الفهرس 
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Abstract
Schizophrenia (SZ) is a debilitating mental disorder that presents impairments in neurocognition and social cognition. There is a growing interest in metabolic alterations in patients with psychiatric disorders due to their increased risk for metabolic syndrome development. Antipsychotic drugs usually prescribed for the treatment of schizophrenia have recently been found to be associated with risk factors of metabolic syndrome such as hypertension, obesity, insulin resistance, low level of HDL-C and high levels of triacylglycerols (TAG). The clustering of these factors may contribute in the development of diabetes mellitus and coronary artery disease. However, the pathophysiological mechanisms underlying metabolic side effects are not fully understood. Atypical antipsychotic (AAP)-induced weight gain has been the primary focus of attention because obesity is an easily detectable side effect, and researchers have assumed that the initiating pathophysiology is weight gain. Obesity is known to predispose individuals to develop dyslipidemia and glucose intolerance. Thus, it is conceivable that AAP-associated metabolic disturbances are associated with weight gain. Energy homeostasis and 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. It has been suggested that Atypical antipsychotics (AAPs) interact with the complex system of neurotransmitters, neuropeptides, and other modulators in brain neuronal circuits involving the hypothalamus and brain stem where a neuropeptidergic network mediates the actions of leptin and ghrelin to provoke disturbances in energy homeostasis, endocrine alterations, and BW control. There are strong links between oxidative stress anomalies and the pathophysiology of schizophrenia, indicated by the increased lipid peroxidation products in plasma and red cells, altered levels of both enzymatic and non-enzymatic antioxidants in schizophrenic patients. In this way, the main markers of the lipid peroxidation processes in our study include malondialdehyde (MDA). On the other side, the potential toxicity of free radicals is counteracted by a number of cytoprotective antioxidant enzymes that limit the damage, such as catalase.
The present study aimed to assess the effect of three widely-used APs, namely olanzapine (OLZ), quetiapine (QUET), and risperidone (RIS) on body weight, and its relation with appetite hormones, metabolic markers, and oxidative stress, in SZ AP-naïve men.
This study included 40 male subjects divided into:
1- Patients group: consisted of 25 male drug-naïve schizophrenic patients) age ranged from 18 to 47 years; 27.8±8.3). The patients were attending inpatients in the institute of psychiatry-neuropsychiatry department, Ain Shams University Hospitals in Cairo, Egypt. Patients were medically indicated into three groups for initiation of treatment with OLZ (10 patients receiving 10 mg/day), QUET (6patients receiving 600 mg/day), or RIS (9 patients receiving 6 mg/day). The diagnosis of schizophrenia was performed following the criteria of the ICD-10. All patients received electroconvulsive therapy (ECT) (6 – 8 sessions).
2-Control group: including 15 healthy males subjects without current or past psychiatric disorders were included and served as controls. Both groups were matching regarding age and gender.
All subjects underwent fasting (12 hours) blood collection and anthropometric measurements (Body Mass Index; BMI) at interval different times. BMI, leptin, ghrelin and routine monitoring of fasting blood glucose and lipid profile were examined at baseline and after 2, 4, and 8 weeks, while MDA and catalase were measured at baseline and after 4, and 8 weeks of treatment.
Biochemical parameters:
Sera and plasma were subjected to the following:
• Detection of serum leptin using ELISA.
• Detection of serum ghrelin using ELISA.
• Determination of serum malondialdehyde
• Detection of plasma catalase enzyme.
• Estimation of plasma glucose.
• Estimation of lipid profile: TAG, cholesterol, HDL-C, LDL-C, VLDL-C
The results of the present study showed that, at the baseline characteristics, there were no statistically significant differences between the schizophrenic and control groups, except that cholesterol, LDL-C, and catalase showed a statistically significant decrease compared to controls. After the treatment, in both the olanzapine (OLZ) and quetiapine (QUET) groups the degree of change amplified by time, reaching maximum after 8 weeks. There was a statistically significant increase in BMI, leptin, gherlin, glucose, lipids profile, and oxidative stress parameters (malondialdehde and catalase). The increases were more pronounced in the OLZ treated patients compared to those receiving QUET. On the other hand, as for the treatment with RIS, there was little or no changes through the treatment period compared to the control group. The results showed a positive relationship between BMI with leptin and glucose, lipid profile and malondialdehde. The results also showed a positive relationship between leptin with total cholesterol, LDL-C, HDL-C, TAG and malondialdehde in descending order. On the other hand, there was a negative relationship between leptin and HDL-C.
The use of reference change values showed an increase in the BMI from its baseline value in 80%, 33%, 0% of patients treated with olanzapine (OLZ), quetiapine (QUET), and risperidone (RIS), respectively. This study showed that serum leptin levels increased in 100% of patients treated with OLZ and increased in 83% and 11% of patients treated with the QUET, and RIS respectively. The study showed reduction in the hormone ghrelin from the baseline in 83%, 60%, 44% of patients treated with drugs QUET, OLZ, and RIS respectively. Also the study showed elevated fasting blood sugar in 70%, 67%, 22% of the patients treated with drugs OLZ and QUET and RIS in order. Also, total cholesterol increased in 100%, 67%, 0% of patients treated with the drugs OLZ, QUET and RIS respectively. The high concentration of TAG was found in 80%, 67% of patients treated with the drugs OLZ and QUET respectively, while patients treated with RIS showed no change in the value of TAG. The decrease in HDL-C and increase in LDL-C and VLDL-C ,were recorded in 90%, 100%, and 70% of the OLZ group, in 100%, 67%, and 67% in the QUET group, and in 89%, 22% and zero % in the RIS group respectively. A decrease in catalase level and an increase in MDA were recorded in 60% and 90% of the OLZ group, 83% and 100% of the QUET group, and in 56% and 33% of the RIS group respectively.
Conclusion: In this study the association between different AAPs used in the treatment of SZ and metabolic syndrome has been explored. These drugs effectively reduce psychotic symptoms, however they too are associated with severe side effects like weight gain and disruption of glucose metabolism that may lead to diabetes. Patients undergoing treatment with OLZ were more prone to metabolic syndrome as the drug induces weight gain, dyslipidemia and hyperglycemia after 8 weeks of treatment. QUET was found to be second most potent drug in inducing metabolic syndrome as the BMI increased along with a significant hyperglycemia and dyslipidemia after 8 weeks. RIS is comparatively safer drugs as its role in inducing metabolic abnormalities in SZ patients was insignificant, although the impact of long term administration of these drugs needs to be explored. Since antipsychotic drugs cause metabolic abnormalities, therefore regular monitoring of metabolic and cardiovascular risk factors is recommended. Monitoring should be individually tailored together with an emphasis on modification of lifestyle factor such as diet and exercise. The long term effects of these drugs and other antipsychotics drugs needs to be explored.