DRD2 promoter region variation predicts antipsychotic-induced weight gain in first episode schizophrenia.
Many antipsychotic medications carry a substantial liability for weight gain, and one mechanism common to all antipsychotics is binding to the dopamine D2 receptor. We therefore examined the relationship between -141C Ins/Del (rs1799732), a functional promoter region polymorphism in DRD2, and antipsychotic-induced weight gain in 58 first episode schizophrenia patients enrolled in a randomized trial of risperidone versus olanzapine. Carriers of the deletion allele (n=29) were compared with Ins/Ins homozygotes (noncarriers, n=29) in a mixed model encompassing 10 weight measurements over 16 weeks. Deletion allele carriers showed significantly more weight gain after 6 weeks of treatment regardless of assigned medication. Although deletion carriers were prescribed higher doses of olanzapine (but not risperidone), dose did not seem to account for the genotype effects on weight gain. Given earlier evidence that deletion carriers show reduced symptom response to medication, additional study of appropriate treatment options for these patients seems warranted.
Lencz
Todd
T
Division of Psychiatry Research,The Zucker Hillside Hospital, 75-59 263rd Street, Glen Oaks, NY 11004, USA. lencz@lij.edu
Robinson
Delbert G
DG
Napolitano
Barbara
B
Sevy
Serge
S
Kane
John M
JM
Goldman
David
D
Malhotra
Anil K
AK
D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D000077152:Olanzapine; D011401:Promoter Regions, Genetic / Q000235:genetics*; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D018967:Risperidone / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D012559:Schizophrenia / Q000188:drug therapy* / Q000235:genetics*; D015430:Weight Gain / Q000187:drug effects / Q000235:genetics*; D055815:Young Adult
D014150:Antipsychotic Agents; D017448:Receptors, Dopamine D2; D001569:Benzodiazepines; D018967:Risperidone; D000077152:Olanzapine