Phosphodiesterase-4A expression is reduced in cerebella of patients with bipolar disorder

Objective The cAMP-specific phosphodiesterase-4 (PDE4) gene family has four members (PDE4 A, B, C, and D) and is the target of several potential therapeutic inhibitors. Recently, PDE4A5 has been shown to bind with disrupted in schizophrenia 1 (DISC1) which has been identified as a risk factor for schizophrenia, bipolar disorder, and major depression. We sought to examine whether PDE4A5 expression was altered in cerebella of patients with schizophrenia, bipolar disorder, and major depression. Methods We measured protein levels of PDE4A isoforms in cerebella of patients with schizophrenia, bipolar disorder, and major depression versus matched controls using sodium dodecyl sulfate polyacrylamide gel electrophoresis and western blotting. Results We observed that specific isoforms of PDE4A were reduced in cerebella of patients with bipolar disorder, whereas there was no change in patients with schizophrenia or major depression. Conclusion Our results are the first to show that PDE4A expression is altered in patients with bipolar disorder and provide potential new therapeutic avenues for treatment of this disorder.