Biological Predictors of Response to Antidepressants

抗抑郁药反应的生物预测因子

• 批准号: 7219423
• 负责人: Ramin V. Parsey
• 金额: $ 46.79万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7219423
• 关键词: Aftercare; Amygdaloid structure; Antidepressive Agents; Binding; Biological; Biological Testing; Brain imaging; Class; Communities; Corpus striatum structure; Data; Depressed mood; Desipramine; Development; Disease remission; Dorsal; Dose; Escitalopram; Goals; Image; Individual; Intervention; Localized; Logistic Regressions; Major Depressive Disorder; Measures; Methodology; Midbrain structure; Modeling; Morbidity - disease rate; Norepinephrine; Outcome; Outcome Measure; Patients; Pharmaceutical Preparations; Pilot Projects; Positron-Emission Tomography; Rate; Selection for Treatments; Selective Serotonin Reuptake Inhibitor; Sensitivity and Specificity; Serotonin; Serotonin Receptor 5-HT1A; Statistical Models; Testing; Thalamic structure; Three-Dimensional Image; Three-Dimensional Imaging; Time; Treatment Protocols; Week; Work; base; blood pressure regulation; in vivo; inhibitor/antagonist; insight; interest; mortality; novel; postsynaptic; predictive modeling; presynaptic; putamen; response; reuptake; serotonin transporter; single episode major depressive disorder

DESCRIPTION (provided by applicant): Pharmacotherapeutic treatments are the most common intervention in the treatment of major depressive disorder (MDD). Response rates to the first antidepressant can be as low as 50-60%1 while clinically more meaningful remission rates are typically only between 20%2-35%1. Development of biological tests that would enable clinicians to select the correct class of antidepressant would significantly reduce morbidity and mortality associated with MDD by reducing the time to remission. We propose to evaluate potential biological tests that can predict remission from MDD when treated with a selective serotonin reuptake inhibitor (SSRI) and whether an individual patient is more likely to respond to a SSRI or a selective norepinephrine reuptake inhibitor (SNRI), the 2 most common classes of medication for MDD. We have shown that depressed patients have higher serotonin 1A (5-HT1A) binding potential than controls. Additionally, in a naturalistic treatment study we found MDD patients with higher 5-HT1A binding potential were less likely to remit to community based treatment. It has recently been shown that baseline serotonin transporter (5-HTT) availability in the midbrain, but not striatum3, predicts response to treatment with a SSRI.4 In our naturalistic study we show that remitters have higher 5-HTT binding potential in a regionally specific manner compared to non-remitters. The treatment protocol was not controlled in our pilot study and there were too few patients to determine if remission depended on the class of antidepressant. In this proposal, we propose to perform pretreatment positron emission tomography (PET) scans and have all patients receive a standardized treatment protocol of a SSRI followed by a SNRI in SSRI non-remitters. Escitalopram is the SSRI and desipramine the SNRI of choice because at the doses we will administer, they are highly selective for the respective transporters. We hypothesize that patients with high pre and postsynaptic 5-HT1A binding potential and low 5-HTT binding potential in the midbrain, amygdala, thalamus, and dorsal putamen will not remit to a SSRI and will remit to a SNRI. Finally, we will generate a predictive model of remission based on brain imaging outcome measures. Our overall goal is to reduce the trial and error associated with finding an effective antidepressant by using data from pre-treatment quantification of 5-HT1A receptors and 5-HTT to guide antidepressant treatment selection.

描述（由申请人提供）：药物治疗是治疗主要抑郁症（MDD）的最常见干预措施。对第一种抗抑郁药的反应率可以低至50-60％1，而临床上更有意义的缓解率通常仅在20％2-35％1之间。生物测试的开发将使临床医生能够选择正确的抗抑郁药，从而通过减少缓解时间来大大降低与MDD相关的发病率和死亡率。我们建议评估潜在的生物学测试，这些测试可以预测用选择性的5-羟色胺再摄取抑制剂（SSRI）处理MDD，以及单个患者是否更有可能对SSRI或选择性去甲肾上腺素再摄取抑制剂（SNRI）（SNRI），两种最常见的Medication Sepriation for MDD。我们已经表明，抑郁症患者的5-羟色胺1a（5-HT1A）结合潜力高于对照。此外，在一项自然治疗研究中，我们发现具有较高5-HT1A结合潜力的MDD患者不太可能屈服于社区治疗。最近已经表明，中脑但不纹状体3的基线5-羟色胺转运蛋白转运蛋白（5-HTT）可用性预测与非emitters相比，在自然主义研究中，我们的自然主义研究表明，以区域特异性的方式具有更高的5-HTT结合潜力。在我们的试点研究中，该治疗方案不受控制，患者太少，无法确定缓解是否取决于抗抑郁药的类别。在此提案中，我们建议进行预处理正电子发射断层扫描（PET）扫描，并让所有患者获得SSRI的标准化治疗方案，然后在SSRI非造物质中进行SNRI。依他普兰是SSRI和去丙胺选择的SNRI，因为在我们要服用的剂量下，它们对各自的转运蛋白具有很高的选择性。我们假设在中脑，杏仁核，丘脑和背壳质中，具有高突触前和突触后5-HT1A结合潜力和低5-HTT结合潜力的患者不会汇给SSRI，并且会汇总到SNRI中。最后，我们将基于脑成像结果指标生成一个预测模型。我们的总体目标是通过使用5-HT1A受体的预处理定量和5-HTT的数据来指导抗抑郁治疗选择，以减少与找到有效抗抑郁药有关的试验和错误。