There are to date no objective clinical laboratory blood tests for mood disorders. The current reliance on patient self-report of symptom severity and on the clinicians’ impression is a rate limiting step in effective treatment and new drug development.

Investigators from Indiana propose, and provide proof of principle for, an approach to help identify blood biomarkers for mood state. They measured whole-genome gene expression differences in blood samples from subjects with bipolar disorder that had low mood vs. those that had high mood at the time of the blood draw, and separately, changes in gene expression in brain and blood of a mouse pharmacogenomic model.

They then integrated their human blood gene expression data with animal model gene expression data, human genetic linkage/association data, and human postmortem brain data, an approach called Convergent Functional Genomics, as a Bayesian strategy for cross-validating and prioritizing findings.

Topping the list of candidate blood biomarker genes they are five genes involved in myelination (Mbp, Edg2, Mag, Pmp22 and Ugt8), and six genes involved in growth factor signaling (Fgfr1, Fzd3, Erbb3, Igfbp4, Igfbp6, and Ptprm).

All of these genes have prior evidence of differential expression in human postmortem brains from mood disorder subjects. A predictive score developed based on a panel of ten top candidate biomarkers (five for high mood, five for low mood) shows sensitivity and specificity for high mood and low mood states, in two independent cohorts. These studies suggest that blood biomarkers may offer an unexpectedly informative window into brain functioning and disease state.

Moreover, this work uncovers an intriguing overlap between genes involved in cancer biology and genes involved in mood regulation.

###

Citation source: Molecular Psychiatry advance online publication 26 FEBRUARY 2008

For further information on this article, please contact the Corresponding Author:

Alexander B. Niculescu III, MD, PhD
Assistant Professor of Psychiatry, Medical Neurobiology and Neuroscience
Indiana University School of Medicine
Staff Psychiatrist, Indianapolis VA Medical Center
Director, INBRAIN and Laboratory of Neurophenomics
Institute of Psychiatric Research
791 Union Drive
Indianapolis, IN 46202-4887
tel. 317-274-6544
fax. 317-274-1365
e-mail: .(JavaScript must be enabled to view this email address)

OR

Mary Hardin
Media Manager
Indiana University School of Medicine
317-274-5456 (desk)
317-695-4090 (cell)
317-274-7722 (main office)

Molecular Psychiatry is a peer-reviewed independent journal that publishes groundbreaking research in psychiatry and related fields. The journal’s Impact Factor is 11.804, 2nd of 95 in Psychiatry
Journal e-Mail: .(JavaScript must be enabled to view this email address)

Editor: Julio Licinio, M.D.
University of Miami Miller School of Medicine

Identifying Blood Biomarkers For Mood Disorders Using Convergent Functional Genomics

H. Le-Niculescu 1, 2, 3 ,
S. M. Kurian 4 ,
N. Yehyawi 1,5,
C. Dike 1,5,
S.D. Patel 1,3,
H.J. Edenberg 6,
M. T. Tsuang 7,
D. R. Salomon 4,
J. I. Nurnberger Jr 3 , and
A. B. Niculescu 1, 2, 3, 5 ¶

1 Laboratory of Neurophenomics,
2 INBRAIN,
3 Institute of Psychiatric Research, Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN 46202;
4 Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037;
5 Indianapolis VA Medical Center, Indianapolis, IN 46202;
6 Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN;
7 Department of Psychiatry, UC San Diego, La Jolla, CA 92037.

Contact: Alexander B. Niculescu III
.(JavaScript must be enabled to view this email address)
317-274-6544
Molecular Psychiatry