Physiogenomic comparison of weight profiles of olanzapine- and risperidone-treated patients

G. Ruão, J. W. Goethe, C. Caley, S. Woolley, T. R. Holford, M. Kocherla, A. Windemuth, J. D. Leon

Research output: Contribution to journalArticlepeer-review

57 Scopus citations


Atypical antipsychotics induce pre-diabetic symptoms in some but not all patients, characterized most notably by elevated weight. The side effect profiles of the various drugs in the class differ, however, raising the possibility of drug-specific mechanisms for similar side effects. We used physiogenomic analysis, an approach previously employed to study the genetics of drug and diet response, to discover and compare genetic associations with weight profiles observed in patients treated with olanzapine and risperidone as an approach to unraveling contrasting mechanistic features of both drugs. A total of 29 single nucleotide polymorphisms (SNPs) were selected from 13 candidate genes relevant to two potential pharmacological axes of psychotropic-related weight profiles, appetite peptides and peripheral lipid homeostasis. We applied physiogenomic analysis to a cross-section of 67 and 101 patients being treated with olanzapine and risperidone, respectively, and assessed genetic associations with the weight profiles. Weight profiles in patients treated with olanzapine were significantly associated with SNPs in the genes for apolipoprotein E, apolipoprotein A4 and scavenger receptor class B, member 1. Weight profiles in patients treated with risperidone were significantly associated with SNPs in the genes for leptin receptor, neuropeptide Y receptor Y5 and paraoxonase 1. These results are consistent with contrasting mechanisms for the weight profile of patients treated with these drugs. Genes associated with olanzapine weight profiles may be related to peripheral lipid homeostatic axes, whereas those associated with risperidone's may be related to brain appetite peptide regulation. Future physiogenomic studies will include neurotransmitter receptor SNPs and validation in independent samples.

Original languageEnglish
Pages (from-to)474-482
Number of pages9
JournalMolecular Psychiatry
Issue number5
StatePublished - May 2007

Bibliographical note

Funding Information:
This research was supported in part by NIH Small Business Innovation Research Grant 1 R43 MH073291-01 ‘Gene Markers: Antipsychotic-Induced Metabolic Syndrome’ to Genomas, Inc. Principal investigator is G Ruaño, MD, with a subcontract to J Goethe, MD. The work at the Mental Health Research Center at Eastern State Hospital was supported by internal research funding from J de Leon, MD. In the past 2 years, J de Leon, MD. has been on the advisory board of Bristol-Myers Squibb and Roche Molecular Systems Inc.; he received investigator-initiated grants from Roche Molecular Systems Inc. and the E Lilly Research Foundation; he has lectured once supported by E Lilly, once supported by Bristol–Myers Squibb, twice supported by Janssen and five times by Roche Molecular Systems Inc. We are thankful to G Pearlson, MD, Institute of Living, Hartford, CT, USA, for his contribution to our neuropsychiatric research programs. We are grateful to M Johnson, RN, MT Susce, RN, MLT, B Szarek, RN and E Murray-Carmichael, BSc, who helped with recruitment of patients and establishment of the DNA repository.


  • Antipsychotic agents
  • Appetite
  • Lipid metabolism
  • Obesity
  • Pharmacogenetics

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Molecular Biology


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