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Dysbindin

Evidence implicating dystrobrevin-binding protein 1 (DTNBP1), also known as dysbindin, in schizophrenia was first reported by Straub et al,³⁶ and there is now quite impressive support from a number of studies reviewed recently.³⁷ However, once again various markers and haplotypes have been associated, and the actual susceptibility variants have yet to be identified. Raybould and colleagues³⁸ reported the first study of single-nucleotide polymorphisms (SNPs) from dysbindin in bipolar disorder. They found no significant associations in bipolar disorder as a whole but found modestly significant evidence for association in a subset of bipolar cases with predominantly psychotic episodes. This finding suggests that variation in dysbindin confers risk to some aspect of the psychotic syndrome rather than to the DSM-IV schizophrenia phenotype per se, although replication is required. More recently, Breen et al³⁹ reported evidence for association with dysbidin SNPs in a small sample of bipolar patients, though no analyses stratified by phenotype were conducted. Recent work in the Irish Study of High-Density Schizophrenia Families has shown that schizophrenic patients with negative symptoms were more likely to inherit the dysbindin risk haplotype,⁴⁰ raising the possibility that negative symptoms might also be part of the clinical presentation of the subgroup of psychotic bipolar cases that are particularly likely to carry the dysbindin risk haplotype.

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