Molecular evidence for mitochondrial dysfunction in bipolar disorder

Background: The disease mechanism of bipolar disorder remains unknown. Recent studies have provided evidence for abnormal gene expression in bipolar disorder. Objective: To determine the expression of 12 558 nuclear genes in the human hippocampus in healthy control subjects and those with bipolar disorder or schizophrenia. Design: We used gene arrays to study messenger RNA expression. Data were verified with a real-time quantitative polymerase chain reaction assay. Subjects: We studied 10 healthy control subjects, 9 subjects with bipolar disorder, and 8 subjects with schizophrenia. Results: 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. Conclusions: These findings point toward a widespread dysregulation of mitochondrial energy metabolism and downstream deficits of adenosine triphosphate-dependent processes in bipolar disorder.