{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T05:04:12Z","timestamp":1781067852554,"version":"3.54.1"},"reference-count":57,"publisher":"Cambridge University Press (CUP)","license":[{"start":{"date-parts":[[2024,11,12]],"date-time":"2024-11-12T00:00:00Z","timestamp":1731369600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["cambridge.org"],"crossmark-restriction":true},"short-container-title":["Acta Neuropsychiatr."],"published-print":{"date-parts":[[2025]]},"abstract":"<jats:title>Abstract<\/jats:title>\n\t  <jats:sec id=\"S0924270824000437_as1\">\n\t    <jats:title>Objective:<\/jats:title>\n\t    <jats:p>Associations between leptin (<jats:italic>LEP<\/jats:italic>) and leptin receptor (<jats:italic>LEPR<\/jats:italic>) gene polymorphisms and mood disorders have been found but not yet confirmed in multiple studies. The aim of our study was to study the associations between <jats:italic>LEP<\/jats:italic> and <jats:italic>LEPR<\/jats:italic> single nucleotide polymorphisms (SNPs) and treatment response of depression. Associations between leptin levels and depression severity were also investigated.<\/jats:p>\n\t  <\/jats:sec>\n\t  <jats:sec id=\"S0924270824000437_as2\">\n\t    <jats:title>Methods:<\/jats:title>\n\t    <jats:p>The data included 242 depressed patients in secondary psychiatric care. Symptoms of depression were assessed with the Montgomery\u2013\u00c5sberg Depression Rating Scale (MADRS). Previously found <jats:italic>LEP<\/jats:italic> and <jats:italic>LEPR<\/jats:italic> SNPs associated with depression and other mood disorders were studied. Furthermore, all available <jats:italic>LEP<\/jats:italic> and <jats:italic>LEPR<\/jats:italic> SNPs were clumped using proxy SNPs to represent gene areas in <jats:italic>r<\/jats:italic><jats:sup>2<\/jats:sup> &gt; 0.2 linkage disequilibrium and their association with treatment response was analysed with logistic regression.<\/jats:p>\n\t  <\/jats:sec>\n\t  <jats:sec id=\"S0924270824000437_as3\">\n\t    <jats:title>Results:<\/jats:title>\n\t    <jats:p>Two proxy SNPs of <jats:italic>LEPR<\/jats:italic> gene, rs12564738 and rs12029311, were associated with MADRS response at 6 weeks (<jats:italic>p<\/jats:italic> adjusted = 0.024, <jats:italic>p<\/jats:italic> adjusted = 0.024). SNPs from previous studies were not associated with MADRS response, but <jats:italic>LEPR<\/jats:italic> rs12145690 from a previous study was strongly associated with rs12564738 (<jats:italic>r<\/jats:italic><jats:sup>2<\/jats:sup> = 0.94). The positive association between leptin levels and MADRS score at baseline after adjusting with age, sex, body mass index (BMI), Alcohol Use Disorders Identification Test score, and smoking was found (<jats:italic>p<\/jats:italic> = 0.011).<\/jats:p>\n\t  <\/jats:sec>\n\t  <jats:sec id=\"S0924270824000437_as4\">\n\t    <jats:title>Conclusion:<\/jats:title>\n\t    <jats:p>Our findings suggest that <jats:italic>LEPR<\/jats:italic> polymorphisms are associated with depression treatment response. We also found associations between leptin levels and depression independently of BMI. Further studies and meta-analyses are needed to confirm the significance of found SNPs and the role of leptin in depression.<\/jats:p>\n\t  <\/jats:sec>","DOI":"10.1017\/neu.2024.43","type":"journal-article","created":{"date-parts":[[2024,11,12]],"date-time":"2024-11-12T06:14:32Z","timestamp":1731392072000},"update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":2,"title":["Leptin and leptin receptor gene polymorphisms and depression treatment response"],"prefix":"10.1017","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-5519-8438","authenticated-orcid":false,"given":"Ida-Maria","family":"Tavast","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anssi","family":"Solismaa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo-Pekka","family":"Lyytik\u00e4inen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Mononen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eeva","family":"Moilanen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari","family":"H\u00e4m\u00e4l\u00e4inen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terho","family":"Lehtim\u00e4ki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6891-2266","authenticated-orcid":false,"given":"Olli","family":"Kampman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"56","published-online":{"date-parts":[[2024,11,12]]},"reference":[{"key":"S0924270824000437_ref1","doi-asserted-by":"publisher","DOI":"10.14712\/18059694.2021.27"},{"key":"S0924270824000437_ref11","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1111\/pcn.12922","article-title":"Correlations of serum leptin and leptin resistance with depression and anxiety in patients with type 2 diabetes","volume":"73","author":"Cernea","year":"2019","journal-title":"Psychiatry and Clinical Neurosciences"},{"key":"S0924270824000437_ref50","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23094713"},{"key":"S0924270824000437_ref10","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2021.05.008"},{"key":"S0924270824000437_ref47","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2023.1296764"},{"key":"S0924270824000437_ref8","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.jad.2018.05.008","article-title":"Leptin and adiponectin levels in major depressive disorder: A systematic review and meta-analysis","volume":"238","author":"Cao","year":"2018","journal-title":"Journal of Affective Disorders"},{"key":"S0924270824000437_ref30","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/978-981-13-1286-1_8","article-title":"The leptin resistance","volume":"1090","author":"Liu","year":"2018","journal-title":"Advances in Experimental Medicine and Biology"},{"key":"S0924270824000437_ref42","unstructured":"Ostrobothnia Depression Study (ODS) (2016) A naturalistic Follow-up Study on Depression and Related Substance Use Disorders. https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02520271. Accessed May 18, 2023."},{"key":"S0924270824000437_ref20","doi-asserted-by":"publisher","DOI":"10.1097\/MED.0000000000000184"},{"key":"S0924270824000437_ref53","doi-asserted-by":"crossref","first-page":"891325","DOI":"10.3389\/fpsyt.2022.891325","article-title":"Association between self-rating depression scores and total ghrelin and adipokine serum levels in a large population-based sample","volume":"13","author":"Wittekind","year":"2022","journal-title":"Frontiers in Psychiatry"},{"key":"S0924270824000437_ref49","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/0306-4603(86)90040-7","article-title":"The reliability of a timeline method for assessing normal drinker college students\u2019 recent drinking history: Utility for alcohol research","volume":"11","author":"Sobell","year":"1986","journal-title":"Addictive Behaviors"},{"key":"S0924270824000437_ref24","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1819.2005.01445.x"},{"key":"S0924270824000437_ref6","doi-asserted-by":"publisher","DOI":"10.1093\/alcalc\/agaa044"},{"key":"S0924270824000437_ref51","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.psychres.2018.11.075","article-title":"Plasma levels of leptin and adiponectin and depressive symptoms in young adults","volume":"272","author":"Syk","year":"2019","journal-title":"Psychiatry Research"},{"key":"S0924270824000437_ref35","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-018-0017-5"},{"key":"S0924270824000437_ref17","first-page":"22","article-title":"Leptin and psychiatric illnesses: Does leptin play a role in antipsychotic-induced weight gain? Lipids in health and disease","volume":"19","author":"Endomba","year":"2020","journal-title":"BioMed Central Ltd"},{"key":"S0924270824000437_ref31","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2007.10.010"},{"key":"S0924270824000437_ref55","doi-asserted-by":"publisher","DOI":"10.1080\/00048670601057759"},{"key":"S0924270824000437_ref25","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2005.09.015"},{"key":"S0924270824000437_ref21","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1017\/S0033291712001511","article-title":"Global variation in the prevalence and incidence of major depressive disorder: A systematic review of the epidemiological literature","volume":"43","author":"Ferrari","year":"2013","journal-title":"Psychological Medicine"},{"key":"S0924270824000437_ref27","doi-asserted-by":"publisher","DOI":"10.1016\/j.euroneuro.2012.08.010"},{"key":"S0924270824000437_ref7","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1207\/s15327752jpa6703_13","article-title":"Comparison of beck depression inventories -IA and -II in psychiatric outpatients","volume":"67","author":"Beck","year":"1996","journal-title":"Journal of Personality Assessment"},{"key":"S0924270824000437_ref36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.psyneuen.2013.12.015","article-title":"The association between leptin and depressive symptoms is modulated by abdominal adiposity","volume":"42","author":"Milaneschi","year":"2014","journal-title":"Psychoneuroendocrinology"},{"key":"S0924270824000437_ref29","doi-asserted-by":"publisher","DOI":"10.1007\/s00408-019-00254-z"},{"key":"S0924270824000437_ref32","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0508901103"},{"key":"S0924270824000437_ref33","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1016\/j.biopsych.2015.10.023","article-title":"Leptin dysregulation is specifically associated with major depression with atypical features: Evidence for a mechanism connecting obesity and depression","volume":"81","author":"Milaneschi","year":"2017","journal-title":"Biological Psychiatry"},{"key":"S0924270824000437_ref12","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23179635"},{"key":"S0924270824000437_ref9","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpsychires.2014.08.002"},{"key":"S0924270824000437_ref26","doi-asserted-by":"publisher","DOI":"10.1002\/da.20570"},{"key":"S0924270824000437_ref39","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2014.09.010"},{"key":"S0924270824000437_ref44","unstructured":"R Core Team (2021). R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. https:\/\/www.R-project.org\/. Accessed February 24, 2024."},{"key":"S0924270824000437_ref4","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1016\/S0140-6736(14)62254-6","article-title":"Transitioning health systems for multimorbidity","volume":"386","author":"Atun","year":"2015","journal-title":"The Lancet"},{"key":"S0924270824000437_ref3","doi-asserted-by":"publisher","DOI":"10.1016\/j.psychres.2018.03.073"},{"key":"S0924270824000437_ref40","first-page":"5","article-title":"Definitions of antidepressant treatment response, remission, nonresponse, partial response, and other relevant outcomes: A focus on treatment-resistant depression","volume":"62","author":"Nierenberg","year":"2001","journal-title":"The Journal of Clinical Psychiatry"},{"key":"S0924270824000437_ref2","doi-asserted-by":"publisher","DOI":"10.1080\/13651501.2019.1711422"},{"key":"S0924270824000437_ref34","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2017.3016"},{"key":"S0924270824000437_ref41","doi-asserted-by":"crossref","first-page":"2751","DOI":"10.3390\/nu11112751","article-title":"Candidate gene and genome-wide association studies for circulating leptin levels reveal population and sex-specific associations in high cardiovascular risk mediterranean subjects","volume":"11","author":"Ortega-Azor\u00edn","year":"2019","journal-title":"Nutrients"},{"key":"S0924270824000437_ref43","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/j.tins.2008.06.006","article-title":"The HPA axis in major depression: Classical theories and new developments","volume":"31","author":"Pariante","year":"2008","journal-title":"Trends in Neurosciences"},{"key":"S0924270824000437_ref52","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.jad.2018.09.014","article-title":"Higher plasma leptin and lower C-peptide levels are associated with depression: A cross-sectional study","volume":"243","author":"Takekawa","year":"2019","journal-title":"Journal of Affective Disorders"},{"key":"S0924270824000437_ref18","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2021.108877"},{"key":"S0924270824000437_ref16","doi-asserted-by":"publisher","DOI":"10.1080\/10503307.2023.2197630"},{"key":"S0924270824000437_ref14","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0028912"},{"key":"S0924270824000437_ref19","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2005.01.009"},{"key":"S0924270824000437_ref15","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199602013340503"},{"key":"S0924270824000437_ref23","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1038\/s41419-018-1129-1","article-title":"Leptin in depression: A potential therapeutic target","volume":"9","author":"Ge","year":"2018","journal-title":"Cell Death and Disease"},{"key":"S0924270824000437_ref5","unstructured":"Babor, T. F. , Higgins-Biddle, J. C. , Saunders, J. B. and Monteiro, M. G. (2001). The Alcohol Use Disorders Identification Test Guidelines for Use in Primary Care. World Health Organization, Department of Mental Health and Substance Dependence. http:\/\/apps.who.int\/iris\/bitstream\/10665\/67205\/1\/WHO_MSD_MSB_01.6a.pdf. Accessed February 23, 2024."},{"key":"S0924270824000437_ref37","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.134.4.382"},{"key":"S0924270824000437_ref57","doi-asserted-by":"crossref","first-page":"378","DOI":"10.3389\/fnins.2019.00378","article-title":"Role of leptin in mood disorder and neurodegenerative disease","volume":"13","author":"Zou","year":"2019","journal-title":"Frontiers in Neuroscience"},{"key":"S0924270824000437_ref46","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.ygcen.2012.01.009","article-title":"Leptin and the hypothalamo-pituitary-adrenal stress axis","volume":"177","author":"Roubos","year":"2012","journal-title":"General and Comparative Endocrinology"},{"key":"S0924270824000437_ref48","first-page":"22","article-title":"The mini-international neuropsychiatric interview (M.I.N.I.): The development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10","volume":"59","author":"Sheehan","year":"1998","journal-title":"The Journal of clinical psychiatry"},{"key":"S0924270824000437_ref22","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1038\/mp.2011.161","article-title":"Leptin restores adult hippocampal neurogenesis in a chronic unpredictable stress model of depression and reverses glucocorticoid-induced inhibition of GSK-3B2;\/B2;-catenin signaling","volume":"17","author":"Garza","year":"2012","journal-title":"Molecular Psychiatry"},{"key":"S0924270824000437_ref45","doi-asserted-by":"publisher","DOI":"10.1097\/YPG.0000000000000080"},{"key":"S0924270824000437_ref56","doi-asserted-by":"publisher","DOI":"10.1186\/s12944-017-0644-x"},{"key":"S0924270824000437_ref54","doi-asserted-by":"crossref","first-page":"2634","DOI":"10.1210\/en.2011-0004","article-title":"Impaired CNS leptin action is implicated in depression associated with obesity","volume":"152","author":"Yamada","year":"2011","journal-title":"Endocrinology"},{"key":"S0924270824000437_ref38","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1097\/PSY.0b013e31824f5de0","article-title":"The association between depression and leptin is mediated by adiposity","volume":"74","author":"Morris","year":"2012","journal-title":"Psychosomatic Medicine"},{"key":"S0924270824000437_ref13","doi-asserted-by":"publisher","DOI":"10.1007\/s12160-013-9479-5"},{"key":"S0924270824000437_ref28","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1159\/000054641","article-title":"Low leptin levels but normal body mass indices in patients with depression or schizophrenia","volume":"73","author":"Kraus","year":"2001","journal-title":"Neuroendocrinology"}],"container-title":["Acta Neuropsychiatrica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cambridge.org\/core\/services\/aop-cambridge-core\/content\/view\/S0924270824000437","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T12:05:34Z","timestamp":1742817934000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cambridge.org\/core\/product\/identifier\/S0924270824000437\/type\/journal_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,12]]},"references-count":57,"alternative-id":["S0924270824000437"],"URL":"https:\/\/doi.org\/10.1017\/neu.2024.43","relation":{},"ISSN":["0924-2708","1601-5215"],"issn-type":[{"value":"0924-2708","type":"print"},{"value":"1601-5215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,12]]},"assertion":[{"value":"\u00a9 The Author(s), 2024. Published by Cambridge University Press on behalf of Scandinavian College of Neuropsychopharmacology","name":"copyright","label":"Copyright","group":{"name":"copyright_and_licensing","label":"Copyright and Licensing"}},{"value":"This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (https:\/\/creativecommons.org\/licenses\/by\/4.0\/), which permits unrestricted re-use, distribution and reproduction, provided the original article is properly cited.","name":"license","label":"License","group":{"name":"copyright_and_licensing","label":"Copyright and Licensing"}},{"value":"This content has been made available to all.","name":"free","label":"Free to read"}],"article-number":"e38"}}