The disease mechanism of bipolar disorder remains unknown. Recent studies
have provided evidence for abnormal gene expression in bipolar disorder.
To determine the expression of 12 558 nuclear genes in the human
hippocampus in healthy control subjects and those with bipolar disorder or
We used gene arrays to study messenger RNA expression. Data were verified
with a real-time quantitative polymerase chain reaction assay.
We studied 10 healthy control subjects, 9 subjects with bipolar disorder,
and 8 subjects with schizophrenia.
The expression of nuclear messenger RNA coding for mitochondrial proteins
was significantly decreased in the hippocampus in subjects with bipolar disorder
but not in those with schizophrenia. Subjects with bipolar disorder were characterized
by a pronounced and extensive decrease in the expression of genes regulating
oxidative phosphorylation and the adenosine triphosphate–dependent process
of proteasome degradation.
These findings point toward a widespread dysregulation of mitochondrial
energy metabolism and downstream deficits of adenosine triphosphate–dependent
processes in bipolar disorder.