Moreau X, Azorin J M, Lejeune P J, Jeanningros R
Unité 501-INSERM, Faculté de Médecine, Marseille, France.
Prog Neuropsychopharmacol Biol Psychiatry. 2000 Jan;24(1):23-35. doi: 10.1016/s0278-5846(99)00087-1.
The evolution of kinetic parameters (Vmax, maximal velocity, and Km, Michaelis constant) of red blood cell (RBC) triiodothyronine (L-T3) initial uptake was followed in 19 inpatients suffering from unipolar depression after 1 week (D7) and 4 weeks (D28) of a chronic administration of fluvoxamine, in relation with the clinical efficacy of the drug. In a drug-free state (DO), Vmax (in pmol/min/10(8) cells) and Km (in nM) were significantly increased in depressed patients (Vmax +/- S.D.= 1.02 +/- 0.29, p< 0.01 and Km +/- S.D.= 68.8 +/-15.4, p< 0.05; n=19) compared to healthy volunteers matched for age and sex (Vmax +/- S.D.= 0.82 +/- 0.15 and Km S.D.= 58.8 +/- 9.0; n= 19). When patients were dichotomized on the basis of their treatment response, responders had kinetic parameters significantly increased (Vmax +/-S.D.= 1.03 +/- 0.26, p< 0.01 and Km +/- S.D.= 71.7 +/- 18.7, p< 0.05, n= 10) compared to controls, whereas non-responders had not (Vmax +/- S.D.= 1.00 +/- 0.33, NS and Km +/- S.D.= 65.7 +/- 10.9, NS, n= 9). At D7, Vmax differed from the one of controls only in the responders (Vmax +/- S.D.= 1.03 +/-0.26, p< 0.01). In addition, the percentage of variation of the individual Vmax values during the first week of treatment was significantly lower in responders than in non-responders (deltaVmax(D7-D0) +/- S.D. in % = 10.7 +/- 6.0 and 22.0 +/- 11. 1, p< 0.05, respectively). At D28, kinetics of L-T3 uptake normalized only in the responders (Vmax +/- S.D.= 0.91 +/- 0.13, NS; Km+/-S.D.= 65.7 +/- 7.4, NS). The results indicate that both RBC L-T3 uptake at the pretreatment level and its change during the first week of fluvoxamine treatment were related to the further clinical response to the antidepressant. RBC L-T3 uptake seems to be a biological correlate of the depressive symptomatology since the disturbances disappear only with the clinical remission.
对19例单相抑郁症住院患者在长期服用氟伏沙明1周（D7）和4周（D28）后，跟踪观察红细胞（RBC）三碘甲状腺原氨酸（L-T3）初始摄取的动力学参数（Vmax，最大速度；以及Km，米氏常数）的变化，并将其与药物的临床疗效相关联。在无药状态（D0）下，与年龄和性别匹配的健康志愿者相比，抑郁症患者的Vmax（单位：pmol/分钟/10⁸个细胞）和Km（单位：nM）显著升高（抑郁症患者：Vmax±标准差 = 1.02±0.29，p < 0.01；Km±标准差 = 68.8±15.4，p < 0.05；n = 19；健康志愿者：Vmax±标准差 = 0.82±0.15，Km标准差 = 58.8±9.0；n = 19）。当根据治疗反应将患者分为两组时，与对照组相比，有反应者的动力学参数显著升高（Vmax±标准差 = 1.03±0.26，p < 0.01；Km±标准差 = 71.7±18.7，p < 0.05，n = 10），而无反应者则没有（Vmax±标准差 = 1.00±0.33，无统计学意义；Km±标准差 = 65.7±10.9，无统计学意义，n = 9）。在D7时，只有有反应者的Vmax与对照组不同（Vmax±标准差 = 1.03±0.26，p < 0.01）。此外，治疗第一周期间个体Vmax值的变化百分比在有反应者中显著低于无反应者（D7 - D0时Vmax的变化百分比±标准差分别为10.7±6.0和22.0±11.1，p < 0.05）。在D28时，只有有反应者的L-T3摄取动力学恢复正常（Vmax±标准差 = 0.91±0.13，无统计学意义；Km±标准差 = 65.7±7.4，无统计学意义）。结果表明，治疗前红细胞L-T3摄取水平及其在氟伏沙明治疗第一周期间的变化均与对抗抑郁药的进一步临床反应相关。红细胞L-T3摄取似乎是抑郁症状的生物学关联指标，因为只有在临床缓解时这些紊乱才会消失。
