DEPRESSION GETS OLD FAST: DO STRESS AND DEPRESSION ACCELERATE CELL AGING?

Depression has been likened to a state of "accelerated aging," and depressed individuals have a higher incidence of various diseases of aging, such as cardiovascular and cerebro vascular diseases, metabolic syndrome, and dementia. Chronic exposure to certain interlinked biochemical pathways that mediate stress-related depression may contribute to "accelerated aging," cell damage, and certain comorbid medical illnesses. Biochemical mediatory explored in this theoretical review include the hypothalamic-pituitary-adrenal axis (e.g., hyperor hypoactivation of glucocorticoid receptors), neurosteroids, such as dehydroepiandrosterone and allopregnanolone, brain-derived neurotrophic factor excitotoxicity, oxidative and inflammatory stress, and disturbances of the telomere/telomerase maintenance system. A better appreciation of the role of these mediators in depressive illness could lead to refined models of depression, to a re-conceptualization of depression as a whole body disease rather than just a "mental illness," and to the rational development of new classes of medications to treat depression and its related medical comorbidities. Depression and Anxiety 27:327-338, 2010. (C) 2010 Wiley-Liss, Inc.