SPECT Brain Imaging as a Biomarker of Major Depression

SPECT 脑成像作为重度抑郁症的生物标志物

• 批准号: 6983491
• 负责人: JAY D AMSTERDAM
• 金额: $ 20.21万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-30 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6983491
• 关键词: biomarker; brain disorder diagnosis; brain imaging /visualization /scanning; citalopram; clinical research; clinical trials; dopamine receptor; dopamine transporter; drug screening /evaluation; human subject; human therapy evaluation; interview; major depression; mental disorder chemotherapy; occipital lobe /cortex; outcomes research; pathologic process; pharmacokinetics; radionuclide diagnosis; radiotracer; receptor binding; receptor expression; single photon emission computed tomography; statistics /biometry; biomarker; brain disorder diagnosis; brain imaging /visualization /scanning; citalopram; clinical research; clinical trials; dopamine receptor; dopamine transporter; drug screening /evaluation; human subject; human therapy evaluation; interview; major depression; mental disorder chemotherapy; occipital lobe /cortex; outcomes research; pathologic process; pharmacokinetics; radionuclide diagnosis; radiotracer; receptor binding; receptor expression; single photon emission computed tomography; statistics /biometry

DESCRIPTION (provided by applicant): Dopamine (DA) may play a key role in the pathophysiology of major depressive episode (MDE) and may, in part, mediate the therapeutic action of many antidepressant drugs. Recent animal and human studies suggest that DA transporter (DAT) activity may reflect the general state of DA neurotransmitter activity in the CNS, and alterations in normal DAT activity may reflect alteration in central DA function. A variety of antidepressants affect central DA activity, and this effect is not limited to 'DA-ergic' antidepressants. Studies have shown that repeated administration of antidepressants from all pharmacological classes result in enhanced D2-like receptor binding, and this enhanced sensitization has been suggested as a 'final common pathway' for antidepressant action. [99mTc]TRODAT-1 is a unique SPECT radioligand which is highly selective for the DAT with almost no SERT cross binding. Studies with [99mTc]TRODAT-1 conducted at Penn have shown it to be an effective tool for evaluating alterations in striatal DAT levels. Preliminary studies in patients with Parkinson's disease (compared to healthy controls) have shown [99mTc]TRODAT-1 to be effective for quantifying DAT levels. Preliminary studies from our group have shown a significant increase (12% - 36%) in [99mTc]TRODAT-1 binding to DAT sites in the putamen and caudate regions of patients with MDE compared to controls. We propose to conduct a preliminary study to examine whether increased striatal DAT levels in MDE represent a putative state-dependent biomarker of depression. For specific aim #1 we will ask: Do increased striatal DA T levels in MDE represent a state-dependent biomarker that is reduced after successful antidepressant treatment? We hypothesize that increased striatal DAT levels in MDE patients will decrease during successful antidepressant treatment, and will not appreciably decrease in patients who do not respond to treatment. For specific aim #2 we will ask: Do striatal DAT levels remain stable over time in non-depressed, healthy controls? To answer these questions, we will measure striatal DAT levels using [99mTc]TRODAT-1 SPECT with MRI co-localization, before and after 8 weeks of treatment with s-citalopram or placebo in 44 drug-naive MDE patients. We will compare these results to measurements of striatal DAT levels in 22 non-depressed, healthy subjects studied under similar conditions with [99mTc]TRODAT-1 SPECT on two separate occasions 8 weeks apart.

描述（由申请人提供）：多巴胺（DA）可能在主要抑郁发作（MDE）的病理生理学中起关键作用，并且可能部分介导了许多抗抑郁药的治疗作用。 最近的动物和人类研究表明，DA转运蛋白（DAT）活性可能反映了中枢神经系统中DA神经递质活性的一般状态，正常DAT活性的改变可能反映了中央DA功能的改变。多种抗抑郁药会影响中心DA活性，并且这种作用不仅限于“ DA-ergic”抗抑郁药。 研究表明，从所有药理类别中重复施用抗抑郁药会导致D2样受体结合增强，并且已提出这种增强的敏化作用是用于抗抑郁作用的“最终共同途径”。 [99MTC] Trodat-1是一种独特的SPECT放射线，对于几乎没有SERT交叉结合的DAT具有高度选择性。在Penn进行的[99MTC] Trodat-1的研究表明，它是评估纹状体DAT级别改变的有效工具。 对帕金森氏病（与健康对照组相比）的患者的初步研究表明，[99MTC] Trodat-1可以有效地量化DAT水平。与对照组相比，我们小组的初步研究表明，在[99mtc] trodat -1结合[99mtc] trodat -1与the trodat -1与DAT位点结合的[99mtc] trodat -1结合。 我们建议进行一项初步研究，以检查MDE中的纹状体DAT水平是否代表了抑郁症的推定状态依赖性生物标志物。 对于特定目标＃1，我们会问：MDE中的纹状体DA t水平增加代表了一种依赖状态的生物标志物，成功抗抑郁治疗后会降低？ 我们假设在成功抗抑郁治疗期间，MDE患者的纹状体DAT水平增加将降低，并且对不反应治疗的患者不会明显降低。 对于特定的目标＃2，我们会问：在不抑郁的，健康的对照中，纹状体DAT级别是否会随着时间的流逝保持稳定？ 为了回答这些问题，我们将使用[99MTC] Trodat-1 Spect和MRI共定位，在44名药物毒药MDE患者中与S-妥优氨酰或安慰剂进行8周治疗之前和之后测量纹状体DAT级别。 我们将将这些结果与22个未抑郁的，健康的受试者的纹状体DAT水平进行比较，在相似条件下与[99mtc] Trodat-1 Spect在相似的条件下研究了两个单独的场合，相距8周。