Increased cortical expression of an RNA editing enzyme occurs in major depressive suicide victims.

Abstract

RNA editing is a posttranscriptional process which critically modulates the function of several neurotransmitter receptors regulating mood, anxiety, learning, and memory. Data from several postmortem studies have shown increased 5-hydroxytryptamine-2C receptor RNA editing in mood disorders and suicide, and therefore the 5-hydroxytryptamine-2C receptor might be expected to have reduced signal transduction in these patients. In this study, we have tested the hypothesis that the expression levels of the enzymes which catalyze RNA editing, adenosine deaminase acting on RNA 1 (ADAR1) and ADAR2, are also abnormal in suicide. Gene expression was measured in the dorsolateral prefrontal cortex of individuals from the Stanley Consortium Brain series, which includes patients with schizophrenia (n=15), major depression (n=15), bipolar disorder (n=15), and a comparison group (n=14). Of the psychiatric patients, 20 were suicide victims. ADAR1 expression was found to be significantly increased in major depressive suicide victims compared with patients who did not commit suicide. Neither ADAR1 nor ADAR2 expression was altered in any of the other diagnostic groups. These data indicate that ADAR1 could play a role in the pathophysiology of suicide in patients with major depression.