{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:27:20Z","timestamp":1787066840991,"version":"build-2736575974"},"reference-count":66,"publisher":"SAGE Publications","issue":"8","license":[{"start":{"date-parts":[[2021,8,1]],"date-time":"2021-08-01T00:00:00Z","timestamp":1627776000000},"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":[[2021,8]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Observational studies suggest that even minor variations in thyroid function are associated with the risk of mood disorders, including major depressive disorder (MDD) and bipolar disorder (BD). However, it is unknown whether these associations are causal or not. We used a Mendelian randomization (MR) approach to investigate causal effects of minor variations in thyrotropin (TSH) and free thyroxine (fT4) levels on MDD and BD risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods:<\/jats:title>\n                    <jats:p>\n                      We performed two-sample MR analyses using data from the largest publicly available genome-wide association studies on normal-range TSH (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      \u2009=\u200954,288) and fT4 (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      \u2009=\u200949,269) levels, MDD (170,756 cases, 329,443 controls) and BD (20,352 cases, 31,358 controls). Secondary MR analyses investigated the effects of TSH and fT4 levels on specific MDD and BD subtypes. Reverse MR was also performed to assess the effects of MDD and BD on TSH and fT4 levels.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      There were no associations between genetically predicted TSH and fT4 levels and MDD risk, nor MDD subtypes and minor depressive symptoms. A one standard deviation increase in fT4 levels was nominally associated with an 11% decrease in the overall BD risk (odds ratio [OR]\u2009=\u20090.89, 95% confidence interval [CI]\u2009=\u20090.80\u20130.98,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.022) and a 13% decrease in the BD type 1 risk (OR\u2009=\u20090.87, CI\u2009=\u20090.75\u20131.00,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.047). In the reverse direction, genetic predisposition to MDD and BD was not associated with TSH nor fT4 levels.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Variations in normal-range TSH and fT4 levels have no effects on the risk of MDD and its subtypes, and neither on minor depressive symptoms. This indicates that depressive symptoms should not be attributed to minor variations in thyroid function. Borderline associations with BD and BD type 1 risks suggest that further clinical studies should investigate the effect of thyroid hormone treatment in BD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/thy.2020.0884","type":"journal-article","created":{"date-parts":[[2021,4,24]],"date-time":"2021-04-24T05:38:28Z","timestamp":1619242708000},"page":"1171-1181","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":57,"title":["Thyroid Function and Mood Disorders: A Mendelian Randomization Study"],"prefix":"10.1177","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5422-6900","authenticated-orcid":false,"given":"Aleksander","family":"Ku\u015b","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Academic Center for Thyroid Diseases, Erasmus Medical Center, Rotterdam, The Netherlands."},{"name":"Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands."},{"name":"Department of Internal Medicine and Endocrinology, Medical University of Warsaw, Warsaw, Poland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3899-1324","authenticated-orcid":false,"given":"Alisa D.","family":"Kjaergaard","sequence":"additional","affiliation":[{"name":"Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eirini","family":"Marouli","sequence":"additional","affiliation":[{"name":"William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom."},{"name":"Centre for Genomic Health, Life Sciences, Queen Mary University of London, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiola","family":"Del Greco M.","sequence":"additional","affiliation":[{"name":"Institute for Biomedicine, Eurac Research, Affiliated Institute of the University of Lubeck, Bolzano, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosalie B.T.M.","family":"Sterenborg","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Academic Center for Thyroid Diseases, Erasmus Medical Center, Rotterdam, The Netherlands."},{"name":"Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands."},{"name":"Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Layal","family":"Chaker","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Academic Center for Thyroid Diseases, Erasmus Medical Center, Rotterdam, The Netherlands."},{"name":"Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin P.","family":"Peeters","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Academic Center for Thyroid Diseases, Erasmus Medical Center, Rotterdam, The Netherlands."},{"name":"Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomasz","family":"Bednarczuk","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Endocrinology, Medical University of Warsaw, Warsaw, Poland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3837-2101","authenticated-orcid":false,"given":"Bj\u00f8rn O.","family":"\u00c5svold","sequence":"additional","affiliation":[{"name":"K.G. Jebsen Center for Genetic Epidemiology, NTNU, Norwegian University of Science and Technology, Trondheim, Norway."},{"name":"Department of Endocrinology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Burgess","sequence":"additional","affiliation":[{"name":"MRC Biostatistics Unit, Cambridge Institute of Public Health, University of Cambridge, Cambridge, United Kingdom."},{"name":"Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panos","family":"Deloukas","sequence":"additional","affiliation":[{"name":"William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom."},{"name":"Centre for Genomic Health, Life Sciences, Queen Mary University of London, London, United Kingdom."},{"name":"Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah, Saudi Arabia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8309-094X","authenticated-orcid":false,"given":"Alexander","family":"Teumer","sequence":"additional","affiliation":[{"name":"Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany."},{"name":"DZHK (German Center for Cardiovascular Research), Partner Site Greifswald, Greifswald, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3088-4375","authenticated-orcid":false,"given":"Christina","family":"Ellervik","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Boston Children's Hospital, Boston, Massachusetts, USA."},{"name":"Department of Pathology, Harvard Medical School, Boston, Massachusetts, USA."},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Medici","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Academic Center for Thyroid Diseases, Erasmus Medical Center, Rotterdam, The Netherlands."},{"name":"Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands."},{"name":"Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2021,8,3]]},"reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1996.03540040037030"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.62.6.593"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)32279-7"},{"key":"e_1_3_6_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07455"},{"key":"e_1_3_6_6_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-clinpsy-033109-132040"},{"key":"e_1_3_6_7_2","first-page":"205","article-title":"The thyroid axis and mood disorders: overview and future prospects","volume":"33","author":"Esposito S","year":"1997","unstructured":"Esposito S, , Prange AJJr, ., Golden RN. 1997. 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