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

Nature Neuroscience volume 8, pages 15001502 (2005) | Download Citation

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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.

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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

Affiliations

  1. Center for Interdisciplinary Brain Sciences Research, Stanford University School of Medicine, 401 Quarry Road, Stanford, California 94305–5795, 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, CH-1206 Geneva, Switzerland.

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

    • Christine Hinard
    •  & Michael A Morris
  5. Department of Psychiatry and Behavioral Sciences, University of Washington, Box 359911, Seattle, Washington 98104, USA.

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

    • Stylianos E Antonarakis

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Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Allan L Reiss.

Supplementary information

PDF files

  1. 1.

    Supplementary Table 1

    Characteristics of Study Sample.

  2. 2.

    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

  3. 3.

    Supplementary Methods

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DOI

https://doi.org/10.1038/nn1572

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