| Abstract |
分子内异常glucocorticoid receptor (GR) stress signaling pathway may confer, or reflect, susceptibility to stress inschizophreniaand bipolar disorder, but the extent of such abnormalities in the brain is not known. Using RNA-Seq and qPCR in two postmortem cohorts totaling 55schizophrenia, 34 bipolar disorder and 55 control individuals, we identified increased FKBP5 andPTGES3mRNA expression, and decreased BAG1 mRNA expression, in the prefrontal cortex inschizophreniacases relative to controls (68.0% [p < 0.001], 26.0% [p < 0.01] and 12.1% [p < 0.05] respectively). We also observed increased FKBP5 and decreased BAG1 mRNA expression in bipolar disorder (47.5% [p < 0.05] and 14.9% [p < 0.005]). There were no diagnostic differences in steady-state FKBP51 protein levels, nor in HSPA1A, HSP90AA1, DNAJB1 or HSPB1 mRNA levels. GR, co-factor and chaperone mRNA levels were strongly correlated. These results reveal coordinated cortical dysregulation of FKBP5,PTGES3, BAG1 and GR genes within the glucocorticoid signaling pathway in psychotic illness. |