Schizophrenia (MIM 181500; http://www. ncbi. nlm. nih. gov/Omim/) is a common psychiatric disorder with a lifetime prevalence of $1%, which presents with psychotic symptoms (delusions and hallucinations), thought disorder, and deficit features described as ‘‘negative’’symptoms. Schizophrenia is a highly heritable disorder of complex genetic aetiology. Identifying susceptibility genes for complex disorders has proved difficult but a recent meta-analysis of linkage data supports a number of schizophrenia susceptibility loci [Levinson et al., 2002]. More recently, a series of studies have reported association between candidate genes and schizophrenia [reviewed by Harrison and Owen, 2003]. Several of these findings have now been replicated in independent samples including regulator of G-protein signalling 4 (RGS4) on chromosome 1q21-q22, dysbindin (DTNBP1) on 6p22. 3, neuregulin 1 (NRG1) on 8p21-p22, D-aminoacid oxidase (DAAO) on 12q24, the G72 gene on 13q34, proline dehydrogenase (PRODH) on 22q11, and catechol-O-methyltransferase (COMT) on 22q11. These, and other genes, may provide substantial insight into the pathophysiology of schizophrenia. However, in most cases, much work is still required to confirm and elucidate their contribution to the expression of the illness.

The goal of the present study is to investigate the association reported between RGS4 and schizophrenia [Chowdari et al., 2002]. These investigators [Mirnics et al., 2001] previously reported a gene expression study of schizophrenia. They investigated the expression patterns of 7,800 genes and expressed sequence tags in prefrontal cortex in six matched pairs of schizophrenia and control subjects. This identified RGS4 as significantly under-expressed in the pre-frontal cortex of schizophrenia subjects. RGS4 maps to chromosome 1q21-q22, a region linked to schizophrenia [Brzustowicz et al., 2000]. Of 70 genes on the microarray that mapped to 1q21-q22, RGS4 was the only one to demonstrate altered expression across multiple schizophrenia subjects.