Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Brief Communication
  • Published:

COMT genotype predicts longitudinal cognitive decline and psychosis in 22q11.2 deletion syndrome

Nature Neuroscience volume 8, pages 1500–1502 (2005)Cite this article

Abstract

Although schizophrenia is strongly hereditary, there are limited data regarding biological risk factors and pathophysiological processes. In this longitudinal study of adolescents with 22q11.2 deletion syndrome, we identified the catechol-O-methyltransferase low-activity allele (COMTL) as a risk factor for decline in prefrontal cortical volume and cognition, as well as for the consequent development of psychotic symptoms during adolescence. The 22q11.2 deletion syndrome is a promising model for identifying biomarkers related to the development of schizophrenia.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Box plots show the range of values for each group, as well as the 25th, 50th (dark bar) and 75th percentiles.
Figure 2: Correlation between change in VIQ and BPRS scores in subjects with 22q11.2DS (r = 0.71, P < 0.0001).

Similar content being viewed by others

References

  1. Sullivan, P.F., Kendler, K.S. & Neale, M.C. Arch. Gen. Psychiatry 60, 1187–1192 (2003).

    Article  Google Scholar 

  2. Weinberger, D.R. Lancet 346, 552–557 (1995).

    Article  CAS  Google Scholar 

  3. Murphy, K.C., Jones, L.A. & Owen, M.J. Arch. Gen. Psychiatry 56, 940–945 (1999).

    Article  CAS  Google Scholar 

  4. Karayiorgou, M. et al. Proc. Natl. Acad. Sci. USA 92, 7612–7616 (1995).

    Article  CAS  Google Scholar 

  5. Pulver, A.E. et al. J. Nerv. Ment. Dis. 182, 476–478 (1994).

    Article  CAS  Google Scholar 

  6. Maynard, T.M. et al. Proc. Natl. Acad. Sci. USA 100, 14433–14438 (2003).

    Article  CAS  Google Scholar 

  7. Shifman, S. et al. Am. J. Hum. Genet. 71, 1296–1302 (2002).

    Article  CAS  Google Scholar 

  8. Liu, H. et al. Proc. Natl. Acad. Sci. USA 99, 3717–3722 (2002).

    Article  CAS  Google Scholar 

  9. Chen, J. et al. Am. J. Hum. Genet. 75, 807–821 (2004).

    Article  CAS  Google Scholar 

  10. Bearden, C.E. et al. Am. J. Psychiatry 161, 1700–1702 (2004).

    Article  Google Scholar 

  11. Mattay, V.S. et al. Proc. Natl. Acad. Sci. USA 100, 6186–6191 (2003).

    Article  CAS  Google Scholar 

  12. Seamans, J.K. & Yang, C.R. Prog. Neurobiol. 74, 1–57 (2004).

    Article  CAS  Google Scholar 

  13. Blasi, G. et al. J. Neurosci. 25, 5038–5045 (2005).

    Article  CAS  Google Scholar 

  14. Gogos, J.A. et al. Proc. Natl. Acad. Sci. USA 95, 9991–9996 (1998).

    Article  CAS  Google Scholar 

  15. Fuller, R. et al. Am. J. Psychiatry 159, 1183–1189 (2002).

    Article  Google Scholar 

Download references

Acknowledgements

We thank L. Xiaoyan and J.F. Hallmayer for DNA extraction, and J. Keller for cognitive assessments. This work was supported by US National Institutes of Health grants MH50047, HD31715 and MH19908 (A.L.R.) and by the Swiss National Science Foundation, the European Union Federal Office of Education and the 'Child Care' Foundation (S.E.A.).

Author information

Authors and Affiliations

  1. Center for Interdisciplinary Brain Sciences Research, Stanford University School of Medicine, 401 Quarry Road, Stanford, 94305–5795, California, USA

    Doron Gothelf, Tracy Thompson, Lauren Penniman, Carl Feinstein, Shuting Jin, Booil Jo & Allan L Reiss

  2. Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel

    Doron Gothelf

  3. Department of Psychiatry, University of Geneva School of Medicine, 41 Ch. des Crêts-de-Champel, Geneva, CH-1206, Switzerland

    Stephan Eliez

  4. Medical Genetics Service, University Hospitals, 1 Rue Michel Servet, Geneva, 1211, Switzerland

    Christine Hinard & Michael A Morris

  5. Department of Psychiatry and Behavioral Sciences, University of Washington, Box 359911, Seattle, 98104, Washington, USA

    Hower Kwon

  6. Department of Genetic Medicine and Development, University Medical School, Centre Medicale Universitaire, 1 Rue Michel Servet, Geneva, 1211, Switzerland

    Stylianos E Antonarakis

Authors
  1. Doron Gothelf
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Stephan Eliez
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tracy Thompson
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Christine Hinard
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lauren Penniman
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Carl Feinstein
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hower Kwon
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Shuting Jin
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Booil Jo
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Stylianos E Antonarakis
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Michael A Morris
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Allan L Reiss
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Allan L Reiss.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Table 1

Characteristics of Study Sample. (PDF 37 kb)

Supplementary Table 2

The effect of COMT and PRODH genotypes on longitudinal change in BPRS, VIQ, CELFE scores and PFC volumes, of subjects with 22q11.2DS (PDF 55 kb)

Supplementary Methods (PDF 74 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gothelf, D., Eliez, S., Thompson, T. et al. COMT genotype predicts longitudinal cognitive decline and psychosis in 22q11.2 deletion syndrome. Nat Neurosci 8, 1500–1502 (2005). https://doi.org/10.1038/nn1572

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nn1572

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing