Malison R T, Price L H, Berman R, van Dyck C H, Pelton G H, Carpenter L, Sanacora G, Owens M J, Nemeroff C B, Rajeevan N, Baldwin R M, Seibyl J P, Innis R B, Charney D S
Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Biol Psychiatry. 1998 Dec 1;44(11):1090-8. doi: 10.1016/s0006-3223(98)00272-8.
Prior research has suggested reductions in the density of serotonin transporter (SERT) binding sites in blood platelets and post-mortem brain tissue of depressed patients. We sought to determine whether patients with unipolar major depression have diminished SERT availability as assessed by both brainstem [123I] beta-CIT SPECT and platelet [3H]paroxetine binding.
Drug-free depressed and healthy subjects were injected with 211 +/- 22 MBq [123I] beta-CIT and imaged 24 +/- 2 h later under equilibrium conditions. A ratio of specific to nonspecific brain uptake (V3" = (brainstem-occipital)/occipital), a measure proportional to the binding potential (Bmax/Kd), was used for all comparisons.
Results showed a statistically significant reduction in brainstem V3" values in depressed as compared to healthy subjects (3.1 +/- .9 vs. 3.8 +/- .8, p = .02). Platelet [3H]paroxetine binding was not altered (Bmax = 2389 +/- 484 vs. 2415 +/- 538 fmol/mg protein, p = .91) and was not significantly correlated with brainstem [123I] beta-CIT binding (r = -0.14, p = .48).
These data are the first to suggest reductions in the density of brain SERT binding sites in living depressed patients. These findings provide further support for a preeminent role for alterations in serotonergic neurons in the pathophysiology of depression.
先前的研究表明，抑郁症患者血小板和死后脑组织中5-羟色胺转运体（SERT）结合位点的密度降低。我们试图确定单相重度抑郁症患者经脑干[123I]β-CIT单光子发射计算机断层扫描（SPECT）和血小板[3H]帕罗西汀结合评估的SERT可用性是否降低。
对未服用药物的抑郁症患者和健康受试者注射211±22兆贝可[123I]β-CIT，并在24±2小时后在平衡条件下进行成像。所有比较均使用特异性与非特异性脑摄取的比值（V3” =（脑干-枕叶）/枕叶），该比值与结合潜力（Bmax/Kd）成正比。
结果显示，与健康受试者相比，抑郁症患者脑干V3”值在统计学上显著降低（3.1±0.9对3.8±0.8，p = 0.02）。血小板[3H]帕罗西汀结合未改变（Bmax = 2389±484对2415±538飞摩尔/毫克蛋白质，p = 0.91），且与脑干[123I]β-CIT结合无显著相关性（r = -0.14，p = 0.48）。
这些数据首次表明，活着的抑郁症患者脑SERT结合位点密度降低。这些发现为5-羟色胺能神经元改变在抑郁症病理生理学中的突出作用提供了进一步支持。
