Baptista Trino, Dávila Adriana, El Fakih Yamily, Uzcátegui Euderruh, Rangel Nairy N, Olivares Yamile, Galeazzi Tatiana, Vargas Doritza, Peña Rocio, Marquina David, Villarroel Vanesa, Teneud Luis, Beaulieu Serge
Departments of Physiology, Los Andes University Medical School, Mérida, Venezuela.
Int Clin Psychopharmacol. 2007 Jul;22(4):205-11. doi: 10.1097/YIC.0b013e328080ca44.
Melkersson proposed leptin dysregulation as a factor in the olanzapine-induced metabolic dysfunction. Their suggestion was based on the absence of the expected positive correlation between serum leptin levels and the BMI, and the loss of the sex-dependent difference in leptin levels, which are higher in women. Although subsequent studies did not confirm that proposal, few of them assessed basal leptin levels and corrected for body fat percentage. Along with these variables, we added a precise definition of participants out of the expected positive correlation in a large sample of schizophrenia patients. Sixty patients (26 women and 34 men) with severe schizophrenia undergoing chronic hospitalization and conventional antipsychotic treatment were switched to olanzapine (10-20 mg/day). We assessed at baseline, and at weeks 8 and 16 of treatment, the percentage of participants with abnormal correlation (out of the 95% confidence interval in the regression line) between leptin levels and the BMI, and the correlation between leptin and insulin, glucose, the insulin resistance index, c-reactive protein (CRP) and treatment response. Leptin levels were higher in women than in men (P<0.01). The positive correlation between leptin levels, BMI and percentage of fat were preserved. After olanzapine, 3.8% of women and 2.9-5.8% of men were out the 95% confidence interval, and the proportion was similar at baseline. Glucose, insulin, the insulin resistance index and the CRP levels significantly increased after olanzapine. The impact of olanzapine on leptin regulation appears discrete and limited to a small number of participants. Additional studies must clarify the features that render them to metabolic dysregulation.
梅尔克斯森提出瘦素调节异常是奥氮平所致代谢功能障碍的一个因素。他们的这一观点基于血清瘦素水平与体重指数（BMI）之间缺乏预期的正相关，以及瘦素水平的性别差异消失（女性瘦素水平更高）。尽管后续研究并未证实这一观点，但很少有研究评估基础瘦素水平并校正体脂百分比。除了这些变量，我们在一大群精神分裂症患者样本中，对出现预期正相关之外的参与者进行了精确界定。60例患有重度精神分裂症且正在接受慢性住院治疗及传统抗精神病药物治疗的患者（26名女性和34名男性）换用奥氮平（10 - 20毫克/天）。我们在基线时以及治疗的第8周和第16周，评估了瘦素水平与BMI之间相关性异常（超出回归线95%置信区间）的参与者百分比，以及瘦素与胰岛素、葡萄糖、胰岛素抵抗指数、C反应蛋白（CRP）和治疗反应之间的相关性。女性的瘦素水平高于男性（P<0.01）。瘦素水平、BMI和脂肪百分比之间的正相关得以保留。使用奥氮平后，3.8%的女性和2.9 - 5.8%的男性超出了95%置信区间，且该比例在基线时相似。使用奥氮平后，葡萄糖、胰岛素、胰岛素抵抗指数和CRP水平显著升高。奥氮平对瘦素调节的影响似乎是离散的，且仅限于少数参与者。更多研究必须阐明导致他们出现代谢功能障碍的特征。
