In addition, evidence has been reviewed suggesting that SSRI treatment may possibly reduce this medical morbidity and mortality. What has not been discussed is what drives these associations. It is important to make a number of distinctions. There are undoubtedly multiple pathways connecting depression and heart disease, and although some pathways may operate in both

medically healthy depressed patients and in those with pre-existing cardiac disease, some could be unique to one situation or the other. In addition, the mechanisms that lie behind the reduction in risk with SSRIs (if that reduction is confirmed), may also not be exactly the same as the mechanism Inhibitors,research,lifescience,medical that created the risk. Multiple mechanisms linking depression and heart disease have been suggested. Depression has regularly been demonstrated Inhibitors,research,lifescience,medical to lower adherence to prescribed medication and secondary prevention measures34,35 among cardiac patients. ABT263 Studies of noradrenergic activity,36 autonomic activity,37,38 heart rate variability (HRV),39,40 and Inhibitors,research,lifescience,medical platelet biomarkers,41-43 as well as inflammatory markers,43-46 have regularly found differences in clinically depressed compared with nondepressed post-MI patients that favor the development of heart disease. Levels of omega-3 fatty

acids are known to vary between depressed and nondepressed populations and influence the risk of ischemic heart disease.47 The possibility also exists that depression and vascular disease share Inhibitors,research,lifescience,medical certain vulnerability genes.48 However, why depression and heart disease are so closely associated is far from clear. A detailed discussion of each of these potential mechanisms is beyond the scope of this review, but recent references are supplied.49,50 Although not as immediately obvious as the question of potential mechanisms, a very important issue is that of when these mechanisms come into play. The relationship between depression and heart disease that has been documented is an association.

Associations do not explain causality, and can result Inhibitors,research,lifescience,medical from multiple different pathways. Certainly some of the depressive symptomatology and even some of the major depression that arises for the first time following a coronary event is a reaction to that medical PD184352 (CI-1040) event. However, there is considerable evidence that such cases are not an explanation for most of the association between depression and heart disease. Two different pieces of information are pertinent. Earlier in this review it was mentioned that the 1993 study by Anda was the first epidemiological study to control for cardiac risk factors. It was also the first study to carefully control for prior medical illness.10 It was based on a follow-up of the National Health and Human Nutrition Examination Survey (NHANES) and involved over 3000 individuals collected at that time for more than 13 years.