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Dentate gyrus−cornu ammonis (CA) 4 volume is decreased and associated with depressive episodes and lipid peroxidation in bipolar II disorder: Longitudinal and cross‐sectional analyses
Author(s) -
Elvsåshagen Torbjørn,
Zuzarte Pedro,
Westlye Lars T,
Bøen Erlend,
Josefsen Dag,
Boye Birgitte,
Hol Per K,
Malt Ulrik F,
Young L Trevor,
Andreazza Ana C
Publication year - 2016
Publication title -
bipolar disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.285
H-Index - 129
eISSN - 1399-5618
pISSN - 1398-5647
DOI - 10.1111/bdi.12457
Subject(s) - dentate gyrus , hippocampal formation , bipolar disorder , medicine , bipolar ii disorder , hippocampus , oxidative stress , endocrinology , psychology , chemistry , neuroscience , pathology , lithium (medication)
Objectives Reduced dentate gyrus volume and increased oxidative stress have emerged as potential pathophysiological mechanisms in bipolar disorder. However, the relationship between dentate gyrus volume and peripheral oxidative stress markers remains unknown. Here, we examined dentate gyrus–cornu ammonis ( CA ) 4 volume longitudinally in patients with bipolar II disorder ( BD ‐ II ) and healthy controls and investigated whether BD ‐ II is associated with elevated peripheral levels of oxidative stress. Methods We acquired high‐resolution structural 3T‐magnetic resonance imaging ( MRI ) images and quantified hippocampal subfield volumes using an automated segmentation algorithm in individuals with BD ‐ II (n=29) and controls (n=33). The participants were scanned twice, at study inclusion and on average 2.4 years later. In addition, we measured peripheral levels of two lipid peroxidation markers (4‐hydroxy‐2‐nonenal [4‐ HNE ] and lipid hydroperoxides [LPH]). Results First, we demonstrated that the automated hippocampal subfield segmentation technique employed in this work reliably measured dentate gyrus– CA 4 volume. Second, we found a decreased left dentate gyrus– CA 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‐ HNE was elevated in BD ‐ II and that 4‐ HNE was negatively associated with left and right dentate gyrus– CA 4 volumes in patients. Conclusions 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.