Elevated serum measures of lipid peroxidation and abnormal prefrontal white matter in euthymic bipolar adults: toward peripheral biomarkers of bipolar disorder.
Diffusion tensor imaging (DTI) studies consistently reported abnormalities in fractional anisotropy (FA) and radial diffusivity (RD), measures of the integrity of white matter (WM), in bipolar disorder (BD), that may reflect underlying pathophysiologic processes. There is, however, a pressing need to identify peripheral measures that are related to these WM measures, to help identify easily obtainable peripheral biomarkers of BD. Given the high lipid content of axonal membranes and myelin sheaths, and that elevated serum levels of lipid peroxidation are reported in BD, these serum measures may be promising peripheral biomarkers of underlying WM abnormalities in BD. We used DTI and probabilistic tractography to compare FA and RD in ten prefrontal-centered WM tracts, 8 of which are consistently shown to have abnormal FA (and/or RD) in BD, and also examined serum lipid peroxidation (lipid hydroperoxides, LPH and 4-hydroxy-2-nonenal, 4-HNE), in 24 currently euthymic BD adults (BDE) and 19 age- and gender-matched healthy adults (CONT). There was a significant effect of group upon FA in these a priori WM tracts (BDE<CONT: F[1,41]=6.8; P=0.013) and RD (BDE>CONT: F[1,41]=10.3; P=0.003), and a significant between-group difference in LPH (BDE>CONT: t[40]=2.4; P=0.022), but not in 4-HNE. Multivariate multiple regression analyses revealed that LPH variance explained, respectively, 59 and 51% of the variance of FA and RD across all study participants. This is the first study to examine relationships between measures of WM integrity and peripheral measures of lipid peroxidation. Our findings suggest that serum LPH may be useful in the development of a clinically relevant, yet easily obtainable and inexpensive, peripheral biomarkers of BD.
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
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Versace
1] Departments of Psychiatry and Pharmacology, University of Toronto, Toronto, Ontario, Canada [2] Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
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Andreazza
1] Departments of Psychiatry and Pharmacology, University of Toronto, Toronto, Ontario, Canada [2] Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
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Young
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
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Fournier
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
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Almeida
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
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Stiffler
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
J C
JC
Lockovich
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
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Aslam
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
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Pollock
1] Departments of Psychiatry and Pharmacology, University of Toronto, Toronto, Ontario, Canada [2] Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
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Park
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
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Nimgaonkar
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
D J
DJ
Kupfer
1] Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA [2] Department of Psychological Medicine, Cardiff University School of Medicine, Cardiff, UK.
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Phillips
D000328:Adult; D000447:Aldehydes / Q000097:blood; D016880:Anisotropy; D015415:Biomarkers / Q000097:blood; D001714:Bipolar Disorder / Q000097:blood* / Q000188:drug therapy / Q000473:pathology*; D001921:Brain / Q000473:pathology*; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D015227:Lipid Peroxidation; D008054:Lipid Peroxides / Q000097:blood; D008297:Male; D015233:Models, Statistical; D015999:Multivariate Analysis; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D009434:Neural Pathways / Q000473:pathology*; D017397:Prefrontal Cortex / Q000473:pathology; D012815:Signal Processing, Computer-Assisted
D000447:Aldehydes; D015415:Biomarkers; D008054:Lipid Peroxides; C027576:4-hydroxy-2-nonenal