Brunswick David J, Amsterdam Jay D, Mozley P David, Newberg Andrew
Depression Research Unit, Department of Radiology, University of Pennsylvania Medical Center, Philadelphia, PA 19104, USA.
Am J Psychiatry. 2003 Oct;160(10):1836-41. doi: 10.1176/appi.ajp.160.10.1836.
Studies of laboratory animals have shown that administration of antidepressants of all pharmacological classes produces changes in dopamine transporter binding affinity. These observations suggest that dopamine transporter function may play a critical role in the pathophysiology of depression. The present study was an examination of the availability of brain dopamine transporter sites in patients with major depression and in healthy comparison subjects.
Single photon emission computed tomographic (SPECT) brain scans were acquired for 15 drug-free depressed patients and 46 age- and gender-matched healthy comparison subjects by using [(99m)Tc]TRODAT-1, a selective dopamine transporter imaging agent. Specific regions of interest in the basal ganglia and supratentorial areas of the brain were examined. Specific uptake values of dopamine transporter [(99m)Tc]TRODAT-1 binding affinity were calculated from the SPECT scan data, and the values for the patients and healthy subjects were compared.
The specific uptake values of [(99m)Tc]TRODAT-1 binding were significantly higher in the right anterior putamen (23%), right posterior putamen (36%), left posterior putamen (18%), and left caudate nucleus (12%) of the patients than in the comparison subjects. These differences persisted when the data were further analyzed according to gender and age.
Dopamine transporter affinity may be higher than normal in the basal ganglia of depressed patients. These findings suggest that dopamine function may be altered in depression and may also be a mechanism of antidepressant activity.
对实验动物的研究表明,给予所有药理学类别的抗抑郁药都会使多巴胺转运体结合亲和力发生变化。这些观察结果表明,多巴胺转运体功能可能在抑郁症的病理生理学中起关键作用。本研究旨在检测重度抑郁症患者和健康对照者脑内多巴胺转运体位点的可用性。
使用选择性多巴胺转运体显像剂[(99m)Tc]TRODAT-1,对15名未服用药物的抑郁症患者和46名年龄及性别匹配的健康对照者进行单光子发射计算机断层扫描(SPECT)脑成像。检查大脑基底神经节和幕上区域的特定感兴趣区。根据SPECT扫描数据计算多巴胺转运体[(99m)Tc]TRODAT-1结合亲和力的特定摄取值,并比较患者和健康受试者的值。
患者右侧前壳核(23%)、右侧后壳核(36%)、左侧后壳核(18%)和左侧尾状核(12%)的[(99m)Tc]TRODAT-1结合特异性摄取值显著高于对照受试者。根据性别和年龄进一步分析数据时,这些差异仍然存在。
抑郁症患者基底神经节中的多巴胺转运体亲和力可能高于正常水平。这些发现表明,抑郁症中多巴胺功能可能发生改变,这也可能是抗抑郁活性的一种机制。