The investigation of leptin and hypothalamic neuropeptides role in first attack psychotic male patients: Olanzapine monotherapy (original) (raw)
Related papers
Plasma nitric oxide and leptin values in patients with olanzapine-induced weight gain
Journal of Psychiatric Research, 2007
We previously investigated leptin levels in antipsychotic-induced weight gain and found that atypical antipsychotic, especially clozapine and olanzapine-induced weight gain is related to increased levels of leptin. It has been suggested that nitric oxide (NO) is a potential regulator of leptin-induced lipolysis. To explore the pathophysiology of weight gain during atypical antipsychotic treatment, we planned to investigate olanzapine's influence on leptin and NO levels and weight gain. The study comprised 21 patients with schizophrenia who were enrolled in olanzapine monotherapy, and 21 healthy controls. The fasting plasma NO and leptin levels were measured in both patients and controls at baseline. The patients were also evaluated at sixth week according to the Positive and Negative Syndrome Scale (PANSS), body mass index (BMI), weight, serum leptin and NO levels. At baseline, the mean leptin level in the olanzapine group was not different compared to that in controls after BMI or age adjustment. A significant increase in leptin levels by means of olanzapine use was seen (P < 0.01). Higher plasma NO levels were observed in patients with schizophrenia compared with the control group at baseline (P < 0.01). At the evaluation of week 6, a significant decrease in the mean plasma NO level was found in the olanzapine group (P < 0.05). The changes in total PANSS scores were correlated with change in leptin levels (r = 0.58, P < 0.05), and with the change in weight (r = 0.54, P < 0.05). In addition, there was a severe significant negative correlation between the changes in leptin levels and NO levels (r = 0.73, P < 0.01). The results confirmed that leptin and NO might be associated with olanzapine-induced weight gain.
International Clinical Psychopharmacology, 2007
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.
International Clinical Psychopharmacology, 2010
The objective of the study was to investigate the change of body mass index (BMI), waist circumference, lipid profile, leptin, ghrelin, orexin, visfatin, agouti-related protein, and cholecystokinin levels during 6 weeks of olanzapine treatment in newly diagnosed first-episode drug naive, young adult, nonobese male patients with psychosis. Twenty male participants who were all first-episode drug naive psychotic patients without prominent affective signs and symptoms and 22 healthy male controls of similar age were included. BMI, waist circumference, fasting glucose, and lipid profiles were measured, and Positive and Negative Syndrome Scale and Brief Psychiatric Rating Scale scores were obtained at baseline, during the second and sixth week of treatment, and the aforementioned neuropeptide levels were measured at baseline and during the sixth week of treatment. Treatment was associated with significant increases in BMI, waist circumference, serum triglyceride, and low-density lipoprotein levels. BMI levels increased more than 7% in over 75% of the patients. Leptin increased, and ghrelin and orexin decreased significantly with olanzapine treatment, whereas cholecystokinin, visfatin, and agouti-related protein levels did not change significantly. In conclusion, consistent with previous studies, we found increased BMI, leptin and lipids during olanzapine treatment. Association of neuropeptide level changes with symptom improvement might be mediated by the dopaminergic and serotonergic systems. Int Clin Psychopharmacol 25:165-171
International journal of obesity (2005), 2012
Significant weight gain is a problematic side effect of treatment with the antipsychotic drug olanzapine (OLA). Previous studies in rats suggest that one of the contributing factors is an impairment in satiation that results in increased food intake. However, the mechanisms underlying this impairment in satiation remain largely unclear. In this study, we determined the effect of OLA on levels of leptin, insulin, ghrelin, cholecystokinin (CCK), glucagon-like peptide-1, peptide YY and amylin in male rats that had received a fixed amount of food. OLA did not affect the secretion of any of these hormones, except for ghrelin levels, which were increased compared with controls. Furthermore, when ghrelin levels were determined in rats just before they received their meal, OLA caused a significant increase in ghrelin levels compared with controls, whereas OLA failed to affect baseline ghrelin levels. Next, we investigated the effect of OLA on the efficacy of CCK to reduce meal size. With co...
Journal of Psychopharmacology, 2006
Many of olanzapine's (OLZ) actions in humans related to weight regulation can be modelled in female rats (Cooper et al., 2005). Such effects include weight gain, hyperphagia, enhanced visceral adiposity and elevated Levels of insulin and adiponectin. As sex differences have been reported in the effects of antipsychotic drugs, including OLZ, in rats, the current study extended our study in female rats by directly comparing the actions of OLZ in maLes using identical methodology. Individually housed male Han Wistar rats were administered OLZ twice daily (i.p.), at 0, 1, 2, and 4 mg/kg over 21 days. Both differences from, and simiLarities to, the data obtained in females were obtained. Males treated with OLZ showed reduced weight gain, enhanced visceral adiposity and reduced Lean muscle mass. There were no accompanying changes in food or water intake. OLZ did not induce changes in plasma Levels of insulin, Leptin or gLucose. Significant elevation of adiponectin was observed. OLZ-tr...
Effects of second generation antipsychotics on leptin and ghrelin
Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2008
Background: Weight gain is a major side effect of antipsychotic treatment. Some atypical antipsychotic agents have profound effects on weight. Body weight is regulated by a complex system, including both peripheral and central factors. Two of the hormones that seem to play an important role in the regulation of food intake, energy metabolism, and body weight are leptin and ghrelin. Leptin is a mediator of long-term regulation of energy balance, suppressing food intake and thereby inducing weight loss. Ghrelin on the other hand is a fast-acting hormone, seemingly playing a role in meal initiation. In this present study it is aimed to compare the effects of five different atypical antipsychotic medications on leptin and ghrelin. Method: 112 patients who were treated either with clozapine (n = 20), olanzapine (n = 28), risperidone (n = 22), quetiapine (n = 20) or amisulpride (n = 22) as monotherapy for at least one year and age, gender, and body mass index (BMI) matched control group (n = 23) were assessed cross-sectionally. Ghrelin and leptin levels were measured with enzyme-immunoassay. Results: When fasting serum leptin levels were compared between groups, control group had the highest mean value (9.2 ± 6.7) and amisulpride group had the lowest mean value (3.7 ± 2.1) but still there was no statistically significant difference between six groups (F = 1993, p = 0.084). In the comparison of the mean values of fasting serum ghrelin levels there was a statistically significant difference between groups (F = 11,473, p = 0.00). In post-hoc analysis it was seen that the control group had the lowest ghrelin level (194.5 ± 86.8). Quetiapine treated group (378.1 ± 260.4) had similar fasting serum ghrelin levels to control group. All the other antipsychotic treatment groups had significantly higher levels of fasting serum ghrelin compared to control group, highest in amisulpride treated group (597.0 ± 150.0). Conclusion: The weight-gain side effect of atypical antipsychotics can be related with the orexigenic effect of elevated serum ghrelin rather than leptin deficit. Among the five widely used atypical antipsychotics quetiapine is the only one which does not elevate the ghrelin level.
Current Options in the Management of Olanzapine-Associated Weight Gain
Annals of Pharmacotherapy, 2005
T he newer atypical antipsychotics have the advantages of improved efficacy for negative symptoms, with reduced incidence of adverse effects, such as extrapyramidal side effects and tardive dyskinesias, compared with firstgeneration antipsychotics. One of the most frequently reported adverse effects with these newer agents is weight gain. 1 The increased health risks associated with weight gain-namely, coronary heart disease, diabetes, hypertension, and dyslipidemia-with continued therapy pose a challenge to clinicians. An additional concern is the risk of relapse with medication nonadherence in response to olanzapine-associated weight gain. 2 Obesity, defined by the National Heart, Lung, and Blood Institute as a body mass index (BMI) >30 kg/m 2 , is a serious medical problem in the US, affecting 1 of 4 Americans. 3 Patients with schizophrenia have a higher risk for obesity than does the general population. 4 Mechanism of Weight Gain The specific mechanism(s) by which weight gain develops with novel antipsychotic therapy is not known; however, increased levels of dopamine, serotonin (5-HT), and norepinephrine in the hypothalamus have been associated with satiety. 5 Atypical antipsychotics have variable binding affinities for dopamine, serotonin, and α-adrenergic, histaminergic, and muscarinic receptors (Table 1). 2,5,6 Data suggest that antagonism of neurotransmitter receptors