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NEUROLOGY 2008;70:788-794
© 2008 American Academy of Neurology

Psychological distress, major depressive disorder, and risk of stroke

P. G. Surtees, PhD, N.W.J. Wainwright, PhD, R. N. Luben, BSc, N. J. Wareham, MBBS, PhD, S. A. Bingham, PhD and K.-T Khaw, MBBChir

From Strangeways Research Laboratory and University of Cambridge Department of Public Health and Primary Care (P.G.S., N.W.J.W., R.N.L.), Worts Causeway; MRC Epidemiology Unit (N.J.W.), Elsie Widdowson Laboratories; Medical Research Council Dunn Nutrition Unit (S.A.B.); Medical Research Council Centre for Nutritional Epidemiology in Cancer Prevention and Survival (S.A.B.), Department of Public Health and Primary Care; and Clinical Gerontology Unit (K.-T.K.), University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Cambridge, UK.

Address correspondence and reprint requests to Dr. Paul Surtees, Strangeways Research Laboratory, Worts Causeway, Cambridge, CB1 8RN, UK paul.surtees{at}srl.cam.ac.uk

Background: Studies have suggested that mood status is associated with an increased risk of stroke, though mostly based on measures of depression defined by symptoms alone rather than diagnostic criteria representative of clinically important distress and impairment. We investigated this association based upon a large population-based prospective cohort study.

Methods: Baseline assessment of major depressive disorder (MDD) and of mental health well-being (defined by the Mental Health Inventory, MHI-5) was completed by 20,627 stroke-free participants, aged 41 to 80 years, in the United Kingdom European Prospective Investigation into Cancer–Norfolk study.

Results: During 8.5 years of follow-up, 595 incident (fatal and nonfatal) stroke endpoints were recorded. Neither past year nor lifetime MDD was associated with stroke. A one SD decrease in MHI-5 scale score (representing greater emotional distress) was associated with an 11% increased risk of stroke after adjustment for age, sex, cigarette smoking, systolic blood pressure, cholesterol, obesity, preexisting myocardial infarction, diabetes, social class, education, hypertension treatment, family history of stroke, and antidepressant medication use (hazard ratio 1.11, 95% CI 1.00 to 1.22). This association was consistent for men and for women, for fatal and nonfatal stroke, and conformed to a dose-response relationship.

Conclusions: Findings from this large prospective cohort study suggest that increased psychological distress is associated with elevated stroke risk. Episodic major depressive disorder was not associated with incident stroke in this study.

Abbreviations: BMI = body mass index; DSM-IV = Diagnostic and Statistical Manual of Mental Disorders, 4th edition; EPIC = European Prospective Investigation into Cancer; GAD = generalized anxiety disorder; HLEQ = Health and Life Experiences Questionnaire; ICD = International Classification of Diseases; MDD = major depressive disorder; MHI-5 = Mental Health Inventory; MI = myocardial infarction; SBP = systolic blood pressure; SF-36 = Short Form 36.


EPIC-Norfolk is supported by program grants from the Medical Research Council UK (G9502233, G0300128) and Cancer Research UK (C865/A2883) with additional support from the European Union, Stroke Association, British Heart Foundation, Department of Health, and the Wellcome Trust.

Disclosure: The authors report no conflicts of interest.

Received June 21, 2007. Accepted in final form September 12, 2007.




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