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Comparative sequencing and association studies of aromatic L-amino acid decarboxylase in schizophrenia and bipolar disorder

Molecular Psychiatry volume 5, pages 327–331 (2000)Cite this article

Abstract

Aromatic L-amino acid decarboxylase (AADC) is a relatively non specific enzyme involved in the biosynthesis of several classical neurotransmitters including dopamine and 5-hydroxytryptamine (5HT; serotonin).1 AADC does not catalyse the rate limiting step in either pathway, but is rate limiting in the synthesis of 2-phenylethylamine (2PE) which is a positive modulator of dopaminergic transmission and a candidate natural psychotogenic compound.1 We and others have proposed that polymorphism in AADC resulting in altered 2PE activity might contribute to the pathogenesis of psychosis.1,2 In order to test this hypothesis, we have used denaturing high performance liquid chromatography (DHPLC)3 to screen 3943 bases of the aadc gene and its promoter regions for variants that might affect protein structure or expression in 15 unrelated people with schizophrenia, and 15 unrelated people with bipolar disorder. three polymorphisms were identified by dhplc: a insertion/deletion polymorphism in the 5′ utr of the neuronal specific mrna (g.-33–30delagag, bases 586–589 of genbank m77828), a t>a variant in the non-neuronal exon 1 (g.-67t>a, genbank m88070), and a g>a polymorphism within intron 8 (g.ivs8 +75g>A, GenBank M84598). Case-control analysis did not suggest that genetic polymorphism in the AADC gene is associated with liability for developing schizophrenia or bipolar disorder.

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Acknowledgements

This study was supported by a grant from the Wellcome Trust (052309) and an MRC Programme Grant (G9309834). J Austin is funded by a University of Wales College of Medicine Studentship. Ian Jones is a Wellcome Trust Research Fellow in Mental Health. Nick Craddock is a Wellcome Trust Senior Research Fellow in Clinical Sciences.

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Authors and Affiliations

  1. Division of Psychological Medicine, University of Wales College of Medicine, Heath Park, Cardiff, CF14 4XN, UK

    G Speight, D Turic, J Austin, B Hoogendoorn, A G Cardno, L Jones, K C Murphy, R Sanders, G McCarthy, M J Owen, P Buckland & M C O'Donovan

  2. Division of Neuroscience, University of Birmingham, Queen Elizabeth Psychiatric Hospital, Birmingham, B15 2QZ, UK

    I Jones, F McCandless & N Craddock

  3. Social, Genetic and Developmental Psychiatry, Institute of Psychiatry, London, SE5 8AF, UK

    P McGuffin

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  1. G Speight
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  14. M J Owen
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Correspondence to M C O'Donovan.

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Speight, G., Turic, D., Austin, J. et al. Comparative sequencing and association studies of aromatic L-amino acid decarboxylase in schizophrenia and bipolar disorder. Mol Psychiatry 5, 327–331 (2000). https://doi.org/10.1038/sj.mp.4000717

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  • DOI: https://doi.org/10.1038/sj.mp.4000717

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