DAOA/G72 predicts the progression of prodromal syndromes to first episode psychosis

R. Mossner, A. Schuhmacher, M. Wagner, B.B. Quednow, I. Frommann, K. Kuhn, Sibylle Schwab, M. Rietschel, P. Falkai, W. Wolwer, S. Ruhrmann, A. Bechdolf, W. Gaebel, J. Klosterkotter, W. Maier

    Research output: Contribution to journalArticle

    29 Citations (Scopus)

    Abstract

    The genetic factors determining the progressionof prodromal syndromes to first episode schizophrenia haveremained enigmatic to date. In a unique prospective multicentretrial, we assessed whether variants at the D-aminoacid oxidase activator (DAOA)/G72 locus influence progressionto psychosis. Young subjects with a prodromalsyndrome were observed prospectively for up to 2 years toassess the incidence of progression to schizophrenia or firstepisode psychosis. Of the 82 probands with a prodromalsyndrome, 21 probands experienced progression to psychosiswithin the observation period. Assessment of ninecommon variants in the DAOA/G72 locus yielded twovariants with the predictive value for symptom progression:all four probands with the rs1341402 CC genotypedeveloped psychosis compared with 17 out of 78 probandswith the TT or CT genotypes (v2 = 12.348; df = 2;p = 0.002). The relative risk for progression to psychosiswas significantly increased in the CC genotype:RR = 4.588 (95% CI = 2.175–4.588). Similarly, forrs778294, 50% of probands with the AA genotype, but only22% of probands with a GG or GA genotype progressed topsychosis (v2 = 7.027; df = 2; p = 0.030). Moreover,haplotype analysis revealed a susceptibility haplotype forprogression to psychosis. This is one of the first studies toidentify a specific genetic factor for the progression ofprodromal syndromes to schizophrenia, and furtherunderscores the importance of the DAOA/G72 gene forschizophrenia.
    Original languageEnglish
    Pages (from-to)209-215
    JournalEuropean Archives of Psychiatry and Clinical Neuroscience
    Volume260
    Issue number3
    DOIs
    Publication statusPublished - 2010

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