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A single blinded equivalence randomized controlled maintenance trial was conducted in a prospective cohort of first-episode mania (FEM) patients (<jats:italic>n<\/jats:italic>=26) to longitudinally compare the putative protective effects of lithium and quetapine on grey and white matter volume. A healthy control sample was also collected (<jats:italic>n<\/jats:italic>=20). Using structural MRI scans, voxel-wise grey and white matter volumes at baseline and changes over time in response to treatment were investigated. Patients were assessed at three time points (baseline, 3 and 12-month follow-up), whereas healthy controls were assessed at two time points (baseline and 12-month follow-up). Patients were randomized to lithium (serum level 0.6\u2009mmol\u2009l<jats:sup>\u22121<\/jats:sup>, <jats:italic>n<\/jats:italic>=20) or quetiapine (flexibly dosed up to 800\u2009mg per day, <jats:italic>n<\/jats:italic>=19) monotherapy. At baseline, compared with healthy control subjects, patients with FEM showed reduced grey matter in the orbitofrontal cortex, anterior cingulate, inferior frontal gyrus and cerebellum. In addition, patients had reduced internal capsule white matter volume bilaterally (<jats:italic>t<\/jats:italic><jats:sub>1,66<\/jats:sub>&gt;3.20, <jats:italic>P<\/jats:italic>&lt;0.01). Longitudinally, there was a significant treatment \u00d7 time effect only in the white matter of the left internal capsule (F<jats:sub>2,112<\/jats:sub>=8.54, <jats:italic>P<\/jats:italic>&lt;0.01). <jats:italic>Post hoc<\/jats:italic> testing showed that, compared with baseline, lithium was more effective than quetiapine in slowing the progression of white matter volume reduction after 12 months (<jats:italic>t<\/jats:italic><jats:sub>1,24<\/jats:sub>=3.76, <jats:italic>P<\/jats:italic>&lt;0.01). Our data support the role of lithium but not quetiapine therapy in limiting white matter reduction early in the illness course after FEM.<\/jats:p>","DOI":"10.1038\/tp.2016.281","type":"journal-article","created":{"date-parts":[[2017,1,24]],"date-time":"2017-01-24T16:51:51Z","timestamp":1485276711000},"page":"e1011-e1011","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":58,"title":["Neuroprotection after a first episode of mania: a randomized controlled maintenance trial comparing the effects of lithium and quetiapine on grey and white matter volume"],"prefix":"10.1038","volume":"7","author":[{"given":"M","family":"Berk","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O","family":"Dandash","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Daglas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S M","family":"Cotton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Allott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Fornito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Suo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Klauser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B","family":"Liberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Henry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Macneil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Hasty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"McGorry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cs","family":"Pantelis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Y\u00fccel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,1,24]]},"reference":[{"key":"BFtp2016281_CR1","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1192\/bjp.172.1.23","volume":"172","author":"LV Kessing","year":"1998","unstructured":"Kessing LV, Andersen PK, Mortensen PB, Bolwig TG . 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PM has received investigator-initiated research grants from Astra Zeneca, Janssen Cilag, Eli Lilly and BMS. He has received honoraria for educational events from Janssen Cilag, Eli Lilly, BMS, Astra Zeneca, Pfizer and Lundbeck. CP has participated on Advisory Boards for Janssen Cilag, Astra Zeneca, Lundbeck and Servier, and has received honoraria for talks presented at educational meetings organised by Astra Zeneca, Janssen Cilag, Eli Lilly, Pfizer, Lundbeck and Shire. CM has received honoraria for talks at meetings organised by Astra Zeneca, Janssen Cilag, Sanofi Synthelabo and Eli Lilly, and has been on a consultation panel for Eli Lilly. BL received funding from Svenska L\u00e4kares\u00e4llskapet (The Swedish Society of Medicine, SLS-403101), and Forskningsr\u00e5det, Karolinska Institutet, Stockholm County Council, Sweden. The remaining authors declare no conflicts of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}