Contents lists available at ScienceDirect Maturitas journal homepage: www.elsevier.com/locate/maturitas The link between depression and atherosclerosis through the pathways of inflammation and endothelium dysfunction Christina Chrysohoou a, ⁎ , Natasa Kollia b , Dimitris Tousoulis a a First Cardiology Clinic, School of Medicine, University of Athens, Athens, Greece b Department of Nutrition & Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece ARTICLE INFO Keywords: Depression Cardiovascular disease Mechanisms ABSTRACT A large body of evidence suggests that depression increases the risk of cardiovascular morbidity and mortality. The elevated risk associated with depression is not limited to clinical major depressive disorder but also extends to sub-syndromal depressive symptoms and constructs with overlapping characteristics, such as vital exhaustion. Multiple pathophysiological pathways are involved in the relationship between depressive symptoms and atherosclerosis and its clinical manifestations and progression. These underlying mechanisms are not yet fully understood and need further clarification. This review examines inflammation and endothelium dysfunction as potential biological factors involved in the relationship between depressive symptoms and atherosclerosis. It has been reported that systemic inflammation and psychological factors interact through complex pathophysiolo- gical and behavioral mechanisms and one question that has been raised concerns whether the inflammation drives depression or vice versa, or whether the association is merely coincidental. Although further investigation is needed, including well-designed prospective studies, to address this question thoroughly, it seems that there is a feedback relationship, although the biological pathways of each direction may be distinct. 1. Introduction Depression is a serious public health concern, estimated to affect 350 million people worldwide, mainly women and older adults [1–3]. Atherosclerosis and depression are listed between the four more common medical conditions related to increased mortality and mor- bidity [4]; in particular, the World Health Organization has ranked atherosclerosis as the 1 st leading cause and depression the 4th leading cause of disability worldwide and projects that by 2030, depression will be the first cause. The fact that depressive disorders are more frequently characterize women and older people, in which cardiovascular disease is often underestimated and or not well managed, highlight the need for effective preventive actions in the aforementioned groups of in- dividuals. There is a significant scientific body of evidence linking de- pression with atherosclerosis through various pathways, mainly through unhealthy lifestyle behaviours and neuro-hormonal system activation. However, the exact patho-biological mechanisms are not well understood and appreciated. Thus, the scope of this review was to illustrate pathophysiological pathways of depression on endothelial function and vascular pathology, which act as surrogate markers of atherosclerotic disease. 2. Methothology A mini-review of the relevant studies performed over the time period January 2000–October 2017 was conducted in order to sum- marize the mechanisms underlying the depression-atherosclerosis as- sociation focusing on the role of inflammation and endothelial dys- function. A literature search was conducted in October 2017. The Plumbed database was used by applying the following title keyword search terms and their combinations: depression OR depressive AND atherosclerosis OR cardiovascular AND endothelium OR endothelial OR inflammation OR inflammatory; limited to studies published as journal articles in the English language. The reference lists of these manuscripts were then examined for additional titles; and the most relevant manuscripts were selected for citation based on the predetermined subheadings of the review. Reviews and meta-analyses were preferred. A narrative sum- mary of the findings of these studies is provided. 2.1. Depression and atherosclerosis Depression is a common mental disorder, which is currently the leading cause of disability worldwide, and is a major contributor to the https://doi.org/10.1016/j.maturitas.2017.12.001 Received 17 November 2017; Received in revised form 26 November 2017; Accepted 1 December 2017 ⁎ Corresponding author at: 46 Paleon Polemiston St., Glyfada, 166 74, Attica, Greece. E-mail address: chrysohoou@usa.net (C. Chrysohoou). Maturitas 109 (2018) 1–5 0378-5122/ © 2017 Elsevier B.V. All rights reserved. T