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Journal of Neural Transmission

, Volume 113, Issue 12, pp 1921–1925 | Cite as

Rgs 2 gene polymorphisms as modulators of anxiety in humans?

  • A. Leygraf
  • C. Hohoff
  • C. Freitag
  • S. A. G. Willis-Owen
  • P. Krakowitzky
  • J. Fritze
  • P. Franke
  • B. Bandelow
  • R. Fimmers
  • J. Flint
  • J. Deckert
Article

Summary.

Rgs2 (regulator of G-protein signalling 2) gene recently was reported as a quantitative trait gene for anxious behaviour in mice and male Rgs2 knockout mice have been shown to be more anxious than wildtype mice. Therefore we investigated four non-coding single nucleotide polymorphisms in a sample of 173 patients with panic disorder and 173 matched controls of German descent. At the genotype level all four SNPs were associated with panic disorder (p = 0.02–0.05). At the haplotype level the strongest association was observed for a haplotype containing SNP3 and SNP 4 (subgroup men and men with agoraphobia: p = 0.01 and 0.03). This points towards a functional polymorphism at the 3′ end of the gene. Our results support the hypothesis that variations of the Rgs2 gene play a role also for the development of anxiety in humans.

Keywords: Rgs2, chromosom 1q31, panic disorder, linkage disequilibrium, polymorphisms, case-control-study 

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References

  1. Crowe, RR, Goedken, R, Samuelson, S, Wilson, R, Nelson, J, Noyes, R 2001Genomewide survey of panic disorderAm J Med Genet105105109PubMedCrossRefGoogle Scholar
  2. Flint, J 2003Analysis of quantitative trait loci that influence animal behaviourJ Neurobiol544677PubMedCrossRefGoogle Scholar
  3. Gelernter, J, Bonvicini, K, Page, G, Woods, SW, Goddard, AW, Kruger, S, Pauls, DL, Goodson, S 2001Linkage genome scan for loci predisposing to panic disorder or agoraphobiaAm J Med Genet105548557PubMedCrossRefGoogle Scholar
  4. Goodwin, RD, Faravelli, C, Rosi, S, Cosci, F, Truglia, E, de Graaf, R, Wittchen, HU 2005The epidemiology of panic disorder and agoraphobia in EuropeEur Neuropsychopharmacol15435443PubMedCrossRefGoogle Scholar
  5. Hettema, JM, Neale, MC, Kendler, KS 2001A review and meta-analysis of the genetic epidemiology of anxiety disordersAm J Psychiatry15815681578PubMedCrossRefGoogle Scholar
  6. Hoehn-Saric, R, McLeod, DR, Zimmerli, WD 1991Psychophysiological response patterns in panic disorderActa Psychiatr Scand83411PubMedGoogle Scholar
  7. Huang, LJ, Durick, K, Weiner, JA, Chun, J, Taylor, SS 1997D-AKAP2, a novel protein kinase A anchoring protein with a putative RGS domainProc Natl Acad Sci USA941118411189PubMedCrossRefGoogle Scholar
  8. Mannuzza, S, Fyer, AJ, Klein, DF, Endicott, J 1986Schedule for affective disorders and schizophrenia-lifetime version modified for the study of anxiety disorders (SADS-LA): rationale and conceptual developmentJ Psychiatr Res20317325PubMedCrossRefGoogle Scholar
  9. Michael, B, Spitzer, RL, Gibbon, M, Williams, JBW 1996Structured Clinical Interview for DSM-IV Axis I Disorders, Clinical Version (SCID-CV)American Psychiatric Press, IncWashington, D.C.Google Scholar
  10. Oliviera-dos-Santos, AJ, Matsumoto, G, Snow, BE, Bai, D, Houston, FP, Whishaw, IQ, Mariathasan, S, Sasaki, T, Wakeham, A, Ohashi, PS, Roder, JC, Barnes, CA, Siderovski, DP, Penninger, JM 2000Regulation of T cell activation, anxiety, and male aggression by RGS2Proc Natl Acad Sci USA971227212277CrossRefGoogle Scholar
  11. Robins, LN, Wing, J, Wittchen, HU, Helzer, JE, Babor, TF, Burke, J, Farmer, A, Jablenski, A, Pickens, R, Regier, DA, Sartorius, N, Towle, LH 1988The composite international diagnostic interview. An epidemiologic instrument suitable for use in conjunction with different diagnostic systems and in different culturesArch Gen Psychiatry4510691077PubMedGoogle Scholar
  12. Smoller, JW, Acierno, JS, Rosenbaum, JF, Biederman, J, Pollack, MH, Meminger, S, Pava, JA, Chadwick, LA, White, C, Bulzacchelli, M, Slaugenhaupt, SA 2001Targeted genome screen of panic disorder and anxiety disorder proneness using homology to murine QTL regionsAm J Med Genet105195206PubMedCrossRefGoogle Scholar
  13. Vieland, VJ, Goodman, DW, Chapman, T, Fyer, AJ 1996New segregation analysis of panic disorderAm J Med Genet67147153PubMedCrossRefGoogle Scholar
  14. Watson, N, Linder, ME, Druey, KM, Kehrl, JH, Blumer, KJ 1996RGS family members: GTPase activating proteins for heterotrimeric G-protein alpha-subunitsNature383172175PubMedCrossRefGoogle Scholar
  15. Weissmann, MM, Bland, RC, Canino, GJ, Faravelli, C, Greenwald, S, Hwu, HG, Joyce, PR, Karam, EG, Lee, CK, Lellouch, J, Lepine, JP, Newman, SC, Oakley-Browne, MA, Rubio-Stipec, M, Wells, JE, Wickramaratne, PJ, Wittchen, HU, Yeh, EK 1997The cross-national epidemiology of panic disorderArch Gen Psychiatry54305309Google Scholar
  16. Wittchen, HU, Garczynski, E, Pfister, H 1997Composite International Diagnostic Interview according to ICD-10 and DSM-IVHogrefeGöttingenGoogle Scholar
  17. Yalcin, B, Willis-Owen, SAG, Fullerton, J, Meesaq, A, Deacon, RM, Rawlins, JNP, Copley, RR, Morris, AP, Flint, J, Mott, R 2004Genetic dissection of a behavioral quantitative trait locus shows that Rgs2 modulates anxiety in miceNat Genet36119711202PubMedCrossRefGoogle Scholar
  18. Zhao, JH, Sham, PC 2002Faster haplotype frequency estimation using unrelated subjectsHum Hered535356CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • A. Leygraf
    • 1
  • C. Hohoff
    • 1
  • C. Freitag
    • 2
  • S. A. G. Willis-Owen
    • 3
  • P. Krakowitzky
    • 4
  • J. Fritze
    • 5
  • P. Franke
    • 6
  • B. Bandelow
    • 7
  • R. Fimmers
    • 8
  • J. Flint
    • 3
  • J. Deckert
    • 1
  1. 1.Laboratory of Molecular Psychiatry, Department of PsychiatryUniversity of MünsterMünsterGermany
  2. 2.Department of Child & Adolescent PsychiatryUniversity of SaarlandSaarlandGermany
  3. 3.Wellcome Trust Centre for Human GeneticsUniversity of OxfordOxfordUK
  4. 4.Institute of Transfusion MedicineUniversity of MünsterMünsterGermany
  5. 5.Department of PsychiatryUniversity of FrankfurtFrankfurtGermany
  6. 6.Department of PsychiatryUniversity of BonnBonnGermany
  7. 7.Department of PsychiatryUniversity of GötttingenGötttingenGermany
  8. 8.Institute for Medical Biometry, Informatics and EpidemiologyUniversity of BonnBonnGermany

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