Vascular risk factors for depression and apathy | Part 1 54 Discussion In older persons without preexistent cardiac disease, depression only predicts the onset of stroke over a 9-year follow-up in case of low neuroticism scores. Although we did not directly measure the level of subclinical vascular disease with imaging techniques, this finding may be explained by the presence of subclinical cardiovascular as well as cerebrovascular disease for the following reasons. Atherosclerosis generally develops over years, with the ultimate outcome of a cardiac or cerebrovascular event 31. Nonetheless, subclinical vascular disease is also associated with (specific) depressive symptoms 11. In case atherosclerosis first gives rise to an increased depressive symptom score, depression will emerge as a predictor for stroke in observational cohort studies. How does this theory fit with our results? First, our finding that depression increases the risk for stroke in patients with cardiac disease is in line with the theory that depressive symptoms in this population partly reflect the severity of underlying subclinical vascular disease 5 8. In people without preexisting cardiac disease, neuroticism may be assumed to be the most important pathway to depression (neurotic depression) 32. Nonetheless, in this group, several persons have low neuroticism scores that by definition cannot have contributed to their depression. In this group, depressive symptoms may be a sign (or epiphenomenon) of subclinical vascular disease. Indeed, this hypothesis fits with our finding that depression in the presence of low neuroticism scores predicts the onset of stroke in persons without manifest cardiac disease. The interplay among neuroticism, vascular disease, and depression is complex. Crosssectional studies show that the association between depression and neuroticism is weaker in patients with vascular disease 32 33. Prospective studies studying the effect of neuroticism and depression on the incidence of stroke in concert are lacking. Nonetheless, some studies suggest that high levels of neuroticism may increase risk of vascular events. In the Swedish Twin Register, neuroticism predicted the development of coronary heart disease over 25 years of follow-up, but significance was lost after controlling for familial influences 34. In the UK Health and Lifestyle Survey, neuroticismpredicted cardiacmortality, but not death from stroke 35. In the Chicago Health and Aging Project, a psychosocial composite score including items of neuroticism was associated with an increased risk on stroke over and above the classical vascular risk factors for stroke 36. As this composite score also included depression, perceived stress, and life dissatisfaction, the net effect of neuroticism remains unknown. It is most likely that neuroticism by itself is not related to vascular health, as was found in our study. Three limitations should be taken into account. First, there was a selective dropout at baseline, as persons with missing neuroticism scores were more depressed and more vascular comprised. This might have reduced the power of the results in the cardiac subgroup, in which no differential impact of depression by neuroticism status could be demonstrated. Effects for the noncardiac subgroup are difficult to estimate, but most likely, results are conservative.
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