Navigation Links
Genetic link to rapid weight gain from antipsychotics discovered
Date:7/17/2012

July 17, 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 Mller. "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. Mller 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. Mller. "We need further studies to validate this result and eventually turn this into a clinical application."


'/>"/>

Contact: Michael Torres
media@camh.ca
416-595-6015
Centre for Addiction and Mental Health
Source:Eurekalert

Related biology news :

1. Nearby chimpanzee populations show much greater genetic diversity than distant human populations
2. Will a genetic mutation cause trouble? Ask Spliceman
3. UC Santa Barbara researchers discover genetic link between visual pathways of hydras and humans
4. Perception and preference may have genetic link to obesity
5. A foot in the door to genetic information
6. Genetic survey of endangered Antarctic blue whales shows surprising diversity
7. Epigenetic signatures direct the repair potential of reprogrammed cells
8. Epigenetics and epidemiology -- hip, hype and science
9. Genetic variation in East Asians found to explain resistance to cancer drugs
10. First complete full genetic map of promising energy crop
11. Genetic research develops tools for studying diseases, improving regenerative treatment
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:5/16/2016)... , May 16, 2016   EyeLock LLC ... today announced the opening of an IoT Center of ... strengthen and expand the development of embedded iris biometric ... unprecedented level of convenience and security with unmatched biometric ... one,s identity aside from DNA. EyeLock,s platform uses video ...
(Date:4/28/2016)... BANGALORE, India , April 28, 2016 /PRNewswire/ ... product subsidiary of Infosys (NYSE: INFY ), and ... global partnership that will provide end customers with ... banking and payment services.      (Logo: http://photos.prnewswire.com/prnh/20130122/589162 ... area for financial services, but it also plays a fundamental ...
(Date:4/19/2016)... April 20, 2016 The new ... a compact web-based "all-in-one" system solution for all door ... reader or the door interface with integration authorization management ... control systems. The minimal dimensions of the access control ... the building installations offer considerable freedom of design with ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... ... June 23, 2016 , ... Charm Sciences, Inc. is ... has received AOAC Research Institute approval 061601. , “This is another AOAC-RI approval ... Bob Salter, Vice President of Regulatory and Industrial Affairs. “The Peel Plate methods ...
(Date:6/23/2016)... ... June 23, 2016 , ... Supplyframe, the Industry ... Supplyframe Design Lab . Located in Pasadena, Calif., the Design Lab’s mission ... hardware projects are designed, built and brought to market. , The Design Lab ...
(Date:6/23/2016)...  Blueprint Bio, a company dedicated to identifying, protecting ... has closed its Series A funding round, according to ... "We have received a commitment from Forentis Fund that ... meet our current goals," stated Matthew Nunez . ... complete validation on the current projects in our pipeline, ...
(Date:6/23/2016)... WI (PRWEB) , ... June 23, 2016 , ... ... focused on quality, regulatory and technical consulting, provides a free webinar ... presented on July 13, 2016 at 12pm CT at no charge. , Incomplete ...
Breaking Biology Technology: