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Obesity and metabolic syndrome are significant problems for patients
taking antipsychotic drugs. Evidence is emerging of genetic risk
To investigate the influence of two candidate genes, smoking and drug
treatment on obesity and metabolic syndrome in patients with
Patients (n=134) were assessed for measures of obesity, other factors
contributing to metabolic syndrome, and two genetic polymorphisms
(5-HT2C receptor −759C/T and leptin −2548A/G).
Neither genotype nor smoking was significantly associated with measures
of obesity. However, both leptin genotype and smoking were significantly
associated with metabolic syndrome. Significant interaction occurred
between the genetic polymorphisms for effects on obesity, whereby a
genotype combination increased risk. Drug treatment showed significant
effects on measures of obesity and triglyceride concentrations;
risperidone was associated with lower values than olanzapine or
The findings suggest interacting genetic risk factors and smoking
influence development of metabolic syndrome in patients on antipsychotic
Weight gain is a common consequence of antipsychotic drug treatment and can lead to further morbidity.
To assess the effects of antipsychotic drug therapy on abdominal fat deposition, on insulin and leptin secretion, and on circulating glucose and lipids.
Abdominal body fat was determined by magnetic resonance imaging in a group of previously untreated patients with schizophrenia, before and after 10 weeks'antipsychotic drug treatment. Body mass and blood concentrations of glucose, insulin, leptin and lipids were also measured.
Significant increases in both subcutaneous and intra-abdominal fat were identified after antipsychotic drug treatment. A three-fold increase in leptin secretion as well as significant increases in levels of circulating lipids and non-fasting glucose were also identified.
Patients first receiving antipsychotic drugs experience substantial deposition of both subcutaneous and intra-abdominal fat, reflecting a loss of the normal inhibitory control of leptin on body mass. Along with fat deposition, the increase in levels of fasting lipids and in non-fasting glucose may provide early signs of drug-induced progression towards the metabolic syndrome.