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Sympathetic activity in major depressive disorder: identifying those at increased cardiac risk?

Barton, David Aa,c; Dawood, Tyea,d; Lambert, Elisabeth Aa; Esler, Murray Da; Haikerwal, Deepaka; Brenchley, Celiaa; Socratous, Florentiaa; Kaye, David Mb; Schlaich, Markus Pa; Hickie, Iane; Lambert, Gavin Wa

doi: 10.1097/HJH.0b013e32829baae7
Original papers: Sympathetic activity

Background Evidence exists linking major depressive disorder (MDD) with clinical cardiovascular events. The importance of the sympathetic nervous system in the generation of cardiac risk in other contexts is established.

Objective To examine the importance of the sympathetic nervous system in the generation of cardiac risk in patients with major depressive disorder (MDD).

Methods Studies were performed in 39 patients meeting the Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) criteria for MDD and in 76 healthy subjects. Treatment for patients consisted of selective serotonin reuptake inhibition (SSRI) 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, particularly in the heart and for the whole body, in patients with MDD followed a bimodal distribution. Elevated values were observed in patients with co-morbid panic disorder (P = 0.006). Consistent with a defect in noradrenaline reuptake, the cardiac extraction of tritiated noradrenaline (0.80 ± 0.01 versus 0.56 ± 0.04%, P < 0.001) and cardiac dihydroxyphenylglycol overflow (109 ± 8 versus 73 ± 11, P = 0.01) were reduced in patients with MDD. SSRI therapy abolished the excessive sympathetic activation, with whole body 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, including in the sympathetic outflow to the heart. Treatment with an SSRI may reduce sympathetic activity in a manner likely to reduce cardiac risk.

aHuman Neurotransmitter Laboratory, Australia

bWynn Department of Metabolic Cardiology Baker Heart Research Institute, Melbourne, Australia

cDepartment of Psychological Medicine, Australia

dAlfred Hospital CECS, Monash University, Melbourne, Australia

eBrain and Mind Research Institute, Sydney University, Sydney, Australia

Received 8 February, 2007

Revised 22 May, 2007

Accepted 28 May, 2007

Correspondence to Dr Gavin Lambert, Baker Heart Research Institute, PO Box 6492 St Kilda Road Central, Melbourne, Victoria 8008, Australia Tel: +61 3 85321346; fax: +61 3 85321100; e-mail:

© 2007 Lippincott Williams & Wilkins, Inc.