Psychiatric News January 7, 2005
Volume 40 Number 1
© 2005 American Psychiatric Association
p. 32
Genetics May Explain Why Some Drugs Cause Weight Gain
Joan Arehart-Treichel
Certain people may gain weight when taking antipsychotics because they
have inherited a particular gene variant. This discovery may be a first step
toward using a genetic test to identify such individuals.
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>.
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