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.
|Journal||European Archives of Psychiatry and Clinical Neuroscience|
|Publication status||Published - 2010|