Polymorphisms of the 5-HT2C receptor and leptin genes are associated with antipsychotic drug-induced weight gain in Caucasian subjects with a first-episode psychosis.
OBJECTIVE
Weight gain, leading to further morbidity and poor treatment adherence, is a common consequence of treatment with antipsychotic drugs. Two recent studies in the same cohort of Chinese Han subjects have shown that polymorphisms of the promoter regions of both the serotonin 5-hydroxytryptamine 2C (5-HT2C) receptor and the leptin genes, are associated with antipsychotic-induced weight gain over 10 weeks. We have investigated whether these effects remain true in a Caucasian population and following longer term treatment.


METHODS
Seventy-three Spanish caucasian patients with a first-episode psychosis and initially drug-naive were genotyped for the 5-HT2C receptor -759C/T and leptin -2548A/G polymorphisms. Body mass index and plasma leptin levels were monitored after 6 weeks, 3 months and 9 months of antipsychotic treatment.


RESULTS
Patients with the -759T variant allele showed significantly less weight gain than those without this allele. This effect held true in the smaller group of patients receiving olanzapine. The -2548 leptin polymorphism was not associated with short-term (6 week and 3 month) weight increases but did show significant association with 9-month antipsychotic-induced weight gain. The 5-HT2C -759 genotype was significantly associated with pre-treatment plasma leptin levels.


CONCLUSIONS
These findings confirm the importance of two genetic factors associated with long-term antipsychotic-induced weight increases in schizophrenia, and implicate a role for leptin in the 5-HT receptor-mediated weight regulation.
Templeman
Lucy A
LA
Division of Psychiatry and Neuroscience, Queen's University Belfast, Whitla Medical Building, 97 Lisburn Road, Belfast BT9 7BL, UK.
Reynolds
Gavin P
GP
Arranz
Belen
B
San
Luis
L
D000328:Adult; D000341:Affective Disorders, Psychotic / Q000150:complications / Q000188:drug therapy*; D000483:Alleles; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000494:pharmacology*; D001569:Benzodiazepines / Q000494:pharmacology; D015992:Body Mass Index; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D020738:Leptin / Q000097:blood / Q000235:genetics*; D008297:Male; D008957:Models, Genetic; D000077152:Olanzapine; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D044405:Receptor, Serotonin, 5-HT2C / Q000235:genetics*; D054411:Receptors, Leptin; D012559:Schizophrenia / Q000188:drug therapy; D013997:Time Factors; D015430:Weight Gain / Q000187:drug effects* / Q000235:genetics
D014150:Antipsychotic Agents; C515448:LEPR protein, human; D020738:Leptin; D044405:Receptor, Serotonin, 5-HT2C; D054411:Receptors, Leptin; D001569:Benzodiazepines; D000077152:Olanzapine