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.

Keywords: cardiovascular disease; depression; gender; neurodegenerative disorders; platelet distribution width; platelets; psychiatric comorbidities.

Figure 1

Shared platelet functionality between cardiovascular and neurological disease. Activation of platelets via specific receptors, signaling cascades and degranulation allows platelets to enhance tissue inflammation and to stimulate thrombotic complications, initiating and aggravating cardiovascular malfunction. A number of specific mediators of neurological disease are also capable of influencing platelet function and platelet activation appears to be linked to the development of those neurological and psychiatric diseases, in essence attributed to brain degeneration, i.e., markers of platelet activation may reflect the stage of mental disease progress. Several of these mediators are encoded by genes whose (epi)genetic variability has been involved in both cardiovascular and mental disease. Hence, various comorbidities of cardiovascular and mental disease may occur, because of the involvement of platelets in both disorders. Therefore, commonly measured indices of platelet mass, number and their activation, which are useful to characterize platelet functionality, seem useful biomarkers of the platelet concomitant involvement in both cardiovascular and neurological disorders. Plt: platelet count, MPV: mean platelet volume, PDW: platelet distribution width, MDD: major depressive disorder, AD: Alzheimer’s disease, PD: Parkinson disease, ALS: amyotrophic lateral sclerosis. Images of non-activated/activated and aggregated platelets were modified with permission from ref. [315] and [316], respectively.

Figure 2

PDW: a novel potential biomarker for depression, its neurodegenerative and psychiatric comorbidities. Platelet distribution width (PDW) represents and index of platelet volume variability in a subject. It has been associated with both depressive symptoms and major depression, but also with neurodegenerative and psychiatric comorbidities like Alzheimer’s disease, mild cognitive impairment, attention deficit hyperactivity disorder and panic disorder. Beyond epidemiological evidence, genomic studies identified consistent co-heritability based on common genetic variants between PDW and depression, as well as between PDW and Parkinson disease risk. Overall, this evidence suggests PDW as a very promising candidate biomarker for MDD and its comorbidities to investigate in the future.