Background: There exists a growing body of evidence linking psychological abnormalities, particularly major depressive disorder (MDD), with clinical cardiovascular events. While the mechanism of increased risk attributable to MDD is not known the importance of the sympathetic nervous system in the generation of cardiac risk in other contexts is well established.
Aims: To determine the clinical characteristics underpinning the pattern of sympathetic activity in patients with MDD.
Methods: Studies were performed in 39 patients meeting the DSM-IV criteria for MDD and in 76 healthy subjects. Treatment for patients consisted of selective serotonin reuptake inhibition for 12 weeks. Whole body and cardiac sympathetic activity were examined using noradrenaline isotope dilution methodology and sympathetic nerve recording techniques. Measurement of the extraction of infused tritiated noradrenaline by the heart, and estimation of cardiac dihydroxyphenylglycol production provided direct quantification of neuronal noradrenaline reuptake.
Results: Sympathetic activity in patients with MDD followed a bimodal distribution. Consistent with a defect in noradrenaline reuptake, the cardiac extraction of tritiated noradrenaline (0.80 ± 0.01 v 0.56 ± 0.04%, P < 0.001) and cardiac dihydroxyphenylglycol overflow (109 ± 8 v 73 ± 11, P = 0.01) were reduced in patients with MDD. SSRI therapy abolished the excessive sympathetic activation, with noradrenaline spillover falling from 518 ± 83 to 290 ± 41 ng/min, P = 0.008.
Conclusions: We have identified a subset of patients with MDD in whom sympathetic nervous activity is extraordinarily high. Treatment with an SSRI modifies sympathetic nervous activity in a manner likely to reduce cardiac risk.
