Similar frequency of abnormal correlation between serum leptin levels and BMI before and after olanzapine treatment in schizophrenia

Abstract

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.

C-reactive protein is increased in schizophrenia but is not altered by antipsychotics: meta-analysis and implications

“…One of the most common explanations of the inflammatory hypothesis of SZ presumes that the inflammatory changes found in this disorder are attributable to and are merely a marker of the metabolic syndrome and the unhealthy lifestyle that commonly accompanies severe psychiatric conditions. 22,40 Our analyses uncover that CRP levels are moderately increased in subjects with SZ within 1 year of the occurrence of the first episode of psychosis and remains moderately increased with progression of SZ. In order to further clarify this point, we conducted a series of analyses of sub-groups and verified that CRP levels are increased in SZ in comparison with controls even when only studies paired by BMI and age were considered, and also when only studies that included subjects free of any clinical condition besides SZ were examined.…”

“…17,18,21,24,25,29,30,[33][34][35]41 Four studies were population studies 14,18,30,34 and the other 15 were case-control studies conducted in in-patient or out-patient units. 17,[19][20][21][22][23][24][25][26][27][28][29][31][32][33][35][36][37][38][39][40][41] Five studies provided data on subjects with first episode psychosis 19,27,31,34,38 and 14 studies provided data on subjects with chronic SZ 14,17,18,21,24,25,[28][29][30]…”

“…Twenty-six studies fulfiled our inclusion criteria, 19 for the between-group meta-analysis of SZ versus control, 14,[17][18][19]21,24,25,[27][28][29][30][31][33][34][35][36]38,39,41 6 for the withingroup meta-analysis of CRP changes after initiation of antipsychotics 20,21,23,27,32,37 and 3 for the within-group metaanalysis of CRP changes with substitution of the type of the antipsychotic. 22,26,40 Some studies provided more than one pairwise comparison, as whenever possible we extracted data according to medication status.…”

“…22,40 Once more, the body of evidence here is contradictory, with some longitudinal clinical studies showing worsening of metabolic syndrome and, ultimately, increased levels of CRP after initiation of antipsychotics, some showing no change and some showing decreased levels of CRP after initiation of these medications. [20][21][22][23]26,27,32,37,40 On the other hand, animal studies suggest that antipsychotics may decrease IL-6 and, as a theoretical consequence, negatively modulate CRP. 42,43 Inconsistent findings among the studies might be caused by heterogeneous patient populations, variations in methodology or small sample sizes lacking statistical power.…”

Alteraciones metabólicas asociadas al uso de terapia antipsicótica

“…Togo, encuentra un aumento en los niveles de esta proteína en pacientes en terapia prolongada con olanzapina y risperidona 39 , en tanto que el mismo grupo, en un estudio posterior, no encontró diferencias significativas en los niveles de adiponectina, pero sí elevación de leptina y disminución de ghrelina en pacientes expuestos a olanzapina por periodos menores a 4 semanas 40 . En relación a leptina, se ha planteado que se alteraría la relación fisiológica normal entre tejido adiposo y los niveles de circulantes 41,42 . La falta de consistencia en los resultados puede estar relacionada con la heterogeneidad clínica de esta enfermedad y las diferentes características de los pacientes seleccionados para estudio en cuanto a tiempo de evolución, uso de terapia antipsicótica y de otros fármacos asociados.…”