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


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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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).


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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.).

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Correspondence to Allan L Reiss.

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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)

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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).

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