SSRI-reduced platelet reactivity in non-responding patients with life-long Recurrent Depressive Disorder: Detection and involved mechanisms

Aleksovski, Boris; Neceva, V.; Vujovic, V.; Manusheva, Nensi; Rendevski, Vladimir; Novotni, Antoni; Filipce, Ana; Spasovska, Anastazija; Sofijanova, Aspazija; Aleksovski, Vasko; Gjorgoski, Icko

doi:10.1016/j.thromres.2018.03.006

Cited by 12 publications

(10 citation statements)

References 38 publications

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“…This association was quite robust across varying p-value thresholds (P T ranging from 0.001 to 1.0; Figure 1). Overall, the evidence reported here suggests PDW as a new potential biomarker for Parkinson's disease and is consistent with previous studies reporting positive associations between PDW and depression risk and/or symptoms, both at the epidemiological level (17,24) and at the genetic level (16). Indeed, depression represents one of the main non-motor symptoms of PD, often presenting in its prodromal phase (25), and shows progressive patterns of microglial activation like other neurodegenerative disorders (26).…”

Section: Resultssupporting

confidence: 91%

Assessing Genetic Overlap Between Platelet Parameters and Neurodegenerative Disorders

et al. 2020

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Neurodegenerative disorders such as Parkinson's disease (PD) and Alzheimer's disease (AD) suffer from the lack of risk-predictive circulating biomarkers, and clinical diagnosis occurs only when symptoms are evident. Among potential biomarkers, platelet parameters have been associated with both disorders. However, these associations have been scarcely investigated at the genetic level. Here, we tested genome-wide coheritability based on common genetic variants between platelet parameters and PD/AD risk, through Linkage Disequilibrium Score Regression. This revealed a significant genetic correlation between platelet distribution width (PDW), an index of platelet size variability, and PD risk (r g [SE] = 0.080 [0.034]; p = 0.019), which was confirmed by a summarysummary polygenic score analysis, where PDW explained a small but significant proportion PD risk (<1%). AD risk showed no significant correlations, although a negative trend was observed with PDW (rg [SE] =-0.088 [0.053]; p=0.096), in line with previous epidemiological reports. These findings suggest the existence of limited shared genetic bases between PDW and PD and warrant further investigations to clarify the genes involved in this relation. Additionally, they suggest that the association between platelet parameters and AD risk is more environmental in nature, prompting an investigation into which factors may influence these traits.

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Section: Resultssupporting

confidence: 91%

Assessing Genetic Overlap Between Platelet Parameters and Neurodegenerative Disorders

et al. 2020

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“…Although a direct link between PDW variability and platelet function has not yet been fully established [149], this evidence suggests once again that lower platelet activation and function may be a feature of depression, along with lower platelet and blood plasma serotonin, and lower platelet reactivity. Moreover, studies on collagen-and epinephrine-induced aggregation and the percentage of spiny and discoid platelets also suggested a lower platelet reactivity as a potential feature of depression [148]. In line with this evidence, in a comprehensive analysis of the relation between low-grade inflammation and mental health in a large Italian population cohort (the Moli-sani study; N = 12,732), our group identified a significant positive association between continuous depressive symptoms and PDW [150].…”

Section: Epidemiological Studiessupporting

confidence: 78%

“…Platelet parameters have also been studied with reference to MDD treatments: in a small study comparing 15 MDD patients under escitalopram therapy-one of the most used SSRI treatments-and 17 healthy controls, treated patients exhibited a significant reduction in both MPV and Plt, which were instead higher than in controls at baseline [147]. Another study comparing 31 patients with life-long recurrent depression treated with SSRIs and 31 matched healthy controls, reported significantly higher MPV, platelet distribution width (PDW, an index of size variability of circulating platelets) and platelet-to-larger cell ratio (P-LCR; i.e., the proportion of large platelets with volume >12 fL, which represents an index of platelet size useful in the diagnosis of thrombocytopenia) in depressed participants [148]. Although a direct link between PDW variability and platelet function has not yet been fully established [149], this evidence suggests once again that lower platelet activation and function may be a feature of depression, along with lower platelet and blood plasma serotonin, and lower platelet reactivity.…”

Section: Epidemiological Studiesmentioning

confidence: 99%

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

Izzi

Tirozzi

Cerletti

et al. 2020

IJMS

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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.

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“…However, they have negative impacts on osteoblasts. The SSRI was the first class of antidepressant drugs discovered by scientists [2]. The mechanism of action of SSRI is to block the reuptake of serotonin to increase its concentration at the central level.…”

Section: Introductionmentioning

confidence: 99%

The effects of serotonin inhibitors on bone metabolism: literature review

Franco¹,

Matteo²,

Gianfreda³

et al. 2020

jos

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Depression is a mood and behavior disorder. It is a very frequent pathology in the world that requires pharmacological treatment using drugs that inhibit the recovery of serotonin. In fact, serotonin is a hormone that creates a feeling of well-being at the level of central nervous system. Serotonin is mainly produced by nerve cells. Therefore, selective serotonin reuptake inhibitors (SSRIs) are mainly used for the treatment of states of anxiety and major depressive disorder. SSRIs increase serotonin level, blocking its resorption in the presynaptic cell. Consequently, an increase in the bioavailability of serotonin in the synaptic junction occur. In fact, at the bone level, according to some observations, it causes an increase in bone resorption. Our study with a systematic review of the literature was to evaluate whether the intake of SSRIs could in any way influence implant survival. "SSRI" and "dental implant" were used as key words in the principal resources. Five articles that met the inclusion criteria were considered. The study found that these drugs can affect the implant survival rate. The data of these articles concerning implant survival have extrapolated. There is an association between intake and implant survival, probably due to a possible link between bone metabolism and drug. Further studies are recommended to effectively evaluate the influence of the drug on implant survival.

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SSRI-reduced platelet reactivity in non-responding patients with life-long Recurrent Depressive Disorder: Detection and involved mechanisms

Cited by 12 publications

References 38 publications

Assessing Genetic Overlap Between Platelet Parameters and Neurodegenerative Disorders

Assessing Genetic Overlap Between Platelet Parameters and Neurodegenerative Disorders

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

The effects of serotonin inhibitors on bone metabolism: literature review

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