{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T13:01:26Z","timestamp":1790600486189,"version":"4.1.0"},"reference-count":21,"publisher":"Cambridge University Press (CUP)","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"unspecified","delay-in-days":270,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82501828"],"award-info":[{"award-number":["82501828"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82330042"],"award-info":[{"award-number":["82330042"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004826","name":"Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","award":["7254462"],"award-info":[{"award-number":["7254462"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016073","name":"Key Technologies Research and Development Program of Anhui Province","doi-asserted-by":"publisher","award":["2023YFE0119400"],"award-info":[{"award-number":["2023YFE0119400"]}],"id":[{"id":"10.13039\/100016073","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017549","name":"Science and Technology Innovation 2025 Major Project of Ningbo Municipality","doi-asserted-by":"publisher","award":["2021ZD0200702"],"award-info":[{"award-number":["2021ZD0200702"]}],"id":[{"id":"10.13039\/501100017549","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005090","name":"Beijing Nova Program","doi-asserted-by":"publisher","award":["202604841254"],"award-info":[{"award-number":["202604841254"]}],"id":[{"id":"10.13039\/501100005090","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005090","name":"Beijing Nova Program","doi-asserted-by":"publisher","award":["20230484425"],"award-info":[{"award-number":["20230484425"]}],"id":[{"id":"10.13039\/501100005090","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cambridge.org"],"crossmark-restriction":true},"short-container-title":["Psychol. Med."],"published-print":{"date-parts":[[2026]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"S0033291726105509_sec1\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Major depressive disorder (MDD) is a complex disorder caused by genetic and environmental factors. Previous evidence implicates a potential depression subtype from interaction between childhood maltreatment (CM) and kynurenine pathway (KP) gene. Here, we investigated the top-down multi-omics KP alterations for this subtype.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0033291726105509_sec2\" sec-type=\"methods\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A total of 142 patients with MDD receiving monotherapy were included. Individuals carrying\n                      <jats:italic>IDO2<\/jats:italic>\n                      rs2340953 TT genotype and reporting CM were classified as\n                      <jats:italic>IDO2-CM<\/jats:italic>\n                      group, whereas the remaining patients were categorized as\n                      <jats:italic>non-IDO2-CM<\/jats:italic>\n                      group. Plasma KP metabolites, DNA methylation, KP-related protein, and inflammatory protein were profiled. Group differences were examined using regression models adjusting for relevant covariates.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0033291726105509_sec3\" sec-type=\"results\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Thirty patients met criteria for the\n                      <jats:italic>IDO2-CM<\/jats:italic>\n                      group. Compared with\n                      <jats:italic>non-IDO2-CM<\/jats:italic>\n                      ,\n                      <jats:italic>IDO2-CM<\/jats:italic>\n                      individuals exhibited significantly poorer response rate to antidepressant at weeks 4 and 8. Metabolite analyses revealed a significantly elevated quinolinic acid (QA)\/kynurenine (KYN) ratio and QA\/kynurenic acid (KYNA) ratio in\n                      <jats:italic>IDO2-CM<\/jats:italic>\n                      group (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u00a0=\u00a00.086,\n                      <jats:italic>SE<\/jats:italic>\n                      \u00a0=\u00a00.042,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.023;\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u00a0=\u00a00.164,\n                      <jats:italic>SE<\/jats:italic>\n                      \u00a0=\u00a00.045,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.0006). Epigenetic analyses of KP genes demonstrated coordinated methylation shifts favoring QA production (hypomethylation of\n                      <jats:italic>KMO<\/jats:italic>\n                      and\n                      <jats:italic>AFMID<\/jats:italic>\n                      ; hypermethylation of\n                      <jats:italic>ACMSD<\/jats:italic>\n                      ) and suppression of KYNA related enzymes (hypermethylation of\n                      <jats:italic>CCBL1<\/jats:italic>\n                      ,\n                      <jats:italic>CCBL2<\/jats:italic>\n                      ,\n                      <jats:italic>AADAT<\/jats:italic>\n                      , and\n                      <jats:italic>GOT2<\/jats:italic>\n                      ). Proteomic profiling identified reduced circulating levels of KYNU and VCAM1 in\n                      <jats:italic>IDO2-CM<\/jats:italic>\n                      group.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0033291726105509_sec4\" sec-type=\"conclusions\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      CM interacting with\n                      <jats:italic>IDO2<\/jats:italic>\n                      genotype defines a biologically distinct MDD subtype characterized by poor antidepressant response and convergent multi-omics evidence of KP bias toward neurotoxic metabolism. These findings support a stratification strategy and highlight the KP as a potential target for precision treatment in depression.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1017\/s0033291726105509","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T12:43:24Z","timestamp":1790599404000},"update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":0,"title":["A kynurenine immune-metabolic subtype of depression defined by childhood maltreatment and IDO2: Evidence from multi-omics profiling"],"prefix":"10.1017","volume":"56","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8096-3568","authenticated-orcid":false,"given":"Yaoyao","family":"Sun","sequence":"first","affiliation":[{"name":"National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5074-2734","authenticated-orcid":false,"given":"Menghan","family":"Su","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital)"},{"name":"Jining Medical University"},{"name":"Shandong University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhewei","family":"Kang","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guorui","family":"Zhao","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueying","family":"Bai","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Xinxiang Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Guo","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueqi","family":"Wang","sequence":"additional","affiliation":[{"name":"Peking University School of Nursing"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Lu","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuyanan","family":"Zhang","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyang","family":"Feng","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junyuan","family":"Sun","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1201-8465","authenticated-orcid":false,"given":"Weihua","family":"Yue","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital)"},{"name":"Peking University"},{"name":"Peking University"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"56","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"key":"S0033291726105509_r4","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf9794"},{"key":"S0033291726105509_r10","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mp.4002006"},{"key":"S0033291726105509_r11","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2016.01.019"},{"key":"S0033291726105509_r6","doi-asserted-by":"publisher","DOI":"10.1126\/science.aab2358"},{"key":"S0033291726105509_r17","doi-asserted-by":"publisher","DOI":"10.1097\/PSY.0b013e318268de9f"},{"key":"S0033291726105509_r14","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-019-0414-4"},{"key":"S0033291726105509_r16","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-8-94"},{"key":"S0033291726105509_r1","doi-asserted-by":"publisher","DOI":"10.5498\/wjp.v13.i4.141"},{"key":"S0033291726105509_r3","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2021.05.018"},{"key":"S0033291726105509_r5","doi-asserted-by":"publisher","DOI":"10.1177\/0269881111434622"},{"key":"S0033291726105509_r2","first-page":"340","article-title":"Validity 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Published by Cambridge University Press","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 (http:\/\/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":"e300"}}