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No association or linkage between polymorphisms in the genes encoding cholecystokinin and the cholecystokinin B receptor and panic disorder

Molecular Psychiatry volume 6, pages 59–65 (2001)Cite this article

Abstract

Growing animal data implicate cholecystokinin in the regulation of anxiety, while human clinical research confirms the role of cholecystokinin in the provocation of panic attacks. Antipanic medications suppress the ability of cholecystokinin to induce panic attacks, and may alter the expression of the cholecystokinin gene. Thus, there is increased interest in understanding the molecular genetic component of these observations. Recent association studies using persons with panic disorder described some association between polymorphisms in the genes encoding cholecystokinin and the cholecystokinin B-receptor and panic disorder. In this study, we used a family-based design, employing 596 individuals in 70 panic disorder pedigrees, as well as 77 haplotype relative risk ‘triads’. Subjects were genotyped for two polymorphisms: the polymorphic microsatellite marker in the CCK-BR locus using PCR-based genotyping and at a single nucleotide polymorphism in the CCK promoter using a fluorescence polarization detection assay, and the data were analyzed for genetic association and linkage. Employing a variety of diagnostic and genetic models, linkage analysis produced no significant lod scores at either locus. Family-based tests of association, the haplotype-based haplotype relative risk statistic and the transmission disequilibrium test, were likewise non-significant. The results reported here provide little support for the role of these polymorphisms in panic disorder.

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Acknowledgements

The authors would like to thanks Xiangning Chen (CuraGen Genomics, New Haven, CT, USA) and Yan Zhang-Klompus (LJL BioSystems) for helpful discussion about FP-TDI and the rest of the staff at LJL BioSystems for the loan of the Analyst AD high-throughput detection platform. We also acknowledge the invaluable contribution made by the families who participated in this study. This study was supported by grants from the NIMH: MH28274 (MMW), MH37592 (AJF), MH30906 (DFK), and MH48858 (SEH); and from the National Alliance for Research on Schizophrenia and Depression (SPH).

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Authors and Affiliations

  1. Department of Psychiatry, College of Physicians and Surgeons at Columbia University and the New York State Psychiatric Institute, USA

    S P Hamilton, S L Slager, L Helleby, G A Heiman, D F Klein, S E Hodge, M M Weissman, A J Fyer & J A Knowles

  2. Division of Biostatistics, Columbia University, USA

    S E Hodge

  3. Mailman School of Public Health, Columbia University, USA

    M M Weissman

  4. Columbia Genome Center, College of Physicians and Surgeons at Columbia University, USA

    J A Knowles

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  1. S P Hamilton
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Correspondence to J A Knowles.

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Hamilton, S., Slager, S., Helleby, L. et al. No association or linkage between polymorphisms in the genes encoding cholecystokinin and the cholecystokinin B receptor and panic disorder. Mol Psychiatry 6, 59–65 (2001). https://doi.org/10.1038/sj.mp.4000788

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