{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T05:42:40Z","timestamp":1793079760740,"version":"4.5.0"},"reference-count":58,"publisher":"Royal College of Psychiatrists","license":[{"start":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:00:00Z","timestamp":1792454400000},"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":["Br J Psychiatry"],"abstract":"<jats:sec id=\"S0007125026107983_as1\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Although commonly accepted depressive subtypes reflect phenotypic differences, there has been minimal progress in identification of discrete pathophysiological pathways, biomarkers or differential therapeutic approaches to effectively guide clinical management.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0007125026107983_as2\">\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To test the biological validity and clinical utility of a circadian subtype of depression on the basis of clinical course, differential medication response (self-reported) and genetic risk profile.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0007125026107983_as3\">\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>Cross-sectional data were drawn from the nationwide Australian Genetics of Depression Study. Participants were classified as having a \u2018circadian\u2019 or \u2018non-circadian\u2019 subtype of depression on the basis of meeting criteria for at least three binary circadian-associated features: social jetlag, seasonality, delayed sleep midpoint, evening chronotype, morning tiredness and hypersomnia. Clinical course characteristics were compared. Associations with response to commonly prescribed antidepressants and polygenic risk scores for mental disorders and sleep, circadian, metabolic and inflammatory traits were investigated using logistic regression models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0007125026107983_as4\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 2604 participants (23%; 80% female; mean age 37.87 \u00b1 13.62 years) had a circadian subtype. They reported an earlier age at onset (\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.001), more severe clinical features including (hypo)manic-like and psychotic-like experiences, suicidality, psychological distress and somatic complaints (all\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.001), weight gain during depressive episodes (\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.001), poorer response to selective serotonin reuptake inhibitors (odds ratio 0.88 [95% CI 0.82, 0.94]) and serotonin\u2013noradrenaline reuptake inhibitors (odds ratio 0.89 [95% CI 0.83, 0.97]), and more side-effects compared with those with a non-circadian subtype. Having a circadian subtype was associated with higher polygenic risk scores for attention-deficit hyperactivity disorder (odds ratio 1.11 [95% CI 1.06, 1.17]), major depression (odds ratio 1.11 [95% CI 1.06, 1.16]), anxiety (odds ratio 1.10 [95% CI 1.04, 1.15]), bipolar disorder (odds ratio 1.09 [95% CI 1.04, 1.14]), body mass index (odds ratio 1.09 [95% CI 1.05, 1.14]), triglycerides (odds ratio 1.10 [95% CI 1.06, 1.16]), interleukin-6 (odds ratio 1.08 [95% CI 1.03, 1.13]), higher insulin resistance (odds ratio 1.08 [95% CI 1.04, 1.13]), later sleep midpoint (odds ratio 1.15 [95% CI 1.10, 1.21]), insomnia (odds ratio 1.08 [95% CI 1.03, 1.13]) and later chronotype (odds ratio 0.68 [95% CI 0.65, 0.71]).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0007125026107983_as5\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings support the face validity and potential clinical utility of a circadian subtype of depression as a clinical profile. Pending independent replication, investigation of its biology and predictive utility are warranted.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1192\/bjp.2026.10798","type":"journal-article","created":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T23:06:17Z","timestamp":1792537577000},"page":"1-10","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":2,"title":["Clinical and genetic correlates of a circadian subtype of depression in the Australian Genetics of Depression Study"],"prefix":"10.1192","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8582-0491","authenticated-orcid":false,"given":"Emiliana","family":"Tonini","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0384j8v12","id-type":"ROR","asserted-by":"publisher"}],"name":"The University of Sydney"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3805-2936","authenticated-orcid":false,"given":"Jacob J.","family":"Crouse","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0384j8v12","id-type":"ROR","asserted-by":"publisher"}],"name":"The University of Sydney"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1648-341X","authenticated-orcid":false,"given":"Mirim","family":"Shin","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0384j8v12","id-type":"ROR","asserted-by":"publisher"}],"name":"The University of Sydney"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne S.","family":"Carpenter","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0384j8v12","id-type":"ROR","asserted-by":"publisher"}],"name":"The University of Sydney"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brittany L.","family":"Mitchell","sequence":"additional","affiliation":[{"name":"QIMR Berghofer Medical Research Institute"},{"name":"The University of Queensland"},{"name":"Queensland University of Technology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enda M.","family":"Byrne","sequence":"additional","affiliation":[{"name":"The University of Queensland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Penelope A.","family":"Lind","sequence":"additional","affiliation":[{"name":"QIMR Berghofer Medical Research Institute"},{"name":"The University of Queensland"},{"name":"Queensland University of Technology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott D.","family":"Gordon","sequence":"additional","affiliation":[{"name":"QIMR Berghofer Medical Research Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Parker","sequence":"additional","affiliation":[{"name":"QIMR Berghofer Medical Research Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel J.","family":"Hockey","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0384j8v12","id-type":"ROR","asserted-by":"publisher"}],"name":"The University of Sydney"},{"name":"The University of Sydney"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"To","sequence":"additional","affiliation":[{"name":"The University of Sydney"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Shim","sequence":"additional","affiliation":[{"name":"The University of Sydney"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Hill","sequence":"additional","affiliation":[{"name":"The University of Sydney"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Treneman","sequence":"additional","affiliation":[{"name":"The University of Sydney"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Scott","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0384j8v12","id-type":"ROR","asserted-by":"publisher"}],"name":"The University of Sydney"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7203-8601","authenticated-orcid":false,"given":"Jan","family":"Scott","sequence":"additional","affiliation":[{"name":"Newcastle University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen R.","family":"Merikangas","sequence":"additional","affiliation":[{"name":"National Institute of Mental Health"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi R.","family":"Wray","sequence":"additional","affiliation":[{"name":"The University of Queensland"},{"name":"University of Oxford"},{"name":"University of Oxford"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas G.","family":"Martin","sequence":"additional","affiliation":[{"name":"QIMR Berghofer Medical Research Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah E.","family":"Medland","sequence":"additional","affiliation":[{"name":"QIMR Berghofer Medical Research Institute"},{"name":"The University of Queensland"},{"name":"Queensland University of Technology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian B.","family":"Hickie","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0384j8v12","id-type":"ROR","asserted-by":"publisher"}],"name":"The University of Sydney"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"170","published-online":{"date-parts":[[2026,10,20]]},"reference":[{"key":"S0007125026107983_ref9","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaac.2020.12.035"},{"key":"S0007125026107983_ref13","doi-asserted-by":"publisher","DOI":"10.1111\/jsr.14307"},{"key":"S0007125026107983_ref3","volume-title":"Depression in Adults: Treatment and Management","year":"2022"},{"key":"S0007125026107983_ref48","doi-asserted-by":"publisher","DOI":"10.1002\/wps.21110"},{"key":"S0007125026107983_ref2","doi-asserted-by":"publisher","DOI":"10.1177\/0004867420979353"},{"key":"S0007125026107983_ref4","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2022-063095"},{"key":"S0007125026107983_ref45","doi-asserted-by":"publisher","DOI":"10.1016\/j.psychres.2005.07.012"},{"key":"S0007125026107983_ref42","doi-asserted-by":"publisher","DOI":"10.1111\/pedi.13003"},{"key":"S0007125026107983_ref23","doi-asserted-by":"publisher","DOI":"10.3109\/07420528.2013.784770"},{"key":"S0007125026107983_ref58","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpsgos.2024.100445"},{"key":"S0007125026107983_ref7","doi-asserted-by":"publisher","DOI":"10.1016\/j.smrv.2024.102022"},{"key":"S0007125026107983_ref27","doi-asserted-by":"publisher","DOI":"10.1177\/07487304251349408"},{"key":"S0007125026107983_ref24","first-page":"97","article-title":"A self-assessment questionnaire to determine morningness-eveningness in human circadian rhythms","volume":"4","author":"Horne","year":"1976","journal-title":"Int J Chronobiol"},{"key":"S0007125026107983_ref18","first-page":"72","article-title":"Seasonal pattern assessment questionnaire","volume":"41","author":"Rosenthal","year":"1984","journal-title":"J Affect Disord"},{"key":"S0007125026107983_ref29","doi-asserted-by":"publisher","DOI":"10.1186\/s13742-015-0047-8"},{"key":"S0007125026107983_ref56","doi-asserted-by":"publisher","DOI":"10.1016\/S2215-0366(21)00034-1"},{"key":"S0007125026107983_ref43","doi-asserted-by":"publisher","DOI":"10.1080\/09291016.2025.2480148"},{"key":"S0007125026107983_ref19","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1001\/archpsyc.1989.01810090065010","article-title":"Epidemiological findings of seasonal changes in mood and behavior: a telephone survey of Montgomery County","volume":"46","author":"Kasper","year":"1989","journal-title":"Maryland Arch Gen Psychiatry"},{"key":"S0007125026107983_ref46","doi-asserted-by":"publisher","DOI":"10.1016\/j.lanepe.2024.101166"},{"key":"S0007125026107983_ref28","doi-asserted-by":"publisher","DOI":"10.1086\/519795"},{"key":"S0007125026107983_ref22","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2021.0959"},{"key":"S0007125026107983_ref10","doi-asserted-by":"publisher","DOI":"10.1177\/07487304251328501"},{"key":"S0007125026107983_ref38","doi-asserted-by":"publisher","DOI":"10.1111\/bdi.13165"},{"key":"S0007125026107983_ref17","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2025.05.005"},{"key":"S0007125026107983_ref31","doi-asserted-by":"publisher","DOI":"10.1038\/ng1847"},{"key":"S0007125026107983_ref1","doi-asserted-by":"publisher","DOI":"10.1002\/wps.20461"},{"key":"S0007125026107983_ref14","doi-asserted-by":"publisher","DOI":"10.1016\/j.euroneuro.2011.07.007"},{"key":"S0007125026107983_ref44","doi-asserted-by":"publisher","DOI":"10.1002\/oby.23666"},{"key":"S0007125026107983_ref41","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2022.853096"},{"key":"S0007125026107983_ref47","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-021-00368-1"},{"key":"S0007125026107983_ref49","doi-asserted-by":"publisher","DOI":"10.1111\/pcn.13729"},{"key":"S0007125026107983_ref6","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2021.02.045"},{"key":"S0007125026107983_ref33","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2026.01.003"},{"key":"S0007125026107983_ref53","doi-asserted-by":"publisher","DOI":"10.1097\/JXX.0000000000000499"},{"key":"S0007125026107983_ref34","doi-asserted-by":"publisher","DOI":"10.1007\/s12402-016-0214-5"},{"key":"S0007125026107983_ref36","doi-asserted-by":"publisher","DOI":"10.1016\/j.psycom.2024.100188"},{"key":"S0007125026107983_ref40","doi-asserted-by":"publisher","DOI":"10.1080\/07420528.2021.1917594"},{"key":"S0007125026107983_ref39","doi-asserted-by":"publisher","DOI":"10.1111\/bdi.13304"},{"key":"S0007125026107983_ref35","doi-asserted-by":"publisher","DOI":"10.1080\/15622975.2018.1523565"},{"key":"S0007125026107983_ref52","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2020.00500"},{"key":"S0007125026107983_ref16","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2019-032580"},{"key":"S0007125026107983_ref12","doi-asserted-by":"publisher","DOI":"10.1111\/gbb.12569"},{"key":"S0007125026107983_ref5","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.2024.81"},{"key":"S0007125026107983_ref57","doi-asserted-by":"publisher","DOI":"10.1007\/978-981-95-6872-7_24"},{"key":"S0007125026107983_ref32","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-024-01704-y"},{"key":"S0007125026107983_ref26","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpsychires.2017.07.007"},{"key":"S0007125026107983_ref15","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2023.12.023"},{"key":"S0007125026107983_ref8","doi-asserted-by":"publisher","DOI":"10.1080\/07420528.2017.1332071"},{"key":"S0007125026107983_ref30","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03205-y"},{"key":"S0007125026107983_ref21","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-023-00851-2"},{"key":"S0007125026107983_ref50","doi-asserted-by":"publisher","DOI":"10.1186\/s40345-018-0133-9"},{"key":"S0007125026107983_ref55","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2019.2360"},{"key":"S0007125026107983_ref51","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.13r08634"},{"key":"S0007125026107983_ref54","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2021.110285"},{"key":"S0007125026107983_ref37","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2021.10.021"},{"key":"S0007125026107983_ref11","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpsychires.2025.03.003"},{"key":"S0007125026107983_ref20","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09576-1"},{"key":"S0007125026107983_ref25","doi-asserted-by":"publisher","DOI":"10.1007\/s40675-019-00154-x"}],"container-title":["The British Journal of Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cambridge.org\/core\/services\/aop-cambridge-core\/content\/view\/S0007125026107983","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T23:06:20Z","timestamp":1792537580000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cambridge.org\/core\/product\/identifier\/S0007125026107983\/type\/journal_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,20]]},"references-count":58,"alternative-id":["S0007125026107983"],"URL":"https:\/\/doi.org\/10.1192\/bjp.2026.10798","relation":{},"ISSN":["0007-1250","1472-1465"],"issn-type":[{"value":"0007-1250","type":"print"},{"value":"1472-1465","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,20]]},"assertion":[{"value":"\u00a9 The Author(s), 2026. Published by Cambridge University Press on behalf of Royal College of Psychiatrists","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"}]}}