J Psychiatry Neurosci 2014; 39(3): 189-199
Osvaldo P. Almeida, MD, PhD; Andrew H. Ford, MBBS, PhD; Leon Flicker, MBBS, PhD; Graeme J. Hankey, MBBS, MD; Bu B. Yeap, MBBS, PhD; Paula Clancy, BSc, PhD; Jonathan Golledge, MBBS, PhD
Almeida, Ford — School of Psychiatry & Clinical Neurosciences, University of Western Australia, Perth; Almeida, Ford, Flicker — WA Centre for Health & Ageing, Centre for Medical Research, University of Western Australia, Perth; Almeida, Ford — Department of Psychiatry, Royal Perth Hospital, Perth; Flicker, Hankey, Yeap — School of Medicine and Pharmacology, University of Western Australia, Perth; Flicker — Department of Geriatric Medicine, Royal Perth Hospital, Perth; Hankey — Department of Neurology, Royal Perth Hospital, Perth; Yeap — Department of Endocrinology, Fremantle Hospital, Fremantle; Clancy, Golledge — Queensland Research Centre for Peripheral Vascular Disease, School of Medicine and Dentistry, James Cook University, Townsville; Golledge — Department of Vascular and Endovascular Surgery, The Townsville Hospital, Townsville, Australia
Background: Cardiovascular diseases have been associated with depression in later life, and a potential mechanism is inhibition of angio genesis. We designed this study to determine if depression is associated with higher serum concentration of endostatin, an endogenous angiogenesis inhibitor.
Methods: We performed a cross-sectional examination of a random sample of men aged 69–86 years. Those who scored 7 or higher on the 15-item Geriatric Depression Scale were deemed depressed. We determined the concentration of serum endostatin using a reproducible assay. Other measures included age, education, body mass index, smoking, history of depression, use of antidepressants, hypertension, diabetes, coronary heart disease and stroke, high sensitivity C-reactive protein, plasma homocysteine, triglycerides and cholesterol. We used logistic regression to investigate the association between endostatin and depression, and adjusted the analyses for confounding factors.
Results: Our sample included 1109 men. Sixty-three (5.7%) men were depressed. Their serum endostatin was higher than that of nondepressed participants (p = 0.021). Men in the highest decile of endostatin had greater adjusted odds of depression (odds ratio [OR] 1.78, 95% confidence interval [CI] 1.03–3.06). A doubling of endostatin doubled the odds of depression (OR 1.93, 95% CI 1.31–2.84). The probability of depression increased with the concentration of endostatin in a loglinear fashion up to a maximum of about 20%–25%.
Limitations: The cross-sectional design limits the study’s ability to ascribe causality to the association between high endostatin and depression.
Conclusions: Serum endostatin is associated with depression in older men. It remains to be established whether correction of this imbalance is feasible and could decrease the prevalence of depression in later life.
Submitted Jan. 3, 2013; Revised Mar. 29, July 8, July 25, 2013; Accepted July 26, 2013.
Funding/Support: Funded by National Health and Medical Research Council of Australia (NHMRC) project grant numbers 279408, 379600, 403963, 513823, 540404, 634492 and 1021416. J. Golledge holds the NHMRC Practitioner Fellowship 1019921 and a Senior Clinical Research Fellowship from the Office of Health and Medical Research. The sponsors had no role in the design and conduct of the study; collection, management, analysis and interpretation of the data; or preparation, review, or approval of the manuscript.
Competing interests: None declared.
Contributors: O.P. Almeida designed the study. O.P. Almeida, L. Flicker, G.J. Hankey, P. Clancy and J. Golledge acquired the data, which O.P. Almeida analyzed. A. Ford, L. Flicker, B.B. Yeap, G.J. Hankey and J. Golledge contributed to data interpretation. O.P. Almeida and A. Ford wrote the article, which all authors reviewed and approved for publication.
Correspondence to: O.P. Almeida, School of Psychiatry & Clinical Neurosciences (M573), University of Western Australia, 35 Stirling Highway, Crawley, Perth, WA 6009, Australia; email@example.com