Antidepressant treatment reduces serotonin-1A autoreceptor binding in major depressive disorder.
Antidepressant treatment reduces serotonin-1A autoreceptor binding in major depressive disorder.
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DOI：
10.1016/j.biopsych.2012.11.012
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发表时间：
2013-07-01
影响因子：
10.6
通讯作者：
Parsey, Ramin V.
中科院分区：
文献类型：
--
作者：
Gray, Neil A.;Milak, Matthew S.;DeLorenzo, Christine;Ogden, R. Todd;Huang, Yung-yu;Mann, J. John;Parsey, Ramin V.
关键词：
慢性选择性5-羟色胺再摄取抑制剂（SSRI）给药啮齿动物脱敏或下调中缝5-HT 1A自身受体。我们以前发现抗抑郁药初治和近期未用药的重性抑郁症患者5-HT 1A结合升高，现在报告SSRI治疗对抑郁症患者5-HT 1A自身受体的影响。在使用SSRI治疗重度抑郁症（MDD）5 - 9周（平均47±8天）之前和之后，使用[11 C]-WAY-100635 PET对未用药受试者的5-HT 1A结合（BPF）进行定量。19例近期无抗抑郁药物治疗史的受试者完成了代谢物校正动脉输入功能的[11 C]WAY-100635 PET扫描，并在疗程前后评定了抑郁严重程度。SSRI治疗后，中缝中5-HT 1A自身受体BPF降低18%（df= 1.18; F=5.12; p=0.036）。然而，5-HT 1A自身受体BPF的降低程度与抑郁症的改善无关（df= 1.16; F=1.27; p=0.276）。通过SSRI治疗抑郁症下调5-HT 1A自身受体结合与动物研究一致。这可能是SSRI临床反应的必要但不充分的要求。PET激动剂配体选择性结合这种受体的高亲和力构象，可以确定SSRI是否也会引起自身受体的脱敏，如一些啮齿动物研究所报告的那样，以及这种作用是否可能与临床反应有关。
Chronic selective serotonin reuptake inhibitor (SSRI) administration to rodents desensitizes or downregulates raphe 5-HT1A autoreceptors. We previously found elevated 5-HT1A binding in antidepressant-naïve and not recently-medicated major depressive disorder, and now report the effect of SSRI treatment on 5-HT1A autoreceptors in depressed patients. 5-HT1A binding (BPF) was quantified in medication-free subjects using PET with [11C]-WAY-100635 before and after treatment of major depressive disorder (MDD) with an SSRI for 5 to 9 weeks (mean 47±8 days). 19 subjects without recent history of antidepressant pharmacotherapy completed both [11C]WAY-100635 PET scans with a metabolite-corrected arterial input function and depression severity was rated before and after the treatment course. 5-HT1A autoreceptor BPF in the raphe was reduced 18% on SSRI treatment (df=1,18; F=5.12; p=0.036). However, the degree of reduction in 5-HT1A autoreceptor BPF was unrelated to improvement in depression (df=1,16; F=1.27; p=0.276). Downregulation of 5-HT1A autoreceptor binding by SSRI treatment of major depression is consistent with animal studies. This may be a necessary but insufficient requirement for clinical response to SSRIs. A PET agonist ligand that binds selectively to the high affinity conformation of this receptor can determine whether SSRIs also cause desensitization of the autoreceptor as reported by some rodent studies, and whether that effect may be related to clinical response.
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影响因子：
10.6
作者：
Parsey, RV;Oquendo, MA;Mann, JJ
通讯作者：
Mann, JJ
DOI：
10.1097/00004647-200007000-00011
发表时间：
2000-07-01
影响因子：
6.3
作者：
Parsey, RV;Slifstein, M;Laruelle, M
通讯作者：
Laruelle, M
影响因子：
2.9
作者：
Naudon, L;El Yacoubi, M;Costentin, J
通讯作者：
Costentin, J
影响因子：
3.7
作者：
Navines, Ricard;Martin-Santos, Rocio;Gasto, Cristobal
通讯作者：
Gasto, Cristobal
影响因子：
6.3
作者：
Parsey, RV;Arango, V;Mann, JJ
通讯作者：
Mann, JJ