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However, the relationship between dentate gyrus volume and peripheral oxidative stress markers remains unknown. Here, we examined dentate gyrus\u2013cornu ammonis (<jats:styled-content style=\"fixed-case\">CA<\/jats:styled-content>) 4 volume longitudinally in patients with bipolar <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content> disorder (<jats:styled-content style=\"fixed-case\">BD<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">II<\/jats:styled-content>) and healthy controls and investigated whether <jats:styled-content style=\"fixed-case\">BD<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">II<\/jats:styled-content> is associated with elevated peripheral levels of oxidative stress.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We acquired high\u2010resolution structural 3T\u2010magnetic resonance imaging (<jats:styled-content style=\"fixed-case\">MRI<\/jats:styled-content>) images and quantified hippocampal subfield volumes using an automated segmentation algorithm in individuals with <jats:styled-content style=\"fixed-case\">BD<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">II<\/jats:styled-content> (n=29) and controls (n=33). The participants were scanned twice, at study inclusion and on average 2.4\u00a0years later. In addition, we measured peripheral levels of two lipid peroxidation markers (4\u2010hydroxy\u20102\u2010nonenal [4\u2010<jats:styled-content style=\"fixed-case\">HNE<\/jats:styled-content>] and lipid hydroperoxides [LPH]).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>First, we demonstrated that the automated hippocampal subfield segmentation technique employed in this work reliably measured dentate gyrus\u2013<jats:styled-content style=\"fixed-case\">CA<\/jats:styled-content>4 volume. Second, we found a decreased left dentate gyrus\u2013<jats:styled-content style=\"fixed-case\">CA<\/jats:styled-content>4 volume in patients and that a larger number of depressive episodes between T1 and T2 predicted greater volume decline. Finally, we showed that 4\u2010<jats:styled-content style=\"fixed-case\">HNE<\/jats:styled-content> was elevated in <jats:styled-content style=\"fixed-case\">BD<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">II<\/jats:styled-content> and that 4\u2010<jats:styled-content style=\"fixed-case\">HNE<\/jats:styled-content> was negatively associated with left and right dentate gyrus\u2013<jats:styled-content style=\"fixed-case\">CA<\/jats:styled-content>4 volumes in patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These results are consistent with a role for the dentate gyrus in the pathophysiology of bipolar disorder and suggest that depressive episodes and elevated oxidative stress might contribute to hippocampal volume decreases. In addition, these findings provide further support for the hypothesis that peripheral lipid peroxidation markers may reflect brain alterations in bipolar disorders.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bdi.12457","type":"journal-article","created":{"date-parts":[[2016,12,20]],"date-time":"2016-12-20T09:52:57Z","timestamp":1482227577000},"page":"657-668","source":"Crossref","is-referenced-by-count":21,"title":["Dentate gyrus\u2212cornu ammonis (CA) 4 volume is decreased and associated with depressive episodes and lipid peroxidation in bipolar <scp>II<\/scp> disorder: Longitudinal and cross\u2010sectional analyses"],"prefix":"10.1111","volume":"18","author":[{"given":"Torbj\u00f8rn","family":"Elvs\u00e5shagen","sequence":"first","affiliation":[{"name":"Department of Neurology Oslo University Hospital  Oslo Norway"},{"name":"Norwegian Centre for Mental Disorders Research Oslo University Hospital  Oslo Norway"},{"name":"Institute of Clinical Medicine University of Oslo  Oslo 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