Singapore: Two studies conducted at the Centre for Addiction and Mental Health (CAMH) have discovered two genetic variants associated with the substantial, rapid weight gain occurring in nearly half the patients treated with antipsychotic medications. These results could eventually be used to identify which patients have the variations, enabling clinicians to choose strategies to prevent this serious side-effect and offer more personalized treatment.
Each study identified a different variation near the melanocortin-4 receptor (MC4R) gene, which is known to be linked to obesity. The CAMH researchers are supported by a Canadian Institutes of Health Research (CIHR) grant and a NARSAD grant from the US Brain and Behavior Fund.
In the Archives of General Psychiatry study, people carrying two copies of a variant gained about three times as much weight as those with one or no copies, after six to 12 weeks of treatment with atypical antipsychotics. The difference was approximately six kilograms as compared to two kilograms. The study had four patient groups, including two from the US, one in Germany and one from a larger European study.
A genome-wide association study was conducted on pediatric patients by the study's lead researcher, Dr Anil Malhotra, at the Zucker Hillside Hospital in Glen Oaks. In this study, variations were sought across a person's entire set of genes to identify those associated with a particular trait. The result pointed to the MC4R gene again.
Dr James Kennedy, scientist at the CAMH and a senior author on the most recent study published online in the Archives of General Psychiatry, said that, "Weight gain occurs in up to 40 percent of patients taking medications called second-generation or atypical antipsychotics, which are used because they're effective in controlling the major symptoms of schizophrenia."
