{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T06:56:46Z","timestamp":1771484206485,"version":"3.50.1"},"reference-count":48,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,12,1]],"date-time":"2018-12-01T00:00:00Z","timestamp":1543622400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100008207","name":"AstraZeneca Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008207","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Bipolar Disorders"],"published-print":{"date-parts":[[2019,2]]},"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>A sizable fraction of people with bipolar I disorder (<jats:styled-content style=\"fixed-case\">BDI<\/jats:styled-content>) experience a deteriorating clinical course with increasingly frequent mood episodes and chronic disability. This is believed to result from neurobiological illness progression, or neuroprogression. Excessive weight gain predicts neuroprogression across multiple brain illnesses, but no prospective studies have investigated this in<jats:styled-content style=\"fixed-case\">BDI<\/jats:styled-content>. The objective of this study was to determine whether<jats:styled-content style=\"fixed-case\">BDI<\/jats:styled-content>patients who experienced clinically significant weight gain (<jats:styled-content style=\"fixed-case\">CSWG<\/jats:styled-content>; gaining \u22657% of baseline weight) over 12\u00a0months had greater 12\u2010month brain volume loss in frontal and temporal regions important to<jats:styled-content style=\"fixed-case\">BDI<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In 55 early\u2010stage<jats:styled-content style=\"fixed-case\">BDI<\/jats:styled-content>patients we measured (i) rates of<jats:styled-content style=\"fixed-case\">CSWG<\/jats:styled-content>, (ii) the number of days with mood symptoms, using<jats:styled-content style=\"fixed-case\">NIMH<\/jats:styled-content>LifeCharts, and (iii) baseline and 12\u2010month brain volumes, using 3T<jats:styled-content style=\"fixed-case\">MRI<\/jats:styled-content>. We quantified brain volumes using the longitudinal processing stream in FreeSurfer v6.0. We used general linear models for repeated measures to investigate whether<jats:styled-content style=\"fixed-case\">CSWG<\/jats:styled-content>predicted volume loss, adjusting for potentially confounding clinical and treatment variables.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>After correction for multiple comparisons,<jats:styled-content style=\"fixed-case\">CSWG<\/jats:styled-content>in patients predicted greater volume loss in the left orbitofrontal cortex (effect size [<jats:styled-content style=\"fixed-case\">ES<\/jats:styled-content>; Cohen's<jats:italic>d<\/jats:italic>]\u00a0=\u00a0\u22121.01,<jats:italic>P<\/jats:italic>\u00a0=\u00a00.002), left cingulate gyrus (<jats:styled-content style=\"fixed-case\">ES<\/jats:styled-content>\u00a0=\u00a0\u22121.31,<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001), and left middle temporal gyrus (<jats:styled-content style=\"fixed-case\">ES<\/jats:styled-content>\u00a0=\u00a0\u22120.96,<jats:italic>P<\/jats:italic>\u00a0=\u00a00.004). Middle temporal volume loss predicted more days with depression (\u03b2\u00a0=\u00a0\u22120.406,<jats:italic>P<\/jats:italic>\u00a0=\u00a00.010).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These are the first prospective data on weight gain and neuroprogression in<jats:styled-content style=\"fixed-case\">BDI<\/jats:styled-content>.<jats:styled-content style=\"fixed-case\">CSWG<\/jats:styled-content>predicted neuroprogression, and neuroprogression predicted a worse clinical illness course. Trials of weight loss interventions are needed to confirm the causal direction of the weight gain\u2010neuroprogression relationship, and to determine whether weight loss is a disease\u2010modifying treatment.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bdi.12722","type":"journal-article","created":{"date-parts":[[2018,11,13]],"date-time":"2018-11-13T15:35:41Z","timestamp":1542123341000},"page":"50-60","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Weight gain as a predictor of frontal and temporal lobe volume loss in bipolar disorder: A prospective<scp>MRI<\/scp>study"],"prefix":"10.1111","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8713-7311","authenticated-orcid":false,"given":"David J","family":"Bond","sequence":"first","affiliation":[{"name":"Department of Psychiatry University of Minnesota Medical School Minneapolis Minnesota"},{"name":"Mood Disorders Centre University of British Columbia 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