Effect of Psychotherapy on Brain Serotonin Activity

心理治疗对大脑血清素活性的影响

• 批准号: 7545908
• 负责人: JAY D AMSTERDAM
• 金额: $ 21.26万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-12-26 至 2010-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7545908
• 关键词: Affect; Aftercare; Age; Antidepressive Agents; Applications Grants; Binding; Biological Markers; Brain; Brain imaging; Brain region; Clinical; Controlled Study; Data; Feasibility Studies; Functional disorder; Future; Health; Individual; Magnetic Resonance Imaging; Measures; Mental Health; Midbrain structure; Moods; Pathogenesis; Patients; Pharmaceutical Preparations; Play; Positron-Emission Tomography; Psychotherapy; Radiopharmaceuticals; Risk Behaviors; Role; Safety; Serotonin; Site; Study Subject; Time; Work; cognitive behavior therapy; density; depressed; improved; neurotransmission; novel strategies; radioligand; response; serotonin receptor; serotonin transporter; single episode major depressive disorder; single photon emission computed tomography; tool

DESCRIPTION (provided by applicant): Alterations in serotonin (5-HT) receptor and transporter (SERT) activity may play a key role in the pathogenesis and treatment of major depressive episode (MDE). SERT sites are strategically located in brain regions that may play a role in modulating mood and affect. Recent brain imaging studies suggest that altered central 5-HT activity in MDE may be reflected in reduced midbrain SERT levels, and that this disturbance may "normalize" with clinical improvement. We have recently shown a significant reduction in midbrain SERT levels in MDE patients vs. healthy controls (p<0.01) using 123I ADAM SPECT imaging. This grant proposal seeks to: (i) confirm our initial findings of reduced midbrain SERT levels in MDE patients vs. healthy controls; and, (ii) to determine if reduced midbrain SERT levels represent a state-dependent biomarker of MDE that "normalizes" with response to antidepressant therapy. We propose using 123I ADAM SPECT and MRI co-registration to measure midbrain SERT activity in MDE patients before and after treatment with cognitive behavior therapy (CBT), and compare these results with SERT levels in healthy controls studied on two separate occasions. For specific aim #1 we will ask: Do reduced midbrain SERT levels represent a bio-marker of MDE compared to non-depressed, healthy controls? For specific aim #2 we will ask: Do reduced midbrain SERT levels represent a state-dependent biomarker of MDE that "normalizes" in MDE patients who respond to CBT vs. patients who do not respond to CBT? We will also ask: Do midbrain SERT levels remain stable over time in healthy control subjects studied on two separate occasions? To answer question #1, we will measure midbrain SERT levels using 123I ADAM SPECT and MRI co-registration in drug naive MDE patients and in healthy controls. This will represent confirmatory data of our preliminary observations with 123I ADAM SPECT. We hypothesize that SERT levels will be reduced in MDE patients vs. healthy controls. To answer question #2, we will measure SERT levels in drug naive MDE patients before and after 12 weeks of CBT, and we will also measure SERT levels in healthy controls on two separate occasions 12 weeks apart. We hypothesize that reduced SERT levels in MDE patients will increase after response to CBT, and will not appreciably change in patients who do not respond to CBT. We further hypothesize that midbrain SERT levels will remain stable over time in non-depressed, healthy control subjects.

描述（由申请人提供）：5-羟色胺（5-HT）受体和转运蛋白（SERT）活性的改变可能在主要抑郁发作（MDE）的发病机理和治疗中起关键作用。 Sert站点在策略上位于大脑区域，可能在调节情绪和影响方面发挥作用。最近的大脑成像研究表明，MDE中的中央5-HT活性改变可能会反映在降低的中脑SERT水平中，并且这种干扰可能会随着临床改善而“正常化”。最近，我们使用123i Adam Spect Imaging显示了MDE患者与健康对照组（P <0.01）的中脑SERT水平的显着降低。该赠款提案试图：（i）确认我们对MDE患者中脑中脑静脉水平降低与健康对照的最初发现； （ii）确定降低的中脑Sert水平是否代表了MDE的状态依赖性生物标志物，该标志物对抗抑郁治疗的反应“正常”。我们建议使用123I ADAM SPECT和MRI共同注册，以测量使用认知行为疗法（CBT）治疗前和治疗后MDE患者中的中脑SERT活性，并将这些结果与SERT水平进行比较，在两次分别研究的健康对照中。对于特定的目标＃1，我们会问：与未抑郁的健康对照相比，中脑SERT水平降低代表MDE的生物标志物？对于特定目标＃2，我们会问：降低的中脑SERT水平是否代表了MDE的状态依赖性生物标志物，在对CBT对CBT对CBT反应的患者的MDE患者中，MDE“正常化”？我们还会问：在两次研究的健康对照对象中，中脑塞特水平是否随着时间的流逝保持稳定？为了回答问题1，我们将使用123i ADAM SPECT和MRI共同注册在药物幼稚的MDE患者和健康对照组中测量中脑Sert水平。这将代表我们使用123i Adam Spect的初步观察的确认数据。我们假设在MDE患者与健康对照组中，SERT水平将降低。为了回答问题2，我们将在CBT 12周之前和之后测量药物天真的MDE患者的SERT水平，我们还将在相隔12周的两个单独的情况下测量健康对照中的SERT水平。我们假设MDE患者的SERT水平降低将在对CBT响应后增加，并且对不反应CBT的患者不会明显改变。我们进一步假设，在不抑郁的健康对照受试者中，中脑SERT水平将随着时间的流逝而保持稳定。