GABRB2 in schizophrenia and bipolar disorder: Disease association, gene expression and clinical correlations.

摘要

The schizophrenia- (SCZ-) associated GABAA receptor beta 2 subunit gene GABRB2 was recently reported with bipolar disorder (BPD) association in US Caucasians. The present study examined the functional mechanism of GABRB2 in the two major psychotic disorders. Association of GABRB2 with both SCZ and BPD was compared; GABRB2 expression was quantified in post-mortem brains; and clinical parameters were analyzed for genotypic correlations. Although weaker than its association with SCZ, significant association of GABRB2 with BPD was found in both German and Chinese, especially for the haplotypes rs1816071-rs187269 and rs1816072-rs187269 for which the M-M variants showed higher frequency in disease than control. Significant reduction in GABRB2 expression was shown for BPD in a genotype-dependent manner, but to a lesser extent than that reported for SCZ. Temporal effects on GABRB2 expression were observed. Moreover, for the homozygous major genotypes of rs1816071, rs1816072 and rs187269, expression increased with time in CON but decreased in SCZ and BPD. The genotypes of these three SNPs were further correlated with antipsychotics dosage in SCZ cohorts. The results highlight the importance of GABRB2 in disease etiology, with respect to haplotype association, as well as reduction of and temporal effects on gene expression in both SCZ and BPD, but to a lesser extent in the latter, supporting the suggestion that functional psychosis can be conceptualized as a continuous spectrum of clinical phenotypes rather than as distinct categories.