Decreased brain serotonin 5-HT1A receptor availability in medication-naive patients with major depressive disorder: an in-vivo imaging study using PET and [carbonyl-11C]WAY-100635
Decreased brain serotonin 5-HT1A receptor availability in medication-naive patients with major depressive disorder: an in-vivo imaging study using PET and [carbonyl-11C]WAY-100635
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DOI：
10.1017/s1461145707008140
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发表时间：
2008-06-01
影响因子：
4.8
通讯作者：
Hietala, Jarmo
中科院分区：
文献类型：
--
作者：
Hirvonen, Jussi;Karlsson, Hasse;Hietala, Jarmo
5-羟色胺（5-HT）参与了重度抑郁症（MDD）的病理生理过程。在众多的肾上腺素能受体中，5-HT 1A受体亚型由于其参与认知、海马神经发生和抗抑郁药物的作用机制而受到关注。先前的影像学研究表明，MDD患者5-HT A受体的可用性改变，但既往抗抑郁药物治疗和疾病的慢性化可能会混淆解释。我们使用正电子发射断层扫描（PET）成像与[羰基-C-11]WAY-100635（5-HT 1A受体的放射性配体）检查了21例药物初治的MDD患者，沿着15例健康对照受试者。与受体的结合在区域和体素水平上进行评估，结合电位（BP）使用动脉血输入进行估计。与健康对照组相比，[羰基-C-11]WAY-100635在MDD患者的大部分脑区降低了BP，范围为-9%至-25%。体素水平分析通过显示[羰基-C-11]WAY-100635 BP的广泛还原证实了这一发现。血压与HAMD总分之间没有统计学显著相关性，但较低的血压与失眠的可能性较高相关。这项研究表明，在一个相对较大的样本的药物初治的初级保健MDD患者中，5-羟色胺5-HT 1A受体的可用性普遍降低，表明这种受体亚型参与疾病的病理生理学。缺乏与疾病的整体严重程度的相关性可能与抑郁症中这种异常的主要特征样性质有关。
Serotonin (5-HT) is involved in the pathophysiology of major depressive disorder (MDD). Among the numerous serotonergic receptors, the 5-HT1A receptor subtype is of interest because of its involvement in cognition, hippocampal neurogenesis, and mechanism of action of antidepressant drugs. Previous imaging studies have Suggested altered availability of 5-HT A receptors in MDD but prior antidepressant medication and chronicity of the illness may confound the interpretation. We examined 21 drug-naive primary-care patients with MDD using positron emission tomography (PET) imaging with [carbonyl-C-11]WAY-100635, a radioligand for 5-HT1A receptors, along with 15 healthy control subjects. Binding to receptors was, assessed both regionally and at voxel level with the binding potential (BP) that was estimated using arterial blood input. Compared with healthy controls, the BP of [carbonyl-C-11]WAY-100635 was reduced in patients with MDD in most brain regions, ranging from -9% to -25%. Voxel-level analysis confirmed this finding by showing a widespread reduction of [carbonyl-C-11]WAY-100635 BP. No statistically significant associations were observed between BP and total HAMD scores in the patients, but lower BP was associated with higher likelihood of insomnia. This study demonstrated a widespread reduction in the availability of serotonin 5-HT1A receptors in a relatively large sample of drug-naive primary-care patients with MDD, suggesting the involvement of this receptor subtype in the pathophysiology of the illness. Lack of correlation with overall severity of the illness may relate to a largely trait-like nature of this abnormality in depressive disorders.