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Possible Genetic Linkage Cited in Antipsychotic Drug Weight Gain

There appears to be a genetic basis for the weight gain associated with use of antipsychotic drugs among patients with schizophrenia.

Dr. Gavin Reynolds and colleagues at the Department of Biomedical Science, University of Sheffield, Sheffield, England, carried out their research because increased body fat is a side-effect of treatment with antipsychotic drugs for schizophrenia. This often leads to further medical problems associated with obesity, as well as poor adherence to treatment.

This drawback has become apparent with the introduction of new atypical antipsychotics; two drugs, clozapine and olanzapine, are known to induce substantial weight gain. Treatment with most other antipsychotics, both classic and atypical, produces some weight gain.

The serotonin receptor 5-hydroxytryptamine 2C receptor (5-HT2C) has been associated with this effect. Investigators aimed to establish whether a genetic alteration of the promoter region of this receptor affects weight gain after drug treatment.

Dr Reynolds and colleagues enrolled 123 Chinese in-patients with first-time schizophrenia. Patients received conventional treatment with antipsychotic drugs, in most cases chlorpromazine and risperidone, were given a standard hospital diet, and underwent blood testing to identify 5-HT2C receptor gene status.

After six weeks, 28 percent of patients with the wild type (most common) genotype had an increased bodyweight of seven percent or more compared with none of the patients with the variant (-759T) allele. At 10 weeks, the corresponding proportions were 51 percent for the wild type genotype and 15 percent for the variant.

Dr Reynolds in a separate comment on their study said: "We have identified a genetic factor that indicates the likelihood of developing a serious side effect of psychiatric drug treatment. If confirmed, these findings could provide the basis for a simple test to determine a patient's liability to develop drug-induced weight gain, and assist the doctor in choosing the most appropriate drug treatment.

"Such predictive tests are likely to be common in the surgery of the future, where genetic profiling would be used to indicate the most effective and least harmful treatment, individualized for the patient."
Lancet 2002; 359: 2086-87.

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