Genetic biomarkers tag antipsychotic weight gain

Weight gain is one of the unfortunate side effects from second-generation antipsychotic drugs. It affects almost half of the patients who take them, and has an impact on their likelihood of sticking with the treatment, as well as their future metabolic health. Researchers from the Canadian Centre for Addiction and Mental Health (CAMH) have found two genetic biomarkers that tie in with this rapid weight gain, and that could lead to personalized treatment.

In a genome-wide association study (GWAS), published in the Archives of General Psychiatry, researchers found that children and young people with two copies of a genetic variation near the melanocortin-4 receptor (MC4R) gene, a gene known to be linked to weight and appetite, gained around three times as much weight as those with no copies or one copy.

"The weight gain was associated with this genetic variation in all these groups, which included pediatric patients with severe behavior or mood problems, and patients with schizophrenia experiencing a first episode or who did not respond to other antipsychotic treatments," says CAMH scientist Daniel Müller.

In another CAMH study, published earlier this year in The Pharmacogenomics Journal, researchers spotted another variation on the MC4R gene. Müller adds: "We don't know exactly how the atypical antipsychotics disrupt this pathway, or how this variation affects the receptor. We need further studies to validate this result and eventually turn this into a clinical application."

Knowing who is likely to be affected by rapid weight gain could help doctors prepare patients for this outcome, or tailor the treatment to the patient, selecting alternative forms of treatment. Knowing the mechanism could also point the way toward treatments with fewer side effects.

- read the press release
- see the abstract in Archives of General Psychiatry
- check out the abstract in The Pharmacogenomics Journal

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