Central autonomic control of the heart, angina, and pathogenic mechanisms of post-myocardial infarction depression.

Depression can develop in 20% of the patients with a myocardial infarction (MI). Pathobiological mechanisms underlying the development of mood disorders in these patients are unknown. Since post-MI depression has been associated with increased risk of mortality we hypothesized that dysfunction of limbic circuitry is part of the pathogenic processes. Both mood and cardiovascular functions are controlled by the limbic system. Here, we will review a set of experiments that support this hypothesis. Using the retrograde transneuronal transport of pseudorabies virus central autonomic cardiomotor circuitry was identified and Fos protein expression was used for characterization of networks participating in cardiac pain perception, evaluation, and initiation of coping responses. A modified conscious rat model of acute heart pain was employed for induction of cerebral Fos protein expression. Experiments investigating the effects of MI on cerebral activity in the rat showed a selective regional endothelial leakage mainly in the prefrontal cortex, and most severely in the anterior cingulate cortex. This effect was mimicked with intravenous injections of recombinant Tumor Necrosis Factor alpha, which led to the hypothesis that post-MI depression evolves from selective dysfunction of the prefrontal, anterior cingulate cortex in response to (excessive) release of mediators of inflammation. Evidence is provided that cingulate cortex dysfunction may underlie occurrence of mood disorders and derangement of cardiac autonomic control, which would explain the increased risk of mortality associated with post-MI depression.