Hrdina P D, Bakish D, Ravindran A, Chudzik J, Cavazzoni P, Lapierre Y D
Department of Psychiatry, University of Ottawa, Ontario, Canada.
Psychiatry Res. 1997 Feb 7;66(2-3):73-85. doi: 10.1016/s0165-1781(96)03046-6.
This study examined, in the largest sample of major depressives reported so far, platelet serotonergic parameters (5-HT uptake, [3H]paroxetine binding and 5-HT2A receptors measured by [3H]LSD binding) in 60 antidepressant-free depressed patients and 40 age- and gender-matched control subjects before treatment, and in 45 major depression patients during treatment with antidepressants. We found that, at baseline, the density (Bmax) of 5-HT2A receptors was significantly higher (by 39%) in depressed patients than in controls. Suicidal patients had significantly higher Bmax values than controls or non-suicidal patients. The rate of serotonin uptake (Vmax), but not the uptake at a single concentration, was significantly higher in depressed patients, particularly in females. There was no significant difference between the Kd or Bmax of [3H]paroxetine binding in control and depressed subjects. Treatment with antidepressant drugs of different pharmacological profile had no significant effect on the density of 5-HT2A receptors, nor did the receptor number predict the response to treatment. The affinity of serotonin uptake site for 5-HT and [3H]paroxetine significantly decreased during treatment with antidepressants, particularly SSRIs. Suppression of 5-HT uptake correlated with decreases in Hamilton depression (HAMD) scores. Our data suggest that the increased density of platelet 5-HT2A receptors may be associated with untreated major depression in antidepressant-free depressed patients, in particular those with suicidal thoughts. The persistence after antidepressant treatment and clinical improvement would suggest that up-regulation of 5-HT2A receptors is a trait rather than state phenomenon. Correlation of 5-HT uptake suppression with decreases in HAMD scores suggests that serotonin uptake inhibition is a relevant factor in antidepressant drug effect and clinical improvement.
本研究在目前所报道的最大样本的重度抑郁症患者中，检测了60例未服用抗抑郁药的抑郁症患者和40例年龄及性别匹配的对照者治疗前的血小板血清素能参数（5-羟色胺摄取、[3H]帕罗西汀结合以及通过[3H]麦角酸二乙酰胺结合测量的5-HT2A受体），以及45例服用抗抑郁药治疗期间的重度抑郁症患者的这些参数。我们发现，在基线时，抑郁症患者5-HT2A受体的密度（Bmax）显著高于对照组（高39%）。有自杀倾向的患者的Bmax值显著高于对照组或无自杀倾向的患者。抑郁症患者，尤其是女性，血清素摄取率（Vmax）显著更高，但单一浓度下的摄取量无显著差异。对照组和抑郁症患者之间[3H]帕罗西汀结合的解离常数（Kd）或Bmax无显著差异。不同药理特性的抗抑郁药治疗对5-HT2A受体的密度无显著影响，受体数量也不能预测治疗反应。在使用抗抑郁药治疗期间，尤其是使用选择性5-羟色胺再摄取抑制剂（SSRI）时，血清素摄取位点对5-羟色胺和[3H]帕罗西汀的亲和力显著降低。5-羟色胺摄取的抑制与汉密尔顿抑郁量表（HAMD）评分的降低相关。我们的数据表明，血小板5-HT2A受体密度增加可能与未服用抗抑郁药的抑郁症患者的未治疗的重度抑郁症有关，尤其是那些有自杀念头的患者。抗抑郁药治疗和临床改善后该现象持续存在，这表明5-HT2A受体上调是一种特质而非状态现象。5-羟色胺摄取抑制与HAMD评分降低之间的相关性表明，血清素摄取抑制是抗抑郁药作用和临床改善的一个相关因素。
