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Psychiatry Research
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Linkage between cardiovascular diseases and major depression: Contribution of platelet cells
Since one of thefirst reports were published in 1979 by A. Weeke, reporting an increase in cardiovascular deaths in patients suffering from major depression and manic depressive disease (Weeke, 1979), there has been a growing interest about the linkage between cardiovascular diseases and depressive disorders. Depression and cardiovascular diseases seem to affect each other mutually. At the present time, it is known that depression is not uncommon and an important contributing factor on morbidity and mortality of patients with cardiovascular disease, and also signs and symptoms of depression may manifest itself during the course of cardiovascular diseases (Celano and Huffman, 2011). Inflammation, endothelial dysfunction, increased platelet activity and aggregation, dysfunction of autonomic nervous system are the suspected mechanisms of this relationship (Celano and Huffman, 2011; Kayhan et al., 2017).
Recently, we read the article published by Kayhan and his colleagues (Kayhan et al., 2017) with great interest, which aimed to investigate the relationship between immune system cells such as neutrophils, lymphocytes and platelets and the severity levels of major depressive disorder. In their well-defined study population, they found higher platelet-to-lymphocyte ratio (PLR) levels in patients with severe major depression than other types of depression. Although this study has some limitations due to its retrospective design and small patient population, there are several take home messages that might be gathered from these results. In this context, we would like to make additional comments about the pathogenesis of bidirectional relationship between depression and cardiovascular diseases.
The contribution of inflammation and platelet cells to the pathogenesis of acute cardiovascular diseases (Balta and Ozturk, 2015) and depression (Celano and Huffman, 2011) are well established. Activation and aggregation of platelets are important components through the development of cardiac disease. Platelets release many pro-inflammatory mediators such as thromboxanes, chemokines and cytokines, which may result with increased inflammation. Higher platelet counts may be a reflection of increased thrombocyte activation, which plays an important role for mega-karyocytic proliferation and ending with relative thrombocytosis (Akkaya et al., 2014). In addition, serotonin, which is an important neuro-transmitter implicated in the depression pathogenesis, may play an important role in cardiac disease development by binding to platelets through 5-hydroxytryptamine receptors. Increased serotonin uptake by platelets facilitates platelet development resulting with pro-coagulant activity and increased cardiovascular risk (Celano and Huffman, 2011). Besides, selective serotonin reuptake inhibitor therapy, which decreases the uptake of serotonin by platelets and consequently reduces serotonin stores in platelet cells, was shown to decrease platelet activation and aggregation in an in-vitro study (Serebruany et al., 2001). In the light of thesefindings, it is reasonable to suggest that serotonin, which is an important molecule in the pathogenesis of depression and associated with platelet aggregation, may be the key component of the cardiovascular and depressive disorder linkage.
PLR, which can be calculated easily by the division of platelet counts to lymphocyte counts, is an inexpensive test providing information about the inflammatory activity. It has been studied in various cardiovascular and oncological conditions (Balta and Ozturk, 2015; Akkaya et al., 2014). Its predictive role in major depressive disorder as demonstrated by Kayhan and his colleagues (Kayhan et al., 2017) may help to identify major depression patients who will develop cardiovascular disease in the long term, but this issue needs to be tested in further studies.
As a conclusion, the association between depression and cardiovascular disease is complex and these two diseases may involve common pa-thophysiology. Platelets are the main cells in this relationship by the contribution of serotonin molecule. As shown by Kayhan and his colleagues (Kayhan et al., 2017), platelet related biomarkers might give important information in major depression patients. Understanding the exact me-chanisms mediating the link between depression and cardiovascular diseases may help to develop new treatment modalities targeting the main pathophysiology, which leads to worse cardiac outcomes. However, more research is needed to achieve these goals.
References
Akkaya, E., Gul, M., Ugur, M., 2014. Platelet to lymphocyte ratio: a simple and valuable prognostic marker for acute coronary syndrome. Int. J. Cardiol. 177 (2), 597–598. Balta, S., Ozturk, C., 2015. The platelet-lymphocyte ratio: a simple, inexpensive and rapid prognostic marker for cardiovascular events. Platelets 26 (7), 680–681. Celano, C.M., Huffman, J.C., 2011. Depression and cardiac disease. Cardiol. Rev. 19 (3), 130–142.
Kayhan, F., Gündüz,Ş., Ersoy, S.A., Kandeğer, A., Annagür, B.B., 2017. Relationships of neutrophil–lymphocyte and platelet–lymphocyte ratios with the severity of major depression. Psychiatry Res. 247, 332–335.
https://doi.org/10.1016/j.psychres.2017.11.079
Received 22 October 2017; Received in revised form 6 November 2017; Accepted 25 November 2017 Psychiatry Research xxx (xxxx) xxx–xxx
Serebruany, V.L., Gurbel, P.A., O’Connor, C.M., 2001. Platelet inhibition by sertraline and N-desmethylsertraline: a possible missing link between depression, coronary events, and mortality benefits of selective serotonin reuptake inhibitors. Pharmacol. Res. 43 (5), 453–462.
Weeke, A., 1979. Causes of death in manic-depressives. In: Schou, M., Stromgen, E. (Eds.), Prevention and Treatment of Affective Disorders. Academic Press, London, pp. 289–299. Hayriye Mihrimah OZTURK Department of Psychiatry, Ufuk University, Faculty of Medicine, Ankara, Turkey Selcuk OZTURK*
Department of Cardiology, Ankara Education and Research Hospital, Ankara, Turkey E-mail address: selcukozturk85@hotmail.com Ertan YETKİN Department of Cardiology, Private Yenisehir Hospital, Mersin, Turkey
*Corresponding author.
Psychiatry Research xxx (xxxx) xxx–xxx
