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Effect of COMT Val108/158Met Genotype on Risk for Polydipsia in Chronic Patients with Schizophrenia

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Abstract

Polydipsia is a serious condition often seen among patients with schizophrenia (SCZ). The cause of polydipsia is unknown; hence, it is hard to treat or manage. Animal studies showed that the drinking behavior is regulated by central dopaminergic neurotransmission at the hypothalamus. Meanwhile, the existence of a genetic predisposition to polydipsia in patients with SCZ has been suggested. The purpose of this study was to assess whether a functional polymorphism, Val108/158Met in the gene for catechol-O-methyltransferase (COMT), is associated with susceptibility to polydipsia using a Japanese sample of SCZ. Our sample includes 330 chronic patients with SCZ (83 polydipsic patients and 247 non-polydipsic controls). The common COMT Val108/158Met polymorphism was genotyped, and the differences in genotype distribution and allele frequency between cases and controls were evaluated using the χ 2 test. A significant association between the COMT Val108/158Met polymorphism and polydipsia was found (genotype distribution: χ 2 = 13.0, df = 2, p = 0.001; allele frequency: χ 2 = 7.50, df = 1, p = 0.006). The high-COMT activity group (Val/Val) was more frequent among patients with polydipsia compared with the low-COMT activity group (Val/Met + Met/Met) [odds ratio (OR) = 2.46]. The association survived after controlling for other possible confounding factors, including gender, age, age of onset, current antipsychotic dose, and smoking status. Our results suggest that the COMT Val108/158Met genotype may confer susceptibility to polydipsia in SCZ. To our knowledge, this is the first association study between the COMT gene and polydipsia in SCZ. Further studies with larger sample sizes are warranted to confirm present findings.

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Acknowledgments

This work was supported in part by Grant-in-Aid Number 18591319 for Scientific Research from the Ministry of Education, Science, Sports and Culture, Japan (TS), a grant from the Japanese Society of Schizophrenia Research (TS). The authors wish to thank Ms. Kyoko Hara from the Bio-information Research Center, University of Occupational and Environmental Health, Japan, for her technical support.

Conflict of interest

Professor Jun Nakamura has received Grant support from Astellas Pharma Inc., Eli Lilly Japan K.K., GlaxoSmithKline K.K., Pfizer Japan Inc., Dainippon Sumitomo Pharma Co., Ltd., and Otsuka Pharmaceutical Co., Ltd. in 2012. Kenji Yamada, Takahiro Shinkai, Hsin-I Chen, and Kensuke Utsunomiya report no financial relationships with commercial interests.

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Authors and Affiliations

  1. Department of Psychiatry, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan

    Kenji Yamada, Takahiro Shinkai, Hsin-I Chen, Kensuke Utsunomiya & Jun Nakamura

  2. Department of Psychiatry, College of Medicine, National Taiwan University, Taipei, Taiwan

    Hsin-I Chen

  3. Principal Office Medical Center, Toshiba Human Asset Service Co., Tokyo, Japan

    Kensuke Utsunomiya

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  1. Kenji Yamada
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Correspondence to Takahiro Shinkai.

Appendix: List of Participating Hospitals (in alphabetic order)

Appendix: List of Participating Hospitals (in alphabetic order)

Chikusuikai Hospital, Ipponmatsu Suzukake Hospital, Komine Etoh Hospital, Mitate Hospital, Mojimatsugae Hospital, Nogata Nakamura Hospital, Ookawa Hospital, Shinmoji Hospital, Takayama Hospital, Tateiwa Hospital, Tsutsumi Hospital, Tsutsumikokura Hospital, Yahata Ohkura Hospital, Yukuhashikinen Hospital, and Wakato Hospital.

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Yamada, K., Shinkai, T., Chen, HI. et al. Effect of COMT Val108/158Met Genotype on Risk for Polydipsia in Chronic Patients with Schizophrenia. Neuromol Med 16, 398–404 (2014). https://doi.org/10.1007/s12017-014-8287-9

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