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

Journal Article


Abstract


  • The genetic factors determining the progression of prodromal syndromes to first episode schizophrenia have remained enigmatic to date. In a unique prospective multicentre trial, we assessed whether variants at the d-amino acid oxidase activator (DAOA)/G72 locus influence progression to psychosis. Young subjects with a prodromal syndrome were observed prospectively for up to 2 years to assess the incidence of progression to schizophrenia or first episode psychosis. Of the 82 probands with a prodromal syndrome, 21 probands experienced progression to psychosis within the observation period. Assessment of nine common variants in the DAOA/G72 locus yielded two variants with the predictive value for symptom progression: all four probands with the rs1341402 CC genotype developed psychosis compared with 17 out of 78 probands with the TT or CT genotypes (χ2 = 12.348; df = 2; p = 0.002). The relative risk for progression to psychosis was significantly increased in the CC genotype: RR = 4.588 (95% CI = 2.175–4.588). Similarly, for rs778294, 50% of probands with the AA genotype, but only 22% of probands with a GG or GA genotype progressed to psychosis (χ2 = 7.027; df = 2; p = 0.030). Moreover, haplotype analysis revealed a susceptibility haplotype for progression to psychosis. This is one of the first studies to identify a specific genetic factor for the progression of prodromal syndromes to schizophrenia, and further underscores the importance of the DAOA/G72 gene for schizophrenia.

UOW Authors


  •   Mossner, Rainald (external author)
  •   Schuhmacher, Anna (external author)
  •   Wagner, Michael (external author)
  •   Quednow, Boris B. (external author)
  •   Frommann, Ingo (external author)
  •   Kuhn, Kai-Uwe (external author)
  •   Schwab, Sibylle
  •   Rietschel, Marcella (external author)
  •   Falkai, Peter (external author)
  •   Wolwer, Wolfgang (external author)
  •   Ruhrmann, Stephan (external author)
  •   Bechdolf, Andreas (external author)
  •   Gaebel, Wolfgang (external author)
  •   Klosterkotter, Joachim (external author)
  •   Maier, Wolfgang (external author)

Publication Date


  • 2010

Citation


  • Mossner, R., Schuhmacher, A., Wagner, M., Quednow, B. B., Frommann, I., Kuhn, K., Schwab, S. G., Rietschel, M., Falkai, P., Wolwer, W., Ruhrmann, S., Bechdolf, A., Gaebel, W., Klosterkotter, J. & Maier, W. (2010). DAOA/G72 predicts the progression of prodromal syndromes to first episode psychosis. European Archives of Psychiatry and Clinical Neuroscience: official organ of the German society for biological psychiatry, 260 (3), 209-215.

Scopus Eid


  • 2-s2.0-77950865809

Ro Metadata Url


  • http://ro.uow.edu.au/ihmri/470

Number Of Pages


  • 6

Start Page


  • 209

End Page


  • 215

Volume


  • 260

Issue


  • 3

Abstract


  • The genetic factors determining the progression of prodromal syndromes to first episode schizophrenia have remained enigmatic to date. In a unique prospective multicentre trial, we assessed whether variants at the d-amino acid oxidase activator (DAOA)/G72 locus influence progression to psychosis. Young subjects with a prodromal syndrome were observed prospectively for up to 2 years to assess the incidence of progression to schizophrenia or first episode psychosis. Of the 82 probands with a prodromal syndrome, 21 probands experienced progression to psychosis within the observation period. Assessment of nine common variants in the DAOA/G72 locus yielded two variants with the predictive value for symptom progression: all four probands with the rs1341402 CC genotype developed psychosis compared with 17 out of 78 probands with the TT or CT genotypes (χ2 = 12.348; df = 2; p = 0.002). The relative risk for progression to psychosis was significantly increased in the CC genotype: RR = 4.588 (95% CI = 2.175–4.588). Similarly, for rs778294, 50% of probands with the AA genotype, but only 22% of probands with a GG or GA genotype progressed to psychosis (χ2 = 7.027; df = 2; p = 0.030). Moreover, haplotype analysis revealed a susceptibility haplotype for progression to psychosis. This is one of the first studies to identify a specific genetic factor for the progression of prodromal syndromes to schizophrenia, and further underscores the importance of the DAOA/G72 gene for schizophrenia.

UOW Authors


  •   Mossner, Rainald (external author)
  •   Schuhmacher, Anna (external author)
  •   Wagner, Michael (external author)
  •   Quednow, Boris B. (external author)
  •   Frommann, Ingo (external author)
  •   Kuhn, Kai-Uwe (external author)
  •   Schwab, Sibylle
  •   Rietschel, Marcella (external author)
  •   Falkai, Peter (external author)
  •   Wolwer, Wolfgang (external author)
  •   Ruhrmann, Stephan (external author)
  •   Bechdolf, Andreas (external author)
  •   Gaebel, Wolfgang (external author)
  •   Klosterkotter, Joachim (external author)
  •   Maier, Wolfgang (external author)

Publication Date


  • 2010

Citation


  • Mossner, R., Schuhmacher, A., Wagner, M., Quednow, B. B., Frommann, I., Kuhn, K., Schwab, S. G., Rietschel, M., Falkai, P., Wolwer, W., Ruhrmann, S., Bechdolf, A., Gaebel, W., Klosterkotter, J. & Maier, W. (2010). DAOA/G72 predicts the progression of prodromal syndromes to first episode psychosis. European Archives of Psychiatry and Clinical Neuroscience: official organ of the German society for biological psychiatry, 260 (3), 209-215.

Scopus Eid


  • 2-s2.0-77950865809

Ro Metadata Url


  • http://ro.uow.edu.au/ihmri/470

Number Of Pages


  • 6

Start Page


  • 209

End Page


  • 215

Volume


  • 260

Issue


  • 3