{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T16:21:46Z","timestamp":1789662106806,"version":"4.0.1"},"reference-count":56,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T00:00:00Z","timestamp":1675209600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T00:00:00Z","timestamp":1675209600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Thyroid\u00ae"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>The hypothalamus-pituitary-thyroid axis coordinates brain development and postdevelopmental function. Thyroid hormone (TH) variations, even within the normal range, have been associated with the risk of developing common psychiatric disorders, although the underlying mechanisms remain poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>To get new insight into the potentially shared mechanisms underlying thyroid dysfunction and psychiatric disorders, we performed a comprehensive analysis of multiple phenotypic and genotypic databases. We investigated the relationship of thyroid disorders with depression, bipolar disorder (BIP), and anxiety disorders (ANXs) in 497,726 subjects from U.K. Biobank. We subsequently investigated genetic correlations between thyroid disorders, thyrotropin (TSH), and free thyroxine (fT4) levels, with the genome-wide factors that predispose to psychiatric disorders. Finally, the observed global genetic correlations were furthermore pinpointed to specific local genomic regions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Hypothyroidism was positively associated with an increased risk of major depressive disorder (MDD; OR\u2009=\u20091.31,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20095.29\u2009\u00d7\u200910\n                      <jats:sup>\u221289<\/jats:sup>\n                      ), BIP (OR\u2009=\u20091.55,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.0038), and ANX (OR\u2009=\u20091.16,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20096.22\u2009\u00d7\u200910\n                      <jats:sup>\u22128<\/jats:sup>\n                      ). Hyperthyroidism was associated with MDD (OR\u2009=\u20091.11,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.0034) and ANX (OR\u2009=\u20091.34,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20095.99\u2009\u00d7\u200910\n                      <jats:sup>\u2212<\/jats:sup>\n                      \u2076). Genetically, strong coheritability was observed between thyroid disease and both major depressive (\n                      <jats:italic toggle=\"yes\">r<\/jats:italic>\n                      <jats:sub>g<\/jats:sub>\n                      \u2009=\u20090.17,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20092.7\u2009\u00d7\u200910\n                      <jats:sup>\u2212<\/jats:sup>\n                      \u2074) and ANXs (\n                      <jats:italic toggle=\"yes\">r<\/jats:italic>\n                      <jats:sub>g<\/jats:sub>\n                      \u2009=\u20090.17,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20096.7\u2009\u00d7\u200910\n                      <jats:sup>\u2212<\/jats:sup>\n                      \u2076). This genetic correlation was particularly strong at the major histocompatibility complex locus on chromosome 6 (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009&lt;\u200910\n                      <jats:sup>\u2212<\/jats:sup>\n                      \u2075), but further analysis showed that other parts of the genome also contributed to this global effect. Importantly, neither TSH nor fT4 levels were genetically correlated with mood disorders.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Our findings highlight an underlying association between autoimmune hypothyroidism and mood disorders, which is not mediated through THs and in which autoimmunity plays a prominent role. While these findings could shed new light on the potential ineffectiveness of treating (minor) variations in thyroid function in psychiatric disorders, further research is needed to identify the exact underlying molecular mechanisms.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/thy.2022.0304","type":"journal-article","created":{"date-parts":[[2022,12,4]],"date-time":"2022-12-04T05:13:07Z","timestamp":1670130787000},"page":"159-168","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":40,"title":["Exploring the Genetic Link Between Thyroid Dysfunction and Common Psychiatric Disorders: A Specific Hormonal or a General Autoimmune Comorbidity"],"prefix":"10.1177","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3571-1270","authenticated-orcid":false,"given":"Sourena","family":"Soheili-Nezhad","sequence":"first","affiliation":[{"name":"Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, the Netherlands."},{"name":"Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, the Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Sprooten","sequence":"additional","affiliation":[{"name":"Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, the Netherlands."},{"name":"Department of Human Genetics, Radboud University Medical Centre, Nijmegen, the Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Indira","family":"Tendolkar","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, the Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Medici","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Academic Center for Thyroid Diseases, Rotterdam, the Netherlands."},{"name":"Department of Epidemiology, Erasmus Medical Centre, Rotterdam, the Netherlands."},{"name":"Division of Endocrinology, Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, the Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2023,2,14]]},"reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncpendmet0424"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.1159\/000492129"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.psychres.2012.05.010"},{"key":"e_1_3_6_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2826.2008.01774.x"},{"key":"e_1_3_6_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.2008.03352.x"},{"key":"e_1_3_6_7_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2013-3589"},{"key":"e_1_3_6_8_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2021.2506"},{"key":"e_1_3_6_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-75776-1"},{"key":"e_1_3_6_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-020-01961-y"},{"key":"e_1_3_6_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2013.09.023"},{"key":"e_1_3_6_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2014.03.008"},{"key":"e_1_3_6_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/da.22692"},{"key":"e_1_3_6_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF03344150"},{"key":"e_1_3_6_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/s42000-021-00312-3"},{"key":"e_1_3_6_16_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2003-031641"},{"key":"e_1_3_6_17_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291721000829"},{"key":"e_1_3_6_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-019-0634-7"},{"key":"e_1_3_6_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2019.03.022"},{"key":"e_1_3_6_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06356-1"},{"key":"e_1_3_6_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17718-z"},{"key":"e_1_3_6_22_2","doi-asserted-by":"publisher","unstructured":"Cross-Disorder Group of the Psychiatric Genomics Consortium. 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