FUNCTIONAL GENOMICS
STUDIES OF BIPOLAR DISORDER
Sabine
Bahn and Colleagues
Babraham
Institute, Cambridge, UK
Stanley
Laboratories, Johns Hopkins, Baltimore, MD, USA and Bethesda, MD, USA
Results
of microarray studies on human post-mortem tissue have suggested abnormalities
in lipid- and myelin-related genes in the prefrontal cortex of schizophrenia1-3.
Recently we found that key oligodendrocyte and myelination genes, including
transcription factors known to regulate these genes, were altered not only in
schizophrenia, but also in bipolar disorder. Although the notion that these
apparently diverse disorders may be related and may share common genetic and/or
epigenetic pathways has been considered for the last 100 years, the molecular
evidence supporting this assumption was still surprising. Thus, we now
undertook an extensive microarray investigation coupled with proteomics
(Fluorescent 2-D gels with biological variation analysis) and metabolomics
(high-resolution NMR) studies comparing the molecular signatures of a total of
150 post-mortem brains (50 schizophrenia, 50 bipolar and 50 control samples from
the Stanley brain collection; all prefrontal cortex) to further examine the
shared and disease-specific alterations at the gene, protein and metabolite
level. We will present results from the different functional genomics tiers
outlining both shared and distinct alterations in schizophrenia and bipolar
disorder.
1Hakah
Y. et al (2001) Genome-wide expression analysis reveals dysregulation of
myelination-related genes in chronic schizophrenia. Natl Acad Sci USA
98(8), 4746-4751.
2Pongrac
J. et al (2002) Gene expression profiling with DNA microarrays: advancing our
understanding of psychiatric disorders. Neurochem Res 27 (10), 1049-1063
3Mimmack
M.L. et al (2002) Gene expression analysis in schizophrenia: reproducible
up-regulation of several members of the apolipoprotein L family located in a
high-susceptibility locus for schizophrenia on chromosome 22. Proc Natl Acad
Sic USA 99 (7):4680-4685