Beyond Haemostasis and Thrombosis: Platelets in Depression and Its Co-Morbidities

Abstract

Alongside their function in primary haemostasis and thrombo-inflammation, platelets are increasingly considered a bridge between mental, immunological and coagulation-related disorders. This review focuses on the link between platelets and the pathophysiology of major depressive disorder (MDD) and its most frequent comorbidities. Platelet- and neuron-shared proteins involved in MDD are functionally described. Platelet-related studies performed in the context of MDD, cardiovascular disease, and major neurodegenerative, neuropsychiatric and neurodevelopmental disorders are transversally presented from an epidemiological, genetic and functional point of view. To provide a complete scenario, we report the analysis of original data on the epidemiological link between platelets and depression symptoms suggesting moderating and interactive effects of sex on this association. Epidemiological and genetic studies discussed suggest that blood platelets might also be relevant biomarkers of MDD prediction and occurrence in the context of MDD comorbidities. Finally, this review has the ambition to formulate some directives and perspectives for future research on this topic.

Platelet Distribution Width Is Associated with P-Selectin Dependent Platelet Function: Results from the Moli-Family Cohort Study

“…Besides its hematological link with deficient platelet production disorders, PDW has been identified as a marker of outcome or prognosis in clinically defined populations of different diseases where (thrombo)inflammation plays a role. These include cancer [13] cardiovascular disease [14,15] type 2 diabetes and metabolic syndrome [16] as well as neurological disorders [17], all conditions characterized by a (sub)clinical inflammation. The PDW relevance as a possible general marker of platelet activation remains, however, poorly defined.…”

Longitudinal association between cognitive depressive symptoms and D‐dimer levels in patients following acute myocardial infarction

“…However, as the design of our study does not allow for causal inferences, lowering D‐dimer levels, for example, by improving cardiac function, could also lower depressive mood. Such a bi‐directional view is supported by an increasing literature showing that hemostasis factors are also expressed in the brain and that they may influence brain function and mood 7,36,37 …”

“…Such a bi‐directional view is supported by an increasing literature showing that hemostasis factors are also expressed in the brain and that they may influence brain function and mood. 7 , 36 , 37 …”

Circulating Inflammation Markers Partly Explain the Link Between the Dietary Inflammatory Index and Depressive Symptoms

“… 41 Moreover, more direct biomarkers of platelet activation – which is part of the thrombo-inflammatory response – and related platelet parameters may represent another potential linking pathway, also in view of recent epidemiological and genomic findings implicating them in neuropsychiatric risk, in particular depression. 44 , 45 Another potential pathway playing such a role may be represented by gut microbiota, which has increasingly been implicated in modulating immune response and brain functions. 46 Indeed, an altered microbiota – also known as dysbiosis, a phenomenon strictly dependent on nutritional patterns - has been observed in depressed patients compared to controls (see 47 , 48 for a review).…”

“…41 Moreover, more direct biomarkers of platelet activation -which is part of the thromboinflammatory response -and related platelet parameters may represent another potential linking pathway, also in view of recent epidemiological and genomic findings implicating them in neuropsychiatric risk, in particular depression. 44,45 Another potential pathway playing such a role may be represented by gut microbiota, which has increasingly been implicated in modulating immune C Figure 1 Scatter plot of overall depressive symptoms (PHQ9-6) score vs DII. Linear interpolation of data is reported for (A) the total sample (N=13,301), (B) separate genders and (C) prevalent health conditions or use of antidepressants, along with their 95% confidence interval (grey shade).…”