{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T07:51:14Z","timestamp":1777881074822,"version":"3.51.4"},"reference-count":44,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82174479"],"award-info":[{"award-number":["82174479"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Sage Open Medicine"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>Rheumatoid arthritis (RA) and major depressive disorder (MDD) are interconnected conditions with a growing incidence, yet the mechanism that links them remains uncertain. This research focused on identifying the overlapping genes and pathogenic processes of RA and MDD via bioinformatics and National Health and Nutrition Examination Survey (NHANES) validation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      The Gene Expression Omnibus (GEO) database provided RA and MDD-related data from datasets GSE715573 and GSE76826. To identify common differentially expressed genes (co-DEGs) between RA and MDD, a differential analysis was carried out with |logFC|\u2009&gt;\u20090.5 and\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009&lt;\u20090.05 as the screening thresholds. GEO 2R was used to screen the differential genes applied to construct volcano diagrams; Genome Ontology and Kyoto Encyclopedia of Genes and Genomes, and Database for Annotation, Visualization, and Integration Discovery were used to explore the functions and regulatory pathways of co-DEGs. In addition, we examined data from the NHANES between 2005 and 2006 to verify the link between Hcy and depression symptoms in arthritis patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Differential gene expression analysis identified 142 downregulated and 102 upregulated genes in RA peripheral blood, 935 upregulated genes, and 409 downregulated genes in MDD peripheral blood. Ten common genes (VNN1, CKAP4, CLEC4D, F5, CBS, TNFRSF25, NELL2, RNASE2, TXN, and SRPK1) were identified, and abnormal biosynthesis and catabolism process of cysteine was found as a comorbid link between RA and MDD. Population-level NHANES analysis confirmed higher serum Hcy associated with more severe depression symptoms in arthritis patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>This investigation reveals the overlapping genetic signatures that explain the common manifestations and the association between RA and MDD. The two diseases share DEGs of CBS, VNN1, and TXN, which indicates that the abnormal metabolic pathway of homocysteine is a common pathogenic pathway in RA and MDD. NHANES proved an association between Hcy and depression in arthritis participants, indicating that Hcy may be an important biomarker for intervention to delay or ultimately prevent comorbidities, and highlights the importance of dietary interventions such as supplementing folate. The knowledge may help develop novel therapies and a potential strategy to prevent or delay the coexistence of depression and arthritis, especially RA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/20503121251410051","type":"journal-article","created":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T10:34:02Z","timestamp":1770806042000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Homocysteine as a biomarker in arthritis and depression: Evidence from NHANES and gene expression studies"],"prefix":"10.1177","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8353-9700","authenticated-orcid":false,"given":"Chuyu","family":"Deng","sequence":"first","affiliation":[{"name":"Department of Chinese Medicine, Jinan University First Affiliated Hospital, Guangzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenhua","family":"He","sequence":"additional","affiliation":[{"name":"Pediatric Neurosurgery Department, Guangdong-Women and Children Hospital, Guangzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaofeng","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Chinese Medicine, Jinan University First Affiliated Hospital, Guangzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2026,2,11]]},"reference":[{"issue":"3","key":"e_1_3_2_2_2","article-title":"Correlation of depression and anxiety with rheumatoid arthritis","volume":"14","author":"Jones Amaowei EE","year":"2022","unstructured":"Jones Amaowei EE, Anwar S, Kavanoor Sridhar K, et al. Correlation of depression and anxiety with rheumatoid arthritis. Cureus 2022; 14(3): e23137.","journal-title":"Cureus"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.3109\/s10165-012-0643-8"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12991-020-00322-2"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1007624"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0041-1742137"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.2147\/PRBM.S352984"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1004965"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.23148"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.4035"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40263-012-0028-8"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0217412"},{"issue":"6","key":"e_1_3_2_13_2","first-page":"904","article-title":"Major depressive episodes are associated with poor concordance with therapy in rheumatoid arthritis patients: the impact on disease outcomes","volume":"32","author":"Cabrera-Marroqu\u00edn R","year":"2014","unstructured":"Cabrera-Marroqu\u00edn R, Contreras-Y\u00e1\u00f1ez I, Alcocer-Castillejos N, et al. Major depressive episodes are associated with poor concordance with therapy in rheumatoid arthritis patients: the impact on disease outcomes. Clin Exp Rheumatol 2014; 32(6): 904\u2013913.","journal-title":"Clin Exp Rheumatol"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep20647"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2019-033958"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11920-008-0042-1"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyg.2020.542444"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/1926661"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.2147\/IJGM.S353487"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.18632\/aging.204030"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2022.844422"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2003-4-5-p3"},{"issue":"4","key":"e_1_3_2_23_2","first-page":"387","article-title":"Homocysteine enhances cytokine production in cultured synoviocytes from rheumatoid arthritis patients","volume":"24","author":"Lazzerini PE","year":"2006","unstructured":"Lazzerini PE, Selvi E, Lorenzini S, et al. Homocysteine enhances cytokine production in cultured synoviocytes from rheumatoid arthritis patients. Clin Exp Rheumatol 2006; 24(4): 387\u2013393.","journal-title":"Clin Exp Rheumatol"},{"issue":"2","key":"e_1_3_2_24_2","first-page":"190","article-title":"Vitamin status as predictors in rheumatoid arthritis","volume":"47","author":"Mititelu RR","year":"2021","unstructured":"Mititelu RR, Bacanoiu MV, Buga AM, et al. Vitamin status as predictors in rheumatoid arthritis. Curr Health Sci J 2021; 47(2): 190\u2013195.","journal-title":"Curr Health Sci J"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00393-021-01092-2"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-020-05093-5"},{"issue":"5","key":"e_1_3_2_27_2","first-page":"822","article-title":"Atherothrombotic events in rheumatoid arthritis are predicted by homocysteine \u2013 a six-year follow-up study","volume":"27","author":"Berglund S","year":"2009","unstructured":"Berglund S, S\u00f6dergren A, W\u00e5llberg Jonsson S, et al. Atherothrombotic events in rheumatoid arthritis are predicted by homocysteine \u2013 a six-year follow-up study. Clin Exp Rheumatol 2009; 27(5): 822\u2013825.","journal-title":"Clin Exp Rheumatol"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.5114\/reum.2020.99732"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2215-0366(18)30255-4"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2017.04.026"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2018.01.010"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2020.102470"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1055\/a-2460-7718"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2022.841429"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2022.931560"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2020.08.022"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2025.1599716"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-023-03377-w"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1080\/1028415X.2022.2060642"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.5c00568"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1111\/cpr.13322"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26020746"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2022.109149"},{"issue":"1","key":"e_1_3_2_44_2","first-page":"7","article-title":"The methionine-homocysteine cycle and its effects on cognitive diseases","volume":"8","author":"Miller AL.","year":"2003","unstructured":"Miller AL. The methionine-homocysteine cycle and its effects on cognitive diseases. Altern Med Rev 2003; 8(1): 7\u201319.","journal-title":"Altern Med Rev"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-nutr-071715-050947"}],"container-title":["Sage Open Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/20503121251410051","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/20503121251410051","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/20503121251410051","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:31:38Z","timestamp":1777595498000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/20503121251410051"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2]]},"references-count":44,"alternative-id":["10.1177\/20503121251410051"],"URL":"https:\/\/doi.org\/10.1177\/20503121251410051","relation":{},"ISSN":["2050-3121","2050-3121"],"issn-type":[{"value":"2050-3121","type":"print"},{"value":"2050-3121","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2]]},"article-number":"20503121251410051"}}