Effect of Psychotherapy on Brain Serotonin Activity

描述（由申请人提供）：血清素（5-HT）受体和转运体（SERT）活性的改变可能在重度抑郁发作（MDE）的发病和治疗中起关键作用。SERT位点战略性地位于可能在调节情绪和情感方面发挥作用的大脑区域。最近的脑成像研究表明，MDE中脑5-羟色胺活性的改变可能反映在中脑SERT水平的降低上，并且这种干扰可能随着临床改善而“正常化”。我们最近使用123I ADAM SPECT成像显示，与健康对照相比，MDE患者中脑SERT水平显著降低（p<0.01）。本拨款提案旨在：(i)证实我们的初步发现，MDE患者中脑SERT水平与健康对照组相比降低；（ii）确定中脑SERT水平降低是否代表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“正常化”。我们建议使用123I ADAM SPECT和MRI联合注册来测量MDE患者在接受认知行为疗法（CBT）治疗前后的中脑SERT活性，并将这些结果与在两个不同情况下研究的健康对照组的SERT水平进行比较。对于具体目标#1，我们会问：与非抑郁的健康对照组相比，中脑SERT水平降低是否代表MDE的生物标志物？对于特定的目标#2，我们会问：中脑SERT水平的降低是否代表了对CBT有反应的MDE患者与对CBT无反应的MDE患者之间“正常化”的MDE状态依赖的生物标志物？我们还会问：在两种不同的情况下，健康对照受试者的中脑SERT水平是否随时间保持稳定？为了回答问题1，我们将在未用药的MDE患者和健康对照中使用123I ADAM SPECT和MRI联合登记来测量中脑SERT水平。这将代表我们用123I ADAM SPECT初步观察的验证数据。我们假设与健康对照相比，MDE患者的SERT水平会降低。为了回答问题2，我们将测量未用药MDE患者在CBT治疗12周前后的SERT水平，我们也将在相隔12周的两个不同情况下测量健康对照的SERT水平。我们假设MDE患者降低的SERT水平在对CBT有反应后会增加，而对CBT无反应的患者不会有明显变化。我们进一步假设，在非抑郁、健康的对照组中，中脑SERT水平将随着时间的推移保持稳定。

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.