Blood platelets, due to shared biochemical and functional properties with presynaptic serotonergic neurons, constituted, over the years, an attractive peripheral biomarker of neuronal activity. Therefore, the literature strongly focused on the investigation of eventual structural and functional platelet abnormalities in neuropsychiatric disorders, particularly in depressive disorder. Given their impact in biological psychiatry, the goal of the present paper was to review and critically analyze studies exploring platelet activity, functionality, and morpho-structure in subjects with depressive disorder.

According to the PRISMA guidelines, we performed a systematic review through the PubMed database up to March 2020 with the search terms: (1) platelets in depression [Title/Abstract]”; (2) “(platelets[Title]) AND depressive disorder[Title/Abstract]”; (3) “(Platelet[Title]) AND major depressive disorder[Title]”; (4) (platelets[Title]) AND depressed[Title]”; (5) (platelets[Title]) AND depressive episode[Title]”; (6) (platelets[Title]) AND major depression[Title]”; (7) platelet activation in depression[All fields]”; and (8) platelet reactivity in depression[All fields].”

After a detailed screening analysis and the application of specific selection criteria, we included in our review a total of 106 for qualitative synthesis. The studies were classified into various subparagraphs according to platelet characteristics analyzed: serotonergic system (5-HT2A receptors, SERT activity, and 5-HT content), adrenergic system, MAO activity, biomarkers of activation, responsivity, morphological changes, and other molecular pathways.

Despite the large amount of the literature examined, nonunivocal and, occasionally, conflicting results emerged. However, the findings on structural and metabolic alterations, modifications in the expression of specific proteins, changes in the aggregability, or in the responsivity to different pro-activating stimuli, may be suggestive of potential platelet dysfunctions in depressed subjects, which would result in a kind of hyperreactive state. This condition could potentially lead to an increased cardiovascular risk. In line with this hypothesis, we speculated that antidepressant treatments would seem to reduce this hyperreactivity while representing a potential tool for reducing cardiovascular risk in depressed patients and, maybe, in other neuropsychiatric conditions. However, the problem of the specificity of platelet biomarkers is still at issue and would deserve to be deepened in future studies.

由于与突触前血清素能神经元具有共同的生化和功能特性，血小板多年来构成了神经元活动的有吸引力的外周生物标志物。因此，文献强烈关注神经精神疾病，特别是抑郁症中最终的结构和功能性血小板异常的调查。鉴于它们对生物精神病学的影响，本文的目的是回顾和批判性地分析探索抑郁症患者血小板活性、功能和形态结构的研究。

根据 PRISMA 指南，我们通过 PubMed 数据库对截至 2020 年 3 月的搜索词进行了系统评价：（1）抑郁症中的血小板 [标题/摘要] ”；(2) “ （血小板[标题]）和抑郁症[标题/摘要]”；(3) “（血小板[标题]）和重度抑郁症[标题]”；(4) (platelets[Title]) AND 抑郁[Title]”；（5）（血小板[标题]）和抑郁发作[标题]”；（6）（血小板[标题]）和重度抑郁症[标题]”；(7)抑郁症中的血小板活化[所有领域]”；(8)抑郁症中的血小板反应性[所有领域]。”

经过详细的筛选分析和特定选择标准的应用，我们在我们的审查中总共纳入了 106 个进行定性综合。根据所分析的血小板特征将研究分为不同的小段：5-羟色胺能系统（5-HT 2A受体、SERT 活性和 5-HT 含量）、肾上腺素能系统、MAO 活性、活化的生物标志物、反应性、形态学变化和其他分子途径。

尽管检查了大量的文献，但还是出现了不明确的，有时甚至是相互矛盾的结果。然而，关于结构和代谢改变、特定蛋白质表达的改变、聚集性的改变或对不同促激活刺激的反应性的发现可能暗示抑郁症受试者潜在的血小板功能障碍，这将导致一种过度反应的状态。这种情况可能会导致心血管风险增加。根据这一假设，我们推测抗抑郁药治疗似乎可以减少这种过度反应，同时代表了降低抑郁症患者心血管风险的潜在工具，也许还有其他神经精神疾病。然而，