Translational Studies of Depression, Platelets, & CAD

抑郁症的转化研究，血小板，

• 批准号: 7113675
• 负责人: Juan Jose Badimon
• 金额: $ 66.36万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-10 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7113675
• 关键词: antidepressants; cardiovascular disorder chemotherapy; cardiovascular disorder epidemiology; cardiovascular disorder risk; clinical research; clinical trials; cognitive behavior therapy; coronary disorder; depression; human subject; human therapy evaluation; mental disorder chemotherapy; nitric oxide; patient oriented research; platelet aggregation; platelets; questionnaires; relapse /recurrence; serotonin; serotonin inhibitor; serotonin receptor; thrombosis

DESCRIPTION (provided by applicant): Depressive symptoms significantly increase the risk of acute coronary syndromes recurrence (ACS). Platelet-thrombus formation over a disrupted atherosclerotic plaque is fundamental for ACS recurrence.Serotonin (5-HT) is an important stimulant of platelet reactivity. Increased 5-HT-mediated platelet reactivity due to upregulation of the platelet 5-HT2A receptor, increases thrombosis formation and has been postulated to a major mechanism linking depression to ACS recurrence. It is not known at this time if depression interventions reverse the increased risk of ACS events in depressed patients. The selective serotonin reuptake inhibitors (SSRIs) and the 5-HT2A receptor antidepressants improve depressive symptoms at equal rates. Both types of antidepressants may attenuate platelet reactivity by improving depressive symptoms (CNS mediated indirect effects). However, the SSRIs and the 5-HT2A receptor antagonists may have additional but divergent pharmacologic effects on platelet reactivity (direct platelet effects). Given the relationship between depression, platelet-thrombus formation, and the ACS, those antidepressants capable not only of improving depression symptoms but also of inhibiting platelet reactivity directly, may have the greatest net (direct + indirect) impact in inhibiting platelet-thrombus formation and preventing ACS events. A cross-sectional, case-control study will be conducted to compare 5-NT-mediated platelet reactivity and thrombosis between depressed and non-depressed patients with coronary artery disease (CAD) history. The direct in vitro effects of the SSRIs and 5-HT2A receptor antagonists will also be assessed. A randomized, 3 active arm, 1 control arm, depression intervention trial will be conducted to compare the in vivo net effects of pharmacologic (the SSRIs and 5-HT2A receptor antagonists) treatment and the indirect effects of a non-pharmacologic (cognitive behavioral therapy) treatment on platelet reactivity and thrombosis in depressed CAD patients. By defining differences in direct-platelet, CNS-mediated indirect, and net effects on platelet reactivity and thrombus formation, depression interventions that are best at inhibiting platelet reactivity and thrombogenicity can then be tested for reducing cardiovascular morbidity and mortality.

描述（由申请人提供）：抑郁症状显着增加急性冠脉综合征复发（ACS）的风险。破裂的动脉粥样硬化斑块上的血小板血栓形成是 ACS 复发的基础。血清素 (5-HT) 是血小板反应性的重要刺激剂。由于血小板 5-HT2A 受体上调，5-HT 介导的血小板反应性增加，增加血栓形成，并被认为是抑郁症与 ACS 复发之间联系的主要机制。 目前尚不清楚抑郁症干预措施是否可以逆转抑郁症患者发生 ACS 事件的风险增加。选择性血清素再摄取抑制剂 (SSRI) 和 5-HT2A 受体抗抑郁药以相同的速度改善抑郁症状。两种类型的抗抑郁药都可以通过改善抑郁症状（中枢神经系统介导的间接作用）来减弱血小板反应性。然而，SSRIs 和 5-HT2A 受体拮抗剂可能对血小板反应性具有额外但不同的药理作用（直接血小板作用）。鉴于抑郁症、血小板血栓形成和 ACS 之间的关系，那些不仅能够改善抑郁症状而且能够直接抑制血小板反应性的抗抑郁药，可能在抑制血小板血栓形成和预防 ACS 事件方面具有最大的净（直接+间接）影响。 将进行一项横断面病例对照研究，以比较有冠状动脉疾病 (CAD) 病史的抑郁症和非抑郁症患者之间 5-NT 介导的血小板反应性和血栓形成。还将评估 SSRI 和 5-HT2A 受体拮抗剂的直接体外作用。将进行一项随机、3 个主动组、1 个对照组、抑郁干预试验，以比较药物（SSRI 和 5-HT2A 受体拮抗剂）治疗的体内净效应和非药物（认知行为治疗）治疗对抑郁 CAD 患者血小板反应性和血栓形成的间接影响。通过定义直接血小板、中枢神经系统介导的间接效应和对血小板反应性和血栓形成的净效应的差异，可以测试最能抑制血小板反应性和血栓形成的抑郁症干预措施，以降低心血管发病率和死亡率。

项目成果

Anxiety is a better predictor of platelet reactivity in coronary artery disease patients than depression.

• DOI: 10.1093/eurheartj/ehp602
• 发表时间: 2010-07
• 期刊: European heart journal
• 影响因子: 39.3
• 作者: M. U. Zafar;M. Paz-Yepes;D. Shimbo;G. Vilahur;M. Burg;M. Burg;W. Chaplin;V. Fuster;K. Davidson;J. Badimón