199 Neuroendocrinology Letters ISSN 0172–780X Copyright © 2002 Neuroendocrinology Letters NEL REVIEW – HARVARD REPORT The role of stress in neurodegenerative diseases and mental disorders Tobias Esch 1,2 , George B. Stefano 1,3 , Gregory L. Fricchione 4 & Herbert Benson 1 1. The Mind / Body Medical Institute, CareGroup and Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston MA 02215, U.S.A. 2. Kliniken Essen-Mitte, Department for Internal and Integrative Medicine, 45276 Essen, GERMANY . 3. Neuroscience Research Institute, State University of New York at Old Westbury, NY 11568, U.S.A. 4. The Carter Center Mental Health Program, Atlanta GA 30307, U.S.A . Correspondence to: Tobias Esch, M.D. Mind/Body Medical Institute Beth Israel Deaconess Medical Center Harvard Medical School 110 Francis Street, Suite 1A Boston MA 02215, U.S.A. PHONE : (U.S.A.) 617-632-9548 FAX: (U.S.A.) 617-632-7383 E-MAIL : tesch@caregroup.harvard.edu Submitted: April 4, 2002 Accepted: April 6, 2002 Key words: stress; Alzheimer’s disease; multiple sclerosis; anxiety; depression; PTSD; schizophrenia; Neuroendocrinology Letters 2002; 23:199–208 pii: NEL230302R02 Copyright © Neuroendocrinology Letters 2002 Abstract OBJECTIVE : Evidence for a connection between stress and selected neurodegene- rative diseases as well as mental disorders is analyzed. Does stress cause or exacerbate related pathophysiological disease processes? METHOD : The stress phenomenon is illustrated and the impact of stress on the nervous system, neurodegenerative diseases, and mental disorders is examined. The connection between stress and the hippocampus – and its association with memory func- tions – is described. In particular, the pathophysiological significance of stress in Alzheimer’s disease, multiple sclerosis, anxiety, depression, posttraumatic stress disorder, and schizophrenia is investigated. RESULTS : Stress plays a major role in various (patho)physiological processes associated with neurodegenerative dis- eases and mental disorders. In principle, stress has the potency to exert either ameliorating or detrimental effects. The specific outcome depends on multiple variables. However, the amount of stress experienced in relation to activated physiological processes that aim at successful coping and positive adjustments (i.e., stress response) most often is overwhelming – and may thus become det- rimental in the long-term. Moreover, the hippocampus is sensitive to stress, and its involvement in neurodegeneration – in the course of stress-related dis- ease processes – may account for severe clinical disabilities (e.g., memory loss). DISCUSSION/CONCLUSION: Stress has a major impact upon neurodegenerative dis- eases and mental disorders. It plays a significant role in susceptibility, progress, and actual outcome. Also, subjective or individual differences have to be taken into account. However, stress – especially ‘adequate’ acute stress (stress that is not overwhelming) – may even improve performance/biological functions and be beneficial in certain cases.