Genetic link to rapid weight gain from antipsychotics discoveredJuly 18, 2012
Toronto - Scientists have discovered two genetic variants associated with the substantial, rapid weight gain occurring in nearly half the patients treated with antipsychotic medications, according to two studies involving the Centre for Addiction and Mental Health (CAMH).
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.
"Weight gain occurs in up to 40 per cent of patients taking medications called second-generation or atypical antipsychotics, which are used because they're effective in controlling the major symptoms of schizophrenia," says CAMH Scientist Dr. James Kennedy, senior author on the most recent study published online in the Archives of General Psychiatry.
This weight gain can lead to obesity, type 2 diabetes, heart problems and a shortened life span. "Identifying genetic risks leading to these side-effects will help us prescribe more effectively," says Dr. Kennedy, head of the new Tanenbaum Centre for Pharmacogenetics, which is part of CAMH's Campbell Family Mental Health Research Institute. Currently, CAMH screens for two other genetic variations that affect patients' responses to psychiatric medications.
Each study identified a different variation near the melanocortin-4 receptor (MC4R) gene, which is known to be linked to obesity.
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 6 kg versus 2 kg.) The study had four patient groups: two from the U.S., one in Germany and one from a larger European study.
"The weight gain was associated with this genetic variation in all these groups, which included pediatric patients with severe behaviour or mood problems, and patients with schizophrenia experiencing a first episode or who did not respond to other antipsychotic treatments," says CAMH Scientist Dr. Daniel Müller. "The results from our genetic analysis combined with this diverse set of patients provide compelling evidence for the role of this MC4R variant. Our research group has discovered other gene variants associated with antipsychotic-induced weight gain in the past, but this one appears to be the most compelling finding thus far."
Three of the four groups had never previously taken atypical antipsychotics. Different groups were treated with drugs such as olanzapine, risperidone, aripiprazole or quetiapine, and compliance was monitored to ensure the treatment regime was followed. Weight and other metabolic-related measures were taken at the start and during treatment.
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, NY. In this type of study, variations are sought across a person's entire set of genes to identify those associated with a particular trait. The result pointed to the MC4R gene.
This gene's role in antipsychotic-induced weight gain had been identified in a CAMH study published earlier this year in The Pharmacogenomics Journal, involving Drs. Müller and Kennedy, and conducted by PhD student Nabilah Chowdhury. They found a different variation on MC4R that was linked to the side-effect.
For both studies, CAMH researchers did genotyping experiments to identify the single changes to the sequence of the MC4R gene - known as single nucleotide polymorphisms (SNPs) - related to the drug-induced weight gain side-effect.
The MC4R gene encodes a receptor involved in the brain pathways regulating weight, appetite and satiety. "We don't know exactly how the atypical antipsychotics disrupt this pathway, or how this variation affects the receptor," says Dr. Müller. "We need further studies to validate this result and eventually turn this into a clinical application."
The CAMH researchers were supported by a Canadian Institutes of Health Research (CIHR) grant and a NARSAD grant from the U.S. Brain and Behavior Fund.
Centre for Addiction and Mental Health
Related Weight Gain Current Events and Weight Gain News Articles
Lipid testing underutilized in adults taking antipsychotic medications
Too few adults taking antipsychotic medications are being screened for abnormalities in lipids, which include cholesterol and triglycerides, new research from the University of Colorado Anschutz Medical Campus finds.
As early as first grade, children with severe obesity are more likely to be ostracized
Childhood obesity has almost quadrupled among 6- to 11-year-olds since 1980. Today, approximately one in 20 children in the United States is severely obese and this public health threat costs the U.S. government billions of dollars annually.
Telephone-based cognitive behavioral therapy significantly improves menopause symptoms
Chatting on the phone with a "sleep coach" and keeping a nightly sleep diary significantly improve sleep quality and reduce insomnia in women through all stages of menopause, according to a new study published today in JAMA Internal Medicine.
New study evaluates nicotine's relationship to body weight and food intake
A study published today in Nicotine & Tobacco Research demonstrates in a carefully controlled series of studies that the self-administration of nicotine by rats suppresses body weight gain independent of food intake.
Exercise, more than diet, key to preventing obesity
Two factors--metabolism and gut microbes - have been credited by researchers as key players in the fight against obesity. However, there is an ongoing debate about whether exercise or diet better promotes metabolism and healthy shifts in gut microbes, the microscopic organisms in our intestines that break down food and can contribute to decreased obesity.
No link between eating dinner after 8pm and obesity in children
Researchers at King's College London have found no significant link between eating the evening meal after 8pm and excess weight in children, according to a paper published this month in the British Journal of Nutrition.
Physical activity is 'magic bullet' for pandemics of obesity and cardiovascular disease
In an editorial published in the current issue of Cardiology, professors from the Charles E. Schmidt College of Medicine at Florida Atlantic University have evaluated the totality of evidence and conclude that regular physical activity bears the closest resemblance to a "magic bullet" to combat the worldwide epidemic of obesity and cardiovascular disease.
National study shows new ways to stop weight gain cut young adults' obesity risk by half
A new study has identified two self-regulation strategies effective in preventing weight gain among young adults.
Study identifies successful weight-gain prevention strategies for young adults
Scientists funded by the National Heart, Lung, and Blood Institute have identified strategies that might help young adults (aged 18 to 35 years) avoid weight gain.
Compound from hops lowers cholesterol, blood sugar and weight gain
A recent study at Oregon State University has identified specific intake levels of xanthohumol, a natural flavonoid found in hops, that significantly improved some of the underlying markers of metabolic syndrome in laboratory animals and also reduced weight gain.
More Weight Gain Current Events and Weight Gain News Articles