Weight gain is a major problem associated with long-term antipsychotic drug treatment. Clozapine is known to induce particularly profound weight gain. Although the mechanism of it is not clearly understood, the 5-HT2C receptor and leptin are implicated in its development. The present study examined the effects of 5-HT2C and leptin gene polymorphisms on weight change and obesity in the patients on clozapine.

107 patients (mean age 39.5±10.1 y.) meeting ICD-10 criteria for schizophrenia or schizoaffective disorder receiving clozapine took part in this study. The patient assessment included an interview, measures of weight, height, waist-hip ratio, waist circumference, body mass index (BMI, kg/m2); blood samples were taken for random blood glucose and genetic testing for 5-HT2C and leptin gene.

Central obesity was present in 102 patients as defined by increased waist circumference and obesity in 67 patients as defined by BMI>30. Type II diabetes was present in 8 patients and type I diabetes in one. In 93 patients (62M, 31F) we assessed change in BMI and weight during treatment which was 2.6±4.2kg/m2 and 7.43±12.35 kg, respectively.

There was no association between 759C/T 5-HT2C receptor and -2548A/G leptin gene polymorphisms with BMI or weight.

No association between 759C/T 5-HT2C receptor and -2548A/G leptin gene polymorphisms was found with change of BMI or waist circumference.

We found no significant association between 759C/T 5-HT2C receptor and -2548A/G leptin gene polymorphisms and changes in BMI or weight in the patients treated with clozapine.