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D-Amino acid oxidase activity and expression are increased in schizophrenia

Molecular Psychiatry volume 13, pages 658–660 (2008)Cite this article

D-amino acid oxidase (DAO or DAAO) metabolizes the N-methyl D-aspartate receptor (NMDAR) modulator D-serine.1 Enhanced DAO activity is, thus, a potential cause of reduced D-serine and thence NMDAR functioning in schizophrenia,2 and an explanation for the genetic contribution that DAO may make to the disorder.3, 4 Here, we report that DAO activity, and expression, are increased in the cerebellum in schizophrenia, but not in bipolar disorder, and are not related to single nucleotide polymorphisms (SNPs) in DAO or its putative activator gene G72/G30.3

We measured DAO enzyme activity, and DAO mRNA by qRT-PCR (quantitative reverse transcription-PCR), using established methods, in cerebellar tissue from subjects with schizophrenia, bipolar disorder and controls, from the Stanley Microarray Collection (Supplementary Table 1). We genotyped subjects for two schizophrenia-associated tag SNPs in DAO and G72/G30. We used cerebellar tissue from rats administered haloperidol or clozapine for 14 days to investigate antipsychotic effects on DAO activity. For demographic and methodological details, see Supplementary Materials.

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Authors and Affiliations

  1. Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK

    P W J Burnet, S L Eastwood, G C Bristow, B R Godlewska, P Sikka, M Walker & P J Harrison

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  1. P W J Burnet
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  2. S L Eastwood
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  3. G C Bristow
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  4. B R Godlewska
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  5. P Sikka
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  6. M Walker
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  7. P J Harrison
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Correspondence to P J Harrison.

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Burnet, P., Eastwood, S., Bristow, G. et al. D-Amino acid oxidase activity and expression are increased in schizophrenia. Mol Psychiatry 13, 658–660 (2008). https://doi.org/10.1038/mp.2008.47

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