Effect of Psychotherapy on Brain Serotonin Activity

描述(申请人提供)：5-羟色胺(5-羟色胺)受体和转运体(SERT)活性的改变可能在严重抑郁发作(MDE)的发病机制和治疗中发挥关键作用。SERT位置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，MDE中枢5-羟色胺活性的改变可能反映在中脑SERT水平的降低上，随着临床的改善，这种紊乱可能会“正常化”。我们最近使用~(123)I ADAM SPECT显像显示，与健康对照组(P&lt；0.01)相比，MDE患者的中脑SERT水平显著降低。这项拨款提案旨在：(I)证实我们最初发现的MDE患者与健康对照组相比中脑SERT水平降低；以及(Ii)确定中脑SERT水平降低是否代表MDE的一个状态依赖的生物标记物，该标记物在抗抑郁药物治疗后“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治疗(CBT)治疗前后的中脑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的SERT水平进行比较。对于特定的目标1，我们将问：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，我们将问：降低的中脑SERT水平是否代表MDE的状态依赖的生物标记物，与CBT无效的MDE患者相比，MDE患者对CBT有反应的MDE患者“正常化”？我们还会问：在两个不同的场合研究的健康对照组受试者中，中脑SERT水平是否随着时间的推移保持稳定？为了回答第一个问题，我们将使用123I ADAM SPECT和MRI联合注册来测量药物初学者MDE患者和健康对照组的中脑SERT水平。这将代表我们用~(123)I ADAM SPECT初步观察到的确证数据。我们假设与健康对照组相比，MDE患者的SERT水平将降低。为了回答问题2，我们将在CBT治疗12周之前和12周后测量药物初学者MDE患者的SERT水平，我们还将在相隔12周的两个不同场合测量健康对照组的SERT水平。我们假设MDE患者降低的SERT水平在CBT治疗有效后会增加，而在CBT无效的患者中不会有明显的变化。我们进一步假设，在非抑郁的健康对照受试者中，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.