RESUMO
BACKGROUND: The use of symptom dimensions of schizophrenia as quantitative phenotypes has been proposed as a mean to reduce the heterogeneity of schizophrenia and facilitate genetic research. However, the genetic background of symptom dimensions is not clear. AIM: We aim to investigate whether the symptom dimensions "reality distortion", "psychomotor poverty" and "disorganization" are heritable phenotypes. METHOD: We performed a Medline search including all papers from 1980 to August 2007. In addition to reviewing the articles, we performed meta-analyses on these studies where possible. RESULTS: We identified 18 relevant papers. Only the studies on affected sibling pairs were suitable for meta-analysis. Data from twin and affected sibling studies are consistent with a genetic contribution to the disorganization dimension. However these studies did not unequivocally support a large genetic contribution to neither the reality distortion symptom dimension nor to the psychomotor poverty symptom dimension. In contrast several molecular genetic studies did report associations of genes with psychomotor poverty. CONCLUSIONS: These data suggest that only the disorganization symptom dimension may provide an useful alternative phenotype for genetic research. More research is required to make any definitive conclusions.
Assuntos
Esquizofrenia/genética , Psicologia do Esquizofrênico , Doenças em Gêmeos/diagnóstico , Doenças em Gêmeos/genética , Família , Heterogeneidade Genética , Genótipo , Humanos , Desequilíbrio de Ligação , Linhagem , Fenótipo , Transtornos Psicomotores/diagnóstico , Transtornos Psicomotores/genética , Teste de Realidade , Esquizofrenia/diagnóstico , Esquizofrenia Hebefrênica/genéticaRESUMO
We review the role of two susceptibility genes; G72 and DAAO in glutamate neurotransmission and the aetiology of schizophrenia. The gene product of G72 is an activator of DAAO (D-amino acid oxidase), which is the only enzyme oxidising D-serine. D-serine is an important co-agonist for the NMDA glutamate receptor and plays a role in neuronal migration and cell death. Studies of D-serine revealed lower serum levels in schizophrenia patients as compared to healthy controls. Furthermore, administration of D-serine as add-on medication reduced the symptoms of schizophrenia. The underlying mechanism of the involvement of G72 and DAAO in schizophrenia is probably based on decreased levels of D-serine and decreased NMDA receptor functioning in patients. The involvement of this gene is therefore indirect support for the glutamate dysfunction hypothesis in schizophrenia.
