Effect of Psychotherapy on Brain Serotonin Activity

描述（由申请人提供）：5-羟色胺（5-HT）受体和转运体（SERT）活性的改变可能在重度抑郁发作（MDE）的发病机制和治疗中起关键作用。SERT位点战略性地位于大脑区域，可能在调节情绪和情感方面发挥作用。最近的脑成像研究表明，改变中央5-羟色胺活动在MDE可能反映在减少中脑SERT水平，这种干扰可能会“正常化”与临床改善。我们最近使用123 I ADAM SPECT成像显示，与健康对照组相比，MDE患者中脑SERT水平显著降低（p<0.01）。这项拨款建议旨在：（i）证实我们的最初发现，即MDE患者与健康对照相比中脑SERT水平降低;和（ii）确定降低的中脑SERT水平是否代表MDE的状态依赖性生物标志物，其随着抗抑郁治疗的响应而“正常化”。我们建议使用123 I ADAM SPECT和MRI共配准来测量认知行为疗法（CBT）治疗前后MDE患者的中脑SERT活性，并将这些结果与在两个不同场合研究的健康对照组中的SERT水平进行比较。对于具体的目标#1，我们会问：与非抑郁的健康对照相比，中脑SERT水平降低是否代表MDE的生物标志物？对于具体目标#2，我们会问：降低中脑SERT水平是否代表MDE的状态依赖性生物标志物，其在对CBT有反应的MDE患者与对CBT无反应的患者中“正常化”？我们还将问：在两个不同的场合研究的健康对照受试者中，中脑SERT水平是否随着时间的推移保持稳定？为了回答问题#1，我们将使用123 I ADAM SPECT和MRI共配准来测量未经药物治疗的MDE患者和健康对照中的中脑SERT水平。这将代表我们用123 I ADAM SPECT初步观察的确认数据。我们假设SERT水平在MDE患者与健康对照组相比会降低。为了回答问题#2，我们将在12周CBT之前和之后测量未经药物治疗的MDE患者的SERT水平，并且我们还将在间隔12周的两个不同场合测量健康对照的SERT水平。我们假设MDE患者中SERT水平的降低在对CBT做出反应后会增加，并且在对CBT没有反应的患者中不会发生明显变化。我们进一步假设，中脑SERT水平将保持稳定，随着时间的推移，在非抑郁症，健康的对照组。

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.