The authors of this paper do not have any commercial associations that might pose a conflict of interest in connection with this manuscript.
Increased peripheral blood expression of electron transport chain genes in bipolar depression
Article first published online: 22 DEC 2010
© 2010 John Wiley and Sons A/S
Volume 12, Issue 8, pages 813–824, December 2010
How to Cite
Beech, R. D., Lowthert, L., Leffert, J. J., Mason, P. N., Taylor, M. M., Umlauf, S., Lin, A., Lee, J. Y., Maloney, K., Muralidharan, A., Lorberg, B., Zhao, H., Newton, S. S., Mane, S., Epperson, C. N., Sinha, R., Blumberg, H. and Bhagwagar, Z. (2010), Increased peripheral blood expression of electron transport chain genes in bipolar depression. Bipolar Disorders, 12: 813–824. doi: 10.1111/j.1399-5618.2010.00882.x
- Issue published online: 22 DEC 2010
- Article first published online: 22 DEC 2010
- Received 7 April 2010, revised and accepted for publication 7 October 2010
- bipolar disorder;
- gene expression;
- oxidative phosphorylation;
Beech RD, Lowthert L, Leffert JJ, Mason PN, Taylor MM, Umlauf S, Lin A, Lee JY, Maloney K, Muralidharan A, Lorberg B, Zhao H, Newton SS, Mane S, Epperson CN, Sinha R, Blumberg H, Bhagwagar Z. Increased peripheral blood expression of electron transport chain genes in bipolar depression. Bipolar Disord 2010: 12: 813–824. © 2010 The Authors.Journal compilation © 2010 John Wiley & Sons A/S.
Objective: To identify specific genetic pathways showing altered expression in peripheral blood of depressed subjects with bipolar disorder (BPD).
Methods: Illumina Sentrix BeadChip (Human-6v2) microarrays containing >48,000 transcript probes were used to measure levels of gene expression in peripheral blood from 20 depressed subjects with BPD and in 15 healthy control subjects. Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) was used to confirm a subset of these differences.
Results: A total of 1,180 genes were differentially expressed between subjects with BPD and healthy controls (fold-change >1.3, false discovery rate-corrected p < 0.05, covaried for age and sex). Of these, 559 genes were up-regulated in BPD subjects and 621 were down-regulated. Surprisingly, there was no difference between medicated (n = 11) and unmedicated (n = 9) subjects with BPD for any of these genes. Pathway analysis using GeneGo MetaCore software showed that the most significantly affected pathway was the mitochondrial electron transport chain (ETC). Of the 85 objects (genes or proteins) in this pathway, 22 were up-regulated and 2 down-regulated in subjects with BPD. qRT-PCR confirmed up-regulation of nuclear encoded ETC genes in complexes I, III, IV, and V and, in addition, demonstrated up-regulation of mitochondrially encoded genes in each of these complexes.
Conclusion: These results suggest that increased expression of multiple components of the mitochondrial ETC may be a primary deficit in bipolar depression, rather than an effect of medication.