{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:03:40Z","timestamp":1785409420477,"version":"3.56.0"},"reference-count":107,"publisher":"Cambridge University Press (CUP)","license":[{"start":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:00:00Z","timestamp":1781740800000},"content-version":"unspecified","delay-in-days":168,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["142255, 180449, 186254"],"award-info":[{"award-number":["142255, 180449, 186254"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000194","name":"Nova Scotia Health Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000194","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000874","name":"Brain and Behavior Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000874","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=\"S0033291726104905_sec1\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Bipolar disorders (BD) rank among the most disabling conditions, affecting millions worldwide. Cognitive impairment in BD is linked with brain changes and worse functional outcomes. Obesity and metabolic syndrome (MetSy) are overrepresented in BD and are associated with more pronounced brain structural and cognitive alterations in the general population. Here, we studied for the first time the contribution of metabolic dysfunction to both brain and cognitive alterations in BD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0033291726104905_sec2\" sec-type=\"methods\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We recruited 163 participants (76 individuals with BD, 87 controls). We used principal component analysis (PCA) to derive a composite measure of metabolic health from WHR, BMI, HOMA-IR, HbA1c, TGC, HDL, LDL, systolic, diastolic BP, and to derive a composite cognitive measure from the California Verbal Learning Test and Digit Span. Brain structure was indexed using machine-learning-predicted BrainAGE derived from T1-weighted MRI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0033291726104905_sec3\" sec-type=\"results\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Obesity, hypertension, insulin resistance, and dyslipidemia contributed most strongly to variance in metabolic health in this sample. This MetSy-associated risk cluster predicted higher BrainAGE (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u00a0=\u00a00.75\u00a0\u00b1\u00a00.29,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.011) and lower cognitive performance (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u00a0=\u00a0\u22120.19\u00a0\u00b1\u00a00.09,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.037), accounting for 30% of the association between BD and higher BrainAGE and 25% of the association between BD and worse cognitive performance. These effects were independent of symptoms, medications, illness course, and duration.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0033291726104905_sec4\" sec-type=\"conclusions\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>MetSy, particularly obesity, was closely linked with brain\/cognitive impairments in BD. While the need for metabolic monitoring should be informed by the diagnosis of BD, screening for MetSy can also help track brain health and cognitive functioning.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1017\/s0033291726104905","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T08:43:20Z","timestamp":1781772200000},"update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":0,"title":["The role of metabolic health in neurostructural and cognitive alterations in bipolar disorders"],"prefix":"10.1017","volume":"56","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-1255-7936","authenticated-orcid":false,"given":"Maya","family":"Selitser","sequence":"first","affiliation":[{"name":"Dalhousie University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2029-810X","authenticated-orcid":false,"given":"Sean R.","family":"McWhinney","sequence":"additional","affiliation":[{"name":"Dalhousie University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linzhi","family":"Wu","sequence":"additional","affiliation":[{"name":"Dalhousie University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1360-8544","authenticated-orcid":false,"given":"Julia","family":"Fraiha-Pegado","sequence":"additional","affiliation":[{"name":"Dalhousie University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2906-9282","authenticated-orcid":false,"given":"Lorielle","family":"Dietze","sequence":"additional","affiliation":[{"name":"Dalhousie University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Corkum","sequence":"additional","affiliation":[{"name":"Dalhousie University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1013-7146","authenticated-orcid":false,"given":"Lena","family":"Selitser","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/008dmsy67","id-type":"ROR","asserted-by":"publisher"}],"name":"Adler School of Professional Psychology: Adler University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4955-9150","authenticated-orcid":false,"given":"Abraham","family":"Nunes","sequence":"additional","affiliation":[{"name":"Dalhousie University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9544-3944","authenticated-orcid":false,"given":"Martin","family":"Alda","sequence":"additional","affiliation":[{"name":"Dalhousie University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1859-5738","authenticated-orcid":false,"given":"Katja","family":"Franke","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/035rzkx15","id-type":"ROR","asserted-by":"publisher"}],"name":"Jena University Hospital: Universitatsklinikum Jena"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0281-8458","authenticated-orcid":false,"given":"Tomas","family":"Hajek","sequence":"additional","affiliation":[{"name":"Dalhousie University"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"56","published-online":{"date-parts":[[2026,6,18]]},"reference":[{"key":"S0033291726104905_r54","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2021.12.028"},{"key":"S0033291726104905_r23","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2013.07.022"},{"key":"S0033291726104905_r12","doi-asserted-by":"publisher","DOI":"10.1016\/j.euroneuro.2021.06.008"},{"key":"S0033291726104905_r50","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2016.08.018"},{"key":"S0033291726104905_r29","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0000000000003553"},{"key":"S0033291726104905_r32","doi-asserted-by":"publisher","DOI":"10.1021\/cn5000309"},{"key":"S0033291726104905_r62","doi-asserted-by":"publisher","DOI":"10.1093\/schbul\/sbt142"},{"key":"S0033291726104905_r73","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2009.07.003"},{"key":"S0033291726104905_r78","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2020.116696"},{"key":"S0033291726104905_r91","doi-asserted-by":"publisher","DOI":"10.2174\/1570159X13666150429002536"},{"key":"S0033291726104905_r72","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-5618.2007.00327.x"},{"key":"S0033291726104905_r13","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291714000439"},{"key":"S0033291726104905_r49","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2014.06.035"},{"key":"S0033291726104905_r113","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.133.5.429"},{"key":"S0033291726104905_r45","doi-asserted-by":"publisher","DOI":"10.1159\/000296071"},{"key":"S0033291726104905_r102","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2012.11.008"},{"key":"S0033291726104905_r20","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhad214"},{"key":"S0033291726104905_r93","doi-asserted-by":"publisher","DOI":"10.3389\/fnhum.2019.00290"},{"key":"S0033291726104905_r98","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr597"},{"key":"S0033291726104905_r100","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v059.i05"},{"key":"S0033291726104905_r110","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2017.11.020"},{"key":"S0033291726104905_r1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2021.09.008"},{"key":"S0033291726104905_r69","doi-asserted-by":"publisher","DOI":"10.1016\/j.mri.2025.110419"},{"key":"S0033291726104905_r21","first-page":"225","article-title":"Hypertension and cognitive dysfunction: A narrative review","volume":"40","author":"Cheon","year":"2023","journal-title":"Journal of Yeungnam Medical Science"},{"key":"S0033291726104905_r16","doi-asserted-by":"publisher","DOI":"10.2337\/dc10-0851"},{"key":"S0033291726104905_r55","doi-asserted-by":"publisher","DOI":"10.1111\/acps.13278"},{"key":"S0033291726104905_r8","first-page":"e72211","article-title":"Prevalence of metabolic syndrome and its association with clinical correlates and caregiver burden in patients with bipolar disorder at a tertiary hospital","volume":"16","author":"Antony","year":"2024","journal-title":"Cureus Journal of Medical Science"},{"key":"S0033291726104905_r22","doi-asserted-by":"publisher","DOI":"10.1186\/s40345-019-0142-3"},{"key":"S0033291726104905_r65","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcae336"},{"key":"S0033291726104905_r94","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2020.01.145"},{"key":"S0033291726104905_r75","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291723000223"},{"key":"S0033291726104905_r17","unstructured":"Centers for Disease Control and Prevention. (2024). Obesity and overweight. https:\/\/www.cdc.gov\/nchs\/fastats\/obesity-overweight.htm"},{"key":"S0033291726104905_r7","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.121.022107"},{"key":"S0033291726104905_r48","doi-asserted-by":"publisher","DOI":"10.2147\/NDT.S396424"},{"key":"S0033291726104905_r34","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2013.00090"},{"key":"S0033291726104905_r63","doi-asserted-by":"publisher","DOI":"10.1037\/a0016277"},{"key":"S0033291726104905_r97","doi-asserted-by":"publisher","DOI":"10.1503\/jpn.240105"},{"key":"S0033291726104905_r112","doi-asserted-by":"publisher","DOI":"10.1016\/j.eurpsy.2011.02.004"},{"key":"S0033291726104905_r40","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2006.01.003"},{"key":"S0033291726104905_r4","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-023-02501-7"},{"key":"S0033291726104905_r74","doi-asserted-by":"publisher","DOI":"10.1111\/bdi.13172"},{"key":"S0033291726104905_r18","unstructured":"Centers for Disease Control and Prevention. (2025a). High blood pressure facts. https:\/\/www.cdc.gov\/high-blood-pressure\/data-research\/facts-stats\/index.html"},{"key":"S0033291726104905_r109","doi-asserted-by":"publisher","DOI":"10.1016\/j.acn.2006.06.002"},{"key":"S0033291726104905_r6","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2021.04.090"},{"key":"S0033291726104905_r88","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.20870"},{"key":"S0033291726104905_r108","doi-asserted-by":"publisher","DOI":"10.1093\/ajh\/hpae077"},{"key":"S0033291726104905_r104","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2020.0036"},{"key":"S0033291726104905_r36","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2010.01.005"},{"key":"S0033291726104905_r71","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glab195"},{"key":"S0033291726104905_r28","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2024.2890"},{"key":"S0033291726104905_r107","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.25386"},{"key":"S0033291726104905_r15","doi-asserted-by":"publisher","DOI":"10.18632\/aging.100431"},{"key":"S0033291726104905_r103","doi-asserted-by":"publisher","DOI":"10.1177\/0004867419857814"},{"key":"S0033291726104905_r87","doi-asserted-by":"publisher","DOI":"10.1007\/s11695-017-2894-0"},{"key":"S0033291726104905_r38","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0447.2010.01582.x"},{"key":"S0033291726104905_r59","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2007.08.018"},{"key":"S0033291726104905_r67","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-023-02025-y"},{"key":"S0033291726104905_r70","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291724000345"},{"key":"S0033291726104905_r96","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-010-9476-y"},{"key":"S0033291726104905_r35","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2012.08.001"},{"key":"S0033291726104905_r3","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-024-02503-x"},{"key":"S0033291726104905_r30","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2020.103082"},{"key":"S0033291726104905_r57","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpsychires.2018.02.012"},{"key":"S0033291726104905_r61","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyg.2022.981379"},{"key":"S0033291726104905_r68","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.160.8.1396"},{"key":"S0033291726104905_r64","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcac233"},{"key":"S0033291726104905_r95","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2015.15070922"},{"key":"S0033291726104905_r46","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2017.73"},{"key":"S0033291726104905_r114","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-007-0906-9"},{"key":"S0033291726104905_r42","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/6613385"},{"key":"S0033291726104905_r47","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2015.227"},{"key":"S0033291726104905_r52","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2025.106005"},{"key":"S0033291726104905_r10","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2009.05.014"},{"key":"S0033291726104905_r33","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2026.01.020"},{"key":"S0033291726104905_r14","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2023.06.012"},{"key":"S0033291726104905_r77","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2017.02.104"},{"key":"S0033291726104905_r85","doi-asserted-by":"publisher","DOI":"10.1016\/j.rcpeng.2024.10.002"},{"key":"S0033291726104905_r105","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2023.15936"},{"key":"S0033291726104905_r24","doi-asserted-by":"publisher","DOI":"10.1111\/bdi.12200"},{"key":"S0033291726104905_r80","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2007.03.005"},{"key":"S0033291726104905_r101","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.23272"},{"key":"S0033291726104905_r106","doi-asserted-by":"publisher","DOI":"10.1037\/t49755-000"},{"key":"S0033291726104905_r66","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/949248"},{"key":"S0033291726104905_r92","doi-asserted-by":"publisher","DOI":"10.1111\/bdi.12485"},{"key":"S0033291726104905_r41","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2016.11.021"},{"key":"S0033291726104905_r44","doi-asserted-by":"publisher","DOI":"10.1093\/schbul\/sbx172"},{"key":"S0033291726104905_r58","doi-asserted-by":"publisher","DOI":"10.1093\/schbul\/sbaf101"},{"key":"S0033291726104905_r37","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0067346"},{"key":"S0033291726104905_r84","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.93246"},{"key":"S0033291726104905_r5","doi-asserted-by":"publisher","DOI":"10.1111\/bdi.12061"},{"key":"S0033291726104905_r56","first-page":"87","volume-title":"Comprehensive handbook of psychological assessment","volume":"2","author":"Kobak","year":"2004"},{"key":"S0033291726104905_r2","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.769309"},{"key":"S0033291726104905_r39","doi-asserted-by":"publisher","DOI":"10.37796\/2211-8039.1174"},{"key":"S0033291726104905_r11","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291718003008"},{"key":"S0033291726104905_r9","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpsychires.2014.10.002"},{"key":"S0033291726104905_r81","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpsychires.2016.08.019"},{"key":"S0033291726104905_r89","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.5908"},{"key":"S0033291726104905_r19","unstructured":"Centers for Disease Control and Prevention. (2025b). National diabetes statistics report. https:\/\/www.cdc.gov\/diabetes\/php\/data-research\/index.html"},{"key":"S0033291726104905_r31","doi-asserted-by":"publisher","DOI":"10.3390\/ijms12053117"},{"key":"S0033291726104905_r79","doi-asserted-by":"publisher","DOI":"10.1097\/HRP.0000000000000297"},{"key":"S0033291726104905_r86","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2014.12.030"},{"key":"S0033291726104905_r115","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2022.119415"},{"key":"S0033291726104905_r82","doi-asserted-by":"publisher","DOI":"10.1111\/acps.12603"},{"key":"S0033291726104905_r99","doi-asserted-by":"publisher","DOI":"10.1111\/j.2040-1124.2011.00170.x"},{"key":"S0033291726104905_r111","doi-asserted-by":"publisher","DOI":"10.1093\/biomet\/87.4.954"},{"key":"S0033291726104905_r76","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-021-01098-x"},{"key":"S0033291726104905_r26","doi-asserted-by":"publisher","DOI":"10.1007\/s11695-025-07964-9"}],"container-title":["Psychological Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cambridge.org\/core\/services\/aop-cambridge-core\/content\/view\/S0033291726104905","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T08:43:31Z","timestamp":1781772211000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cambridge.org\/core\/product\/identifier\/S0033291726104905\/type\/journal_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026]]},"references-count":107,"alternative-id":["S0033291726104905"],"URL":"https:\/\/doi.org\/10.1017\/s0033291726104905","relation":{},"ISSN":["0033-2917","1469-8978"],"issn-type":[{"value":"0033-2917","type":"print"},{"value":"1469-8978","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026]]},"assertion":[{"value":"\u00a9 The Author(s), 2026. 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":"e197"}}