OLIGODENDROCYTE DYSFUNCTION IN
SCHIZOPHRENIA AND BIPOLAR DISORDER
Dmitri Takchev, Michael L. Mimmack,
Margaret M. Ryan, Matt Wayland, Tom Freeman, Peter B. Jones, Michael Starkey,
Maree J. Webster, Robert H. Yolken, Sabine Bahn
Lancet 362:798-805, 2003
of array studies have suggested abnormalities in expression of lipid and
myelin-related genes in schizophrenia. Here, we investigated
oligodendrocyte-specific and myelination-associated gene expression in
schizophrenia and bipolar affective disorder.
We used samples from the Stanley brain collection, consisting of 15
schizophrenia, 15 bipolar affective disorder, and 15 control brains.
Indexing-based differential display PCR was done to screen for differences in
gene expression in schizophrenia patients versus controls. Results were
cross-validated with quantitative PCR, which was also used to investigate
expression profiles of 16 other oligodendrocyte and myelin genes in
schizophrenia and bipolar disorder. These genes were further investigated with
an ongoing microarray analysis.
Results of differential display and quantitative PCR analysis showed a reduction
of key oligodendrocyte-related and myelin-related genes in schizophrenia and
bipolar patients; expression changes for both disorders showed a high degree of
overlap. Microarray results of the same genes investigated by quantitative
PCR correlated well overall.
Schizophrenia and bipolar brains showed downregulation of key oligodendrocyte
and myelination genes, including transcription factors that regulate these
genes, compared with control brains. These results lend support to and
extend observations from other microarray investigations. Our study also
showed similar expression changes to the schizophrenia group in bipolar brains,
which thus lends support to the notion that the disorders share common causative
and pathophysiological pathways.