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- Title
In search of susceptibility genes for schizophrenia.
- Authors
Schosser, Alexandra; Aschauer, Harald
- Abstract
After the recent discovery and replication of several schizophrenia candidate regions on multiple chromosomes, susceptibility genes for schizophrenia could be identified for the first time. Each of these discoveries resulted from association studies within chromosomal regions first identified by linkage analyses. Within the last two years, the susceptibility genes Neuregulin1, Dysbindin, D-amino-acid-oxidase ( DAAO) and G72 were discovered, which, in the variant forms, reduce glutamatergic activity in brain. Therefore, they are related to the so-called 'glutamate hypothesis', which postulates a hypofunction of the glutamatergic system. Adults with VCFS (velo-cardio-facial syndrome), where a deletion on chromosome 22q11 can be found, show a very high incidence of schizophrenia. In addition, 2% of patients with schizophrenia exhibit this 22q11 deletion. Within the VCFS-deleted region on chromosome 22q11, the genes coding for proline dehydrogenase ( PRODH) and catechol-O-methyltransferase ( COMT) were also found to be significantly associated with schizophrenia. Proline is a pre-stage of glutamate, and in addition, it seems to be a neuromodulator of glutamatergic transmission in the brain. COMT is one of the two enzymes degrading catecholamines such as dopamine. Therefore, it plays a large role in the cortical dopamine metabolism. Furthermore, an association of schizophrenia with the gene RGS4 (regulator of G protein signaling 4), a modulator of the function of multiple G-protein-linked neurotransmitter receptors, was identified. Gene expression analyses of postmortem cerebral cortex (prefrontal) indicate that the transcription of RGS4 is diminished within schizophrenics. In accordance with the fact that schizophrenia is a disease with a multifactorial etiology, it should be emphasized that the described biological risk factors can increase susceptibility, but that none of them can cause the disease alone.
- Publication
Wiener Klinische Wochenschrift, 2004, Vol 116, Issue 24, p827
- ISSN
0043-5325
- Publication type
Article
- DOI
10.1007/s00508-004-0256-0