Impaired endoplasmic reticulum stress response in B-lymphoblasts from patients with bipolar-I disorder

Backgroud: Aberrant intracellular calcium (Ca2+) signaling in patients with bipolar-I disorder (BD-I) suggests disturbed endoplasmic reticulum (ER) function in BD. We examined whether the ER stress response is altered in BD-I patients and the relationship to basal intracellular Ca2+ levels ([Ca2+](B)), in B lymphoblasts (BLCLs) from BD-I patients. Methods: Endoplasmic reticulum stress-induced X-box binding protein I (XBPI), C/EBP homologous protein (CHOP), and GRP78 expression in BLCLs from BD-1 subjects stratified on elevated or normal [Ca2+](B) and control subjects were determined by real-time quantitative reverse transcription polymerase chain reaction. The XBP1 - 116C/G polymorphism, which impairs the XBP1 loop in the ER stress response, were genotyped with a TaqMan-based assay. Results: Compared with control subjects, thapsigargin- and tunicamycin- induced increases in XBP1 and CHOP but not GRP78 messenger RNA levels were significantly lower in BD-I patients. However, induction of these genes did not differ significantly in the two BD-I subgroups stratified on [Ca2+](B). Furthermore, the attenuated XBP1 induction cannot be explained solely by differences of XBP1 - 116C/G genotype frequency. Conclusions: Our findings suggest that the ER stress response is impaired in BD-1 patients but irrespective of altered intracellular Ca2+ homeostasis as reflected in elevated (Ca2+](B). Moreover, an effect of XBP1 - 116C/G polymorphism could not account for the attenuated XBP1 induction in bipolar-I disorder observed in this study.