Lyme Neuroborreliosis","volume":"115","author":"Rauer","year":"2018","journal-title":"Dtsch. Aerzteblatt Online"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/9\/8\/2391\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:51:57Z","timestamp":1760176317000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/9\/8\/2391"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,27]]},"references-count":21,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2020,8]]}},"alternative-id":["jcm9082391"],"URL":"https:\/\/doi.org\/10.3390\/jcm9082391","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,27]]}}}