{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T17:57:50Z","timestamp":1770141470436,"version":"3.49.0"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,8,2]],"date-time":"2022-08-02T00:00:00Z","timestamp":1659398400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003243","name":"Ministerstvo Zdravotnictv\u00ed Cesk\u00e9 Republiky","doi-asserted-by":"publisher","award":["FNBr, 65269705"],"award-info":[{"award-number":["FNBr, 65269705"]}],"id":[{"id":"10.13039\/501100003243","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001823","name":"Ministerstvo \u0160kolstv\u00ed, Ml\u00e1de\u017ee a Telov\u00fdchovy","doi-asserted-by":"publisher","award":["02.1.01\/0.0\/0.0\/18_046\/0015975"],"award-info":[{"award-number":["02.1.01\/0.0\/0.0\/18_046\/0015975"]}],"id":[{"id":"10.13039\/501100001823","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001823","name":"Ministerstvo \u0160kolstv\u00ed, Ml\u00e1de\u017ee a Telov\u00fdchovy","doi-asserted-by":"publisher","award":["CETOCOEN PLUS CZ.02.1.01\/0.0\/0.0\/15_003\/0000469"],"award-info":[{"award-number":["CETOCOEN PLUS CZ.02.1.01\/0.0\/0.0\/15_003\/0000469"]}],"id":[{"id":"10.13039\/501100001823","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007601","name":"Horizon 2020","doi-asserted-by":"publisher","award":["CETOCOEN EXCELLENCE Teaming 2 857560"],"award-info":[{"award-number":["CETOCOEN EXCELLENCE Teaming 2 857560"]}],"id":[{"id":"10.13039\/501100007601","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018866","name":"RECETOX Pr\u00edrodovedeck\u00e9 Fakulty Masarykovy Univerzity","doi-asserted-by":"publisher","award":["LM2018121"],"award-info":[{"award-number":["LM2018121"]}],"id":[{"id":"10.13039\/501100018866","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Psychiatry"],"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>Osteocalcin is a protein secreted by osteoblasts with a versatile endocrine role. Several domains in which it plays a role\u2014stress response, monoamine synthesis, and cognitive functioning\u2014are implicated also in the pathophysiology of major depressive disorder. In search of possible objective biomarkers of depression, the aim of the study was to assess the relationship between osteocalcin and depressive symptoms during the treatment of depressive episode.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The study included female inpatients with at least moderate depressive episode. In these patients, depression severity was measured using the Montgomery-\u00c5sberg Depression Rating Scale (MADRS), and osteocalcin levels were assessed before the stabilization of antidepressive treatment and after 6 weeks. Relationships between osteocalcin levels and symptoms were analyzed with mixed-effect and linear models, taking into account age, menopausal status, and body mass index.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In 11 out of 13 enrolled inpatients, osteocalcin levels decreased during the first 6 weeks of treatment; this decrease was significant according to the mixed-effects model (<jats:italic>t<\/jats:italic> = \u22122.345, <jats:italic>p<\/jats:italic> = 0.019). According to the linear model, this decrease was significantly associated with reduction in depressive symptom severity (<jats:italic>t<\/jats:italic> = 2.673, <jats:italic>p<\/jats:italic> = 0.028). Osteocalcin was not associated with initial depressive symptom severity, and initial osteocalcin levels did not predict response to treatment. Limitations of the study include low sample size and inclusion of both pre- and postmenopausal women of various ages.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This preliminary study suggests that osteocalcin may be a candidate biomarker of antidepressive treatment response and that this topic warrants further investigation.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fpsyt.2022.893012","type":"journal-article","created":{"date-parts":[[2022,8,2]],"date-time":"2022-08-02T04:46:13Z","timestamp":1659415573000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Osteocalcin levels decrease during the treatment of an acute depressive episode"],"prefix":"10.3389","volume":"13","author":[{"given":"Elis","family":"Barte\u010dk\u016f","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jana","family":"Ho\u0159\u00ednkov\u00e1","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pavel","family":"K\u0159enek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alena","family":"Damborsk\u00e1","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Josef","family":"Tomandl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie","family":"Tomandlov\u00e1","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Ku\u010dera","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jana","family":"Fialov\u00e1 Ku\u010derov\u00e1","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie","family":"Bienertov\u00e1-Va\u0161k\u016f","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,8,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1016\/j.cell.2013.08.042","article-title":"Maternal and offspring pools of osteocalcin influence brain development and functions","volume":"155","author":"Oury","year":"2013","journal-title":"Cell"},{"key":"B2","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.jnim.2017.01.001","article-title":"Osteocalcin: the extra-skeletal role of a vitamin K-dependent protein in glucose metabolism","volume":"7","author":"O'Connor","year":"2017","journal-title":"J Nutr Intermediary Metabol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1016\/S8756-3282(02)00902-X","article-title":"Patterns of osteocalcin and bone specific alkaline phosphatase by age, gender, and race or ethnicity","volume":"31","author":"Gundberg","year":"2002","journal-title":"Bone"},{"key":"B4","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1186\/1472-6823-13-11","article-title":"Reference intervals for serum osteocalcin concentrations in adult men and women from the study of health in Pomerania","volume":"13","author":"Hannemann","year":"2013","journal-title":"BMC Endocr Disord"},{"key":"B5","doi-asserted-by":"publisher","first-page":"2227","DOI":"10.1589\/jpts.28.2227","article-title":"Effects of 12-week exercise training on osteocalcin, high-sensitivity C-reactive protein concentrations, and insulin resistance in elderly females with osteoporosis","volume":"28","author":"Ahn","year":"2016","journal-title":"J Phys Therapy Sci"},{"key":"B6","doi-asserted-by":"publisher","first-page":"686","DOI":"10.1111\/cen.12601","article-title":"The effects of aerobic exercise training on serum osteocalcin, adipocytokines and insulin resistance on obese young males","volume":"82","author":"Kim","year":"2015","journal-title":"Clin Endocrinol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.7860\/JCDR\/2015\/14857.6318","article-title":"Serum osteocalcin as a diagnostic biomarker for primary osteoporosis in women","author":"Singh","year":"2015","journal-title":"J Clin DiagnRes"},{"key":"B8","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1186\/s12891-019-2863-y","article-title":"A meta-analysis of serum osteocalcin level in postmenopausal osteoporotic women compared to controls","volume":"20","author":"Liu","year":"2019","journal-title":"BMC Musculoskeletal Disord"},{"key":"B9","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.bone.2015.05.046","article-title":"New insights into the biology of osteocalcin","volume":"82","author":"Zoch","year":"2016","journal-title":"Bone"},{"key":"B10","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1007\/s11657-020-00812-6","article-title":"Osteocalcin and measures of adiposity: a systematic review and meta-analysis of observational studies","volume":"15","author":"Liu","year":"2020","journal-title":"Arch Osteoporos"},{"key":"B11","doi-asserted-by":"publisher","first-page":"e56","DOI":"10.3346\/jkms.2021.36.e56","article-title":"Association between serum osteocalcin levels and metabolic syndrome according to the menopausal status of Korean women","volume":"36","author":"Moon","year":"2021","journal-title":"J Korean Med Sci"},{"key":"B12","doi-asserted-by":"publisher","first-page":"890","DOI":"10.1016\/j.cmet.2019.08.012","article-title":"Mediation of the acute stress response by the skeleton","volume":"30","author":"Berger","year":"2019","journal-title":"Cell Metab"},{"key":"B13","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1186\/s13041-019-0444-5","article-title":"Roles for osteocalcin in brain signalling: implications in cognition- and motor-related disorders","volume":"12","author":"Shan","year":"2019","journal-title":"Mol Brain"},{"key":"B14","doi-asserted-by":"publisher","first-page":"4847","DOI":"10.1007\/s12035-016-0032-y","article-title":"The neurobiology of depression: an integrated overview from biological theories to clinical evidence","volume":"54","author":"Ferrari","year":"2017","journal-title":"Mol Neurobiol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1176","DOI":"10.1056\/NEJM199610173351602","article-title":"Bone mineral density in women with depression","volume":"335","author":"Michelson","year":"1996","journal-title":"N Engl J Med"},{"key":"B16","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1111\/j.1742-1241.2006.01276.x","article-title":"Relation of cortisol levels and bone mineral density among premenopausal women with major depression","volume":"61","author":"Altindag","year":"2007","journal-title":"Int J Clin Pract"},{"key":"B17","doi-asserted-by":"publisher","first-page":"17134756","DOI":"10.3390\/ijerph17134756","article-title":"Bone metabolism in patients treated for depression","volume":"17","author":"Skowro\u0144ska-J\u00f3wiak","year":"2020","journal-title":"Int J Environ Res Public Health"},{"key":"B18","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1097\/00006842-200011000-00006","article-title":"Increased bone remodeling in first-episode major depressive disorder","volume":"62","author":"Herr\u00e1n","year":"2000","journal-title":"Psychosom Med"},{"key":"B19","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1176\/appi.ajp.162.1.168","article-title":"Bone mineral density, markers of bone turnover, and cytokines in young women with borderline personality disorder with and without comorbid major depressive disorder","volume":"162","author":"Kahl","year":"2005","journal-title":"Am J Psychiatry"},{"key":"B20","doi-asserted-by":"publisher","first-page":"e40894","DOI":"10.1371\/journal.pone.0040894","article-title":"Do premenopausal women with major depression have low bone mineral density? A 36-month prospective study","volume":"7","author":"Cizza","year":"2012","journal-title":"PLoS One"},{"key":"B21","doi-asserted-by":"publisher","first-page":"104878","DOI":"10.1016\/j.psyneuen.2020.104878","article-title":"Serum osteocalcin is associated with subjective stress in people with depression and type 2 diabetes","volume":"122","author":"Nguyen","year":"2020","journal-title":"Psychoneuroendocrinology"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1316","DOI":"10.1016\/j.jpsychires.2011.04.005","article-title":"Treatment of a major depression episode suppresses markers of bone turnover in premenopausal women","volume":"45","author":"Aydin","year":"2011","journal-title":"J Psychiatr Res"},{"key":"B23","volume-title":"Diagnostic and Statistical Manual of Mental Disorders: DSM-5","year":"2013"},{"key":"B24","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1192\/bjp.134.4.382","article-title":"a new depression scale designed to be sensitive to change","volume":"134","author":"Montgomery","year":"1979","journal-title":"Br J Psychiatry"},{"key":"B25","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1111\/j.1755-5949.2009.00102.x","article-title":"RESEARCH: validation of the massachusetts general hospital antidepressant treatment history questionnaire (ATRQ)","volume":"16","author":"Chandler","year":"2010","journal-title":"CNS Neurosci Therapeut"},{"key":"B26","doi-asserted-by":"publisher","first-page":"159","DOI":"10.4068\/cmj.2016.52.3.159","article-title":"Second generation antipsychotics in the treatment of major depressive disorder: an update","volume":"52","author":"Wang","year":"2016","journal-title":"Chonnam Med J"},{"key":"B27","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1037\/0033-2909.112.1.155","article-title":"A power primer","volume":"112","author":"Cohen","year":"1992","journal-title":"Psychol Bull"},{"key":"B28","volume-title":"R: A Language and Environment for Statistical Computing","year":"2021"},{"key":"B29","doi-asserted-by":"publisher","first-page":"142","DOI":"10.5603\/EP.a2018.0008","article-title":"Effects of physical activity on sclerostin concentrations","volume":"69","author":"Janik","year":"2018","journal-title":"Endokrynol Pol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.jpsychires.2016.02.022","article-title":"24-h activity rhythm and sleep in depressed outpatients","volume":"77","author":"Hori","year":"2016","journal-title":"J Psychiatr Res"},{"key":"B31","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/978-1-4615-5051-8_11","article-title":"Decreased serum concentration of osteocalcin after sunshine exposure","volume-title":"Biologic Effects of Light 1998: Proceedings of a Symposium Basel, Switzerland November 1\u20133. 1998","author":"Falkenbach","year":"1999"},{"key":"B32","doi-asserted-by":"publisher","first-page":"1170","DOI":"10.1038\/nm.4166","article-title":"Serotonin reuptake inhibitors act centrally to cause bone loss in mice by counteracting a local antiresorptive effect","volume":"22","author":"Ortu\u00f1o","year":"2016","journal-title":"Nat Med"},{"key":"B33","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1016\/j.schres.2016.06.034","article-title":"Relationship between long-term use of a typical antipsychotic medication by Chinese schizophrenia patients and the bone turnover markers serum osteocalcin and \u03b2-CrossLaps","volume":"176","author":"Zhang","year":"2016","journal-title":"Schizophr Res"},{"key":"B34","doi-asserted-by":"publisher","first-page":"456","DOI":"10.3389\/fphys.2016.00456","article-title":"Nerve growth factor, brain-derived neurotrophic factor and osteocalcin gene relationship in energy regulation, bone homeostasis and reproductive organs analyzed by mRNA quantitative evaluation and linear correlation analysis","volume":"7","author":"Camerino","year":"2016","journal-title":"Front Physiol"},{"key":"B35","doi-asserted-by":"publisher","first-page":"e0172270","DOI":"10.1371\/journal.pone.0172270","article-title":"Meta-analyses of comparative efficacy of antidepressant medications on peripheral BDNF concentration in patients with depression","volume":"12","author":"Zhou","year":"2017","journal-title":"PLoS One"},{"key":"B36","doi-asserted-by":"publisher","first-page":"974","DOI":"10.3389\/fpsyt.2019.00974","article-title":"Cortisol and major depressive disorder\u2013translating findings from humans to animal models and back","volume":"10","author":"Nandam","year":"2020","journal-title":"Front Psychiatry"}],"container-title":["Frontiers in Psychiatry"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpsyt.2022.893012\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,2]],"date-time":"2022-08-02T04:46:18Z","timestamp":1659415578000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpsyt.2022.893012\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,2]]},"references-count":36,"alternative-id":["10.3389\/fpsyt.2022.893012"],"URL":"https:\/\/doi.org\/10.3389\/fpsyt.2022.893012","relation":{},"ISSN":["1664-0640"],"issn-type":[{"value":"1664-0640","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,2]]},"article-number":"893012"}}