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Have schizophrenia genes been found?

Purpose of review The understanding of the molecular genetics of schizophrenia has advanced considerably in recent years. New findings are scrutinized, particularly concentrating on progress since mid-2002. Recent findings Recent studies have focused on positional and functional candidate genes postulated to be associated with schizophrenia. These include neuregulin, dysbindin, G72/D-amino acid oxidase, proline dehydrogenase (PRODH), catechol-O-methyltransferase (COMT), regulator of G protein signalling (RGS-4), 5HT2A and dopamine D3 receptor. There is also a promising newcomer, PPP3CC. Three new studies support the role of neuregulin. Similarly, associations with dysbindin are present in all samples reported to date, although with different haplotypes. As yet, there is one study implicating G72 and this has also just been implicated with bipolar affective disorder. COMT and PRODH are both genes located within the linkage/Velo-Cardio Facial Syndrome (VCFS) microdeletion region of chromosome 22q. COMT seems likely to play an etiological role in schizophrenia although whether a high or low-activity variant is responsible is currently unclear. The evidence for PRODH is equivocal, with several positive studies but one larger negative one. RGS-4 has also received recent support and a metaanalysis continues to support an association between schizophrenia and the functional candidate genes, 5HT2A and dopamine D3 receptor. Summary Schizophrenia genes have been found at last. A potentially exciting phase of research is imminent. It is likely that more susceptibility genes and the functional significance of variations within them will be identified. Potentially, this has implications for future treatments. We also suggest that, in light of further genetic evidence, a re-evaluation of psychiatric classification may be required.