Association between RGS4 variants and psychotic-like experiences in nonclinical individuals

The psychosis phenotype is expressed across a continuum known as schizotypy, which ranges from personality variation through subclinical symptoms to severe psychopathology. The study of subclinical manifestations in non-affected individuals minimizes confounding factors associated with the clinical phenotype and facilitates the differentiation of dimension-specific etiological mechanisms. The aim of the present study was to investigate the association between the variation in the regulator of G-protein signaling 4 (RGS4) gene, a putative candidate gene for psychosis previously associated with schizophrenia endophenotypes, and psychotic-like experiences (PLEs). In total, 808 healthy individuals completed the community assessment of psychic experiences (CAPE) to measure positive and negative PLEs and provided a DNA sample. Two RGS4 single-nucleotide polymorphisms (SNPs) (rs951436 [SNP4] and rs2661319 [SNP18]) were genotyped. Analyses of covariance (ANCOVA) were used to explore the association of positive and negative PLEs with RGS4 variation. Our results showed associations of positive and negative PLEs with the two polymorphisms studied: subjects with the T allele (SNP4) and the A allele (SNP18) had higher scores on both the positive and the negative dimensions. Haplotypic analyses supported these results, showing the highest scores in those with the TA haplotype (SNP4-SNP18). The RGS4 variants might exert gene-specific modulating effects on psychosis proneness.