The expression of proapoptosis genes is increased in bipolar disorder, but not in schizophrenia.

Post-mortem studies conducted over the past 15 years suggest that apoptosis could play a role in the pathophysiology of bipolar disorder (BD) and, to a lesser degree, schizophrenia (SZ). To test this hypothesis, we have performed a post hoc analysis of an extant gene expression profiling database obtained from the hippocampus using a novel methodology with improved sensitivity. Consistent with the working hypothesis, BDs showed a marked upregulation of 19 out of 44 apoptosis genes; however, contrary to the hypothesis, the SZ group showed a downregulation of genes associated with apoptotic injury and death. These changes in the regulation of apoptosis genes were validated using quantitative RT-PCR. Additionally, antioxidant genes showed a marked downregulation in BDs, suggesting that accumulation of free radicals might occur in the setting of a previously reported decrease of the electron transport chain in this disorder. Overall, the changes seen in BDs and SZs do not appear to be related to exposure to either neuroleptics or mood stabilizers. We conclude that fundamental differences in the genetic regulation of apoptosis and antioxidant genes may help discriminate between the pathophysiology of BD and SZ and potentially point to new treatment strategies that are specific for each disorder.