H. Le-Niculescu, M.J. McFarland, and C.A. Ogden contributed equally to this work.
Article first published online: 4 FEB 2008
Copyright © 2008 Wiley-Liss, Inc.
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
Volume 147B, Issue 2, pages 134–166, 5 March 2008
How to Cite
Le-Niculescu, H., McFarland, M.J., Ogden, C.A., Balaraman, Y., Patel, S., Tan, J., Rodd, Z.A., Paulus, M., Geyer, M.A., Edenberg, H.J., Glatt, S.J., Faraone, S.V., Nurnberger, J.I., Kuczenski, R., Tsuang, M.T. and Niculescu, A.B. (2008), Phenomic, Convergent Functional Genomic, and biomarker studies in a stress-reactive genetic animal model of bipolar disorder and co-morbid alcoholism. Am. J. Med. Genet., 147B: 134–166. doi: 10.1002/ajmg.b.30707
Please cite this article as follows: Le-Niculescu H, McFarland MJ, Ogden CA, Balaraman Y, Patel S, Tan J, Rodd ZA, Paulus M, Geyer MA, Edenberg HJ, Glatt SJ, Faraone SV, Nurnberger JI, Kuczenski R, Tsuang MT, Niculescu AB. 2008. Phenomic, Convergent Functional Genomic, and Biomarker Studies in a Stress-Reactive Genetic Animal Model of Bipolar Disorder and Co-Morbid Alcoholism. Am J Med Genet Part B 147B:134–166.
MAG has an equity interest in San Diego Instruments, Inc.
- Issue published online: 21 FEB 2008
- Article first published online: 4 FEB 2008
- Manuscript Accepted: 3 DEC 2007
- Manuscript Received: 31 OCT 2007
- Indiana Genomics Initiative of Indiana University (INGEN)
- Indiana Center for Biomarker Research In Neuropsychiatry (INBRAIN)
- NIMH. Grant Number: R01 MH071912-01
- clock gene;
- bipolar disorder;
We had previously identified the clock gene D-box binding protein (Dbp) as a potential candidate gene for bipolar disorder and for alcoholism, using a Convergent Functional Genomics (CFG) approach. Here we report that mice with a homozygous deletion of DBP have lower locomotor activity, blunted responses to stimulants, and gain less weight over time. In response to a chronic stress paradigm, these mice exhibit a diametric switch in these phenotypes. DBP knockout mice are also activated by sleep deprivation, similar to bipolar patients, and that activation is prevented by treatment with the mood stabilizer drug valproate. Moreover, these mice show increased alcohol intake following exposure to stress. Microarray studies of brain and blood reveal a pattern of gene expression changes that may explain the observed phenotypes. CFG analysis of the gene expression changes identified a series of novel candidate genes and blood biomarkers for bipolar disorder, alcoholism, and stress reactivity. © 2008 Wiley-Liss, Inc.