Charting the perfect storm: emerging biological interfaces between stress and stroke.

A growing body of evidence demonstrates that psychosocial stress is an important and often underestimated risk factor for cardiovascular disease such as myocardial infarction and stroke. In this article, we map out major biological interfaces between stress, stress-related psychiatric disorders, and stroke, placing special emphasis on the fact that stress and psychiatric disorders may be both cause and consequence of cardiovascular disease. Apart from high-risk lifestyle habits such as smoking and lack of exercise, neuroendocrine dysregulation, alterations of the hemostatic system, increased oxidative stress, and inflammatory changes have been implicated in stress-related endothelial dysfunction. Heart rate provides another useful and easily available measure that reflects the complex interplay of vascular morbidity and psychological distress. Importantly, heart rate is emerging as a valuable predictor of stroke outcome and, possibly, even a target for therapeutic intervention. Furthermore, we review recent findings highlighting the role of FK506-binding protein 51 (FKBP5), a co-chaperone of the glucocorticoid receptor, and of perturbations in telomere maintenance, as potential mediators between stress and vascular morbidity. Finally, psychiatric sequelae of cardiovascular events such as post-stroke depression or posttraumatic stress disorder are highly prevalent and may, in turn, exert far-reaching effects on recovery and outcome, quality of life, recurrent ischemic events, medication adherence, and mortality.