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Systematic analysis of dopamine receptor genes (DRD1–DRD5) in antipsychotic-induced weight gain

The Pharmacogenomics Journal volume 12, pages 156–164 (2012)Cite this article

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Abstract

Antipsychotic-induced weight gain has emerged as a serious complication in the treatment of patients with most antipsychotics. We have conducted the first in-depth examination of dopamine receptor genes in antipsychotic-induced weight gain. A total of 206 patients (139 of European descent and 56 African Americans) who underwent treatment for chronic schizophrenia or schizoaffective disorder were evaluated after on average over 6 weeks of treatment. Thirty-six tag single nucleotide polymorphisms (SNPs) and one variable-number tandem repeat, spanning the five dopamine receptor genes (DRD1–DRD5) were analyzed. In the total sample, we found a nominally significant association between the DRD2 rs1079598 marker and weight change using a cutoff of 7% gain (P=0.03). When stratifying the sample according to ethnicity and antipsychotics with highest risk for weight gain, we found significant associations in three DRD2 SNPs: rs6277 (C957T), rs1079598 and rs1800497 (TaqIA). The other genes were primarily negative. We provide evidence that dopamine receptor DRD2 gene variants might be associated with antipsychotic-induced weight gain in chronic schizophrenia patients.

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Acknowledgements

This study was supported by CIHR operational grants to JLK (MOP-15007) and DJM (MOP-89853); NARSAD Young Investigator Award to DJM; CIHR postdoctoral Wyeth fellowship to AKT and RPS; MH41468, the Prentiss Foundation, Ritter Foundation, Hintz family and the Peterson Family to HYM; the Bebensee fellowship to CCZ. We thank Dr I Puls for support in patient recruitment. We also thank the participants in this study.

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  1. D J Müller and C C Zai: These authors contributed equally to this work.

Authors and Affiliations

  1. Neuroscience Department, Neurogenetics Section, Centre for Addiction and Mental Health, Toronto, Ontario, Canada

    D J Müller, C C Zai, M Sicard, E Remington, R P Souza, A K Tiwari, R Hwang, O Likhodi, S Shaikh, N Freeman & J L Kennedy

  2. Clinical Research Department, Biostatistical Consulting Service, Centre for Addiction and Mental Health, Toronto, Ontario, Canada

    D J Müller & T Arenovich

  3. Department of Psychiatry, Charité University Medicine Berlin, Campus Mitte, Berlin, Germany

    A Heinz

  4. Psychiatric Hospital, Vanderbilt University, Nashville, TN, USA

    H Y Meltzer

  5. Department of Psychiatry, College of Physicians and Surgeons, Columbia University and The New York State Psychiatric Institute, New York, NY, USA

    J A Lieberman

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Correspondence to D J Müller or J L Kennedy.

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Competing interests

DJM, CCZ, MS, EL, RPS, AKT, RH, NF, SS, OL, AH reported no competing interests. HYM has received grants or is a consultant to: Abbott Labs, ACADIA, Bristol-Myers Squibb, Eli Lilly, Jansse, Pfizer, AstraZeneca, GlaxoSmithKline, Memory, Cephalon, Minster, Aryx and BiolineRx. HYM is a shareholder of ACADIA. JAL reports having received research funding or consulting or educational fees from Allon, AstraZeneca, Bioline, Bristol-Myers Squibb, Eli Lilly, Forest Labs, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Solvay and Wyeth. JLK has been a consultant to GSK, Sanofi-aventis, Dainippon-Sumitomo.

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Müller, D., Zai, C., Sicard, M. et al. Systematic analysis of dopamine receptor genes (DRD1–DRD5) in antipsychotic-induced weight gain. Pharmacogenomics J 12, 156–164 (2012). https://doi.org/10.1038/tpj.2010.65

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