Genetics May Explain Why Some Drugs Cause Weight Gain

Although weight gain is often associated with the use of antipsychotic drugs, not all schizophrenia or bipolar patients taking them gain a lot of weight. In fact, at most only about half of them do. Thus, there is reason to suspect that antipsychotic-induced obesity might be due, at least in part, to a genetic susceptibility.

Yvon Chagnon, Ph.D., a molecular biologist and director of the Genomic Laboratory at Laval University in Beauport, Quebec, Canada, and his colleagues have confirmed that suspicion. They reported in the December Molecular Psychiatry that they found a gene variant associated with antipsychotic-induced obesity in a particular region of chromosome 12.

Chagnon and his coworkers performed gene scans on more than 500 persons who had either schizophrenia or bipolar disorder or who were relatives of individuals with schizophrenia or bipolar disorder—that is, on 21 multigenerational families. The scientists then learned that out of these some 500 persons, 128 were being treated with antipsychotics, and of the 128 on antipsychotics, 39 (30 percent) were obese.

The researchers then determined that, of the 39 individuals who were taking antipsychotics and who were obese, 31 belonged to families in which two or more members on antipsychotics were also obese. In other words, nine out of the original 21 multigenerational families had two or more members who were taking antipsychotics and were obese.

The investigators then submitted genetic information from members of these nine multigenerational families to linkage analysis to determine whether they could find a link between antipsychotic-induced obesity and a particular gene variant.

A variant of a particular stretch of DNA on chromosome 12 was found to be associated with antipsychotic-induced obesity. Thus this region, or a gene nearby, might be partially responsible for the condition, the scientists believe. Moreover, the DNA patch is located very close to a gene known to control food intake and energy expenditure.

These results have practical implications for clinical psychiatrists. The main application, Chagnon told Psychiatric News, is to develop a genetic test that can be used to identify patients susceptible to antipsychotic-induced weight gain.

“A better understanding of the pathophysiology of weight gain associated with antipsychotics could also facilitate a better treatment of this crippling effect, as well as lead to the development of new antipsychotics devoid of this side effect,” Marc-André Roy, M.D., an assistant professor of psychiatry at the University of Laval and one of the study authors, added.

An abstract of the study, “A Genomewide Linkage Study of Obesity as Secondary Effect of Antipsychotics in Multigenerational Families of Eastern Quebec Affected by Psychoses,” is posted online at<www.nature.com/cgi-taf/DynaPage.taf?file=/mp/journal/v9/n12/abs/4001537a.html>.▪