Immune System Activation

Advances in biologic psychiatry have included the discovery of numerous neurochemical, neuroendocrine, and neuroanatomic alterations in unipolar depression, some of which likely contribute to the increased vulnerability of depressed patients to CVD. These biologic changes include immune-system activation with increased secretion of proinflammatory cytokines, endothelial dysfunction, hypothalamic-pituitaryadrenocortical (HPA) system and sympathoadrenal hyperactivity, diminished heart rate variability, alterations in platelet receptors and/or reactivity, and ventricular instability and myocardial ischemia in reaction to mental stress (Fig. 96–1). Evidence further suggests that the relationship between inflammation and autonomic dysfunction is more robust among depressed patients than nondepressed counterparts. And most recently, a candidate gene study suggested that genetic variation related to endothelial dysfunction is predictive of depressive symptoms in patients with cardiovascular disease. Taken together, these findings support the premise that genetic, biologic, and behavioral factors interact in a complex and not as yet fully defined, multidirectional fashion that ultimately links depression and cardiovascular disease.