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双相情感障碍、重性抑郁障碍和精神分裂症患者前扣带回皮质 5-HT 受体的分布和水平 - 一项放射自显影研究。

Distribution and levels of 5-HT receptors in anterior cingulate cortex of patients with bipolar disorder, major depressive disorder and schizophrenia - An autoradiography study.

机构信息

Center for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden.

Center for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden.

出版信息

Eur Neuropsychopharmacol. 2017 May;27(5):504-514. doi: 10.1016/j.euroneuro.2017.02.011. Epub 2017 Mar 18.

Abstract

The serotonin 1B receptor has recently received more interest as a possible new target for pharmacological treatment of psychiatric disorders. However, the exact mechanisms of action remain unclear. This study aimed to examine the binding distribution and levels of the serotonin 1B receptor in-depth in the anterior cingulate cortex (ACC) and provide more insight in its functional role in bipolar disorder (BD), major depressive disorder (MDD) and schizophrenia (SZ). Serotonin 1B receptor binding distribution was visualized with high resolution autoradiography (ARG), using the radioligand [H]AZ10419369, in postmortem ACC tissue from patients diagnosed with BD (n=14), MDD (n=12), SZ (n=13) and healthy subjects (n=13). Moreover, a quantification of receptor binding was made with ARG, in relation to patient group, age and gender. In all subject groups a significantly higher specific binding of serotonin 1B receptor was measured in the outer ACC layers compared to the inner ACC layers. Correlation analysis with ARG binding patterns of several radioligands resulted in a significant correlation with glutamatergic N-methyl-D-aspartate receptor binding in the outer layers. No significant difference was found between subject groups in binding levels and distribution. In female subjects a significantly lower receptor binding was found than in male subjects, which was most profound in patients diagnosed with MDD. The binding distribution of the serotonin 1B receptor found in this study supports a role in glutamate transmission in the ACC and was not shown to be significantly altered in BD, MDD or SZ. A gender difference in serotonin 1B receptor binding was found.

摘要

5-羟色胺 1B 受体最近作为治疗精神疾病的药理学新靶点引起了更多关注。然而,其确切的作用机制仍不清楚。本研究旨在深入研究前扣带皮层(ACC)中 5-羟色胺 1B 受体的结合分布和水平,并进一步了解其在双相情感障碍(BD)、重度抑郁症(MDD)和精神分裂症(SZ)中的功能作用。使用放射性配体 [H]AZ10419369,通过高分辨率放射自显影(ARG),对诊断为 BD(n=14)、MDD(n=12)、SZ(n=13)和健康受试者(n=13)的死后 ACC 组织中的 5-羟色胺 1B 受体结合分布进行了可视化。此外,还通过 ARG 对受体结合进行了定量分析,与患者组、年龄和性别有关。在所有受试者组中,与内 ACC 层相比,外 ACC 层中 5-羟色胺 1B 受体的特异性结合明显更高。与外皮层谷氨酸能 N-甲基-D-天冬氨酸受体结合的 ARG 结合模式的相关分析显示出显著相关性。在结合水平和分布方面,各组之间未发现显著差异。在女性受试者中,受体结合明显低于男性受试者,在被诊断为 MDD 的患者中最为明显。本研究中发现的 5-羟色胺 1B 受体结合分布支持在 ACC 中谷氨酸传递的作用,并且在 BD、MDD 或 SZ 中未显示出明显改变。发现 5-羟色胺 1B 受体结合存在性别差异。

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