Vidi et al reported a 21% prevalence of anxiety or depression in their 34 patients with tako-tsubo cardiomyopathy (TTC), making these mood disorders even more common in this group of patients than more traditional cardiac risk factors such as diabetes and smoking. This observation is consistent with those of Mudd et al, who reported a 40% prevalence of anxiety or depression in 110 patients with TTC. The finding is important to highlight, because it may provide a clue to a pathophysiologic link between depression and increased cardiovascular risk in general.

Catecholamines are thought to play a critical role in the pathophysiology of TTC, and it has been shown that plasma epinephrine and norepinephrine (NE) levels are much higher in patients with TTC than in those with Killip class III myocardial infarctions. The rather high prevalence of anxiety or depression in patients with TTC suggests either that patients with these mood disorders may develop unusually high catecholamine levels in response to emotional stress or that they may demonstrate greater cardiac sensitivity to endogenous catecholamine stimulation. With respect to patients with depression, there is evidence that both may be the case. Depressed individuals show an exaggerated NE response to emotional stress. In addition, some depressed patients have extraordinarily high cardiac sympathetic activity. Barton et al found that cardiac NE spillover, an estimate of cardiac sympathetic activity, demonstrated a bimodal distribution in those with major depressive disorder (MDD). Patients with co-morbid MDD and panic disorder had unusually high NE spillover, although those with panic disorder as a solitary diagnosis do not demonstrate this finding. Barton et al also showed that patients with MDD demonstrated reduced cardiac neuronal NE reuptake. This abnormality would allow NE to persist in the synaptic space and augment the cardiac sympathetic response. As a result, the hearts of depressed patients could be sensitized to the effects of sympathetic stimulation.

The “double whammy” of unusually high catecholamine responses and greater cardiac sympathetic sensitivity may place patients with depression at particular risk for developing TTC when exposed to stressful life experiences. This may also provide an explanation for the greater susceptibility of those with MDD to cardiac events more generally.