Endoplasmic reticulum stress in bipolar disorder? - BiP and CHOP gene expression- and XBP1 splicing analysis in peripheral blood.
BACKGROUND
Endoplasmic Reticulum stress activates the Unfolded Protein Response, which is partially impaired in Bipolar Disorder (BD) according to previous in-vitro studies. Thus, BiP and CHOP gene expression and XBP1 splicing were analyzed in peripheral blood of study participants with BD and controls.


METHODS
RNA was isolated from fasting blood of study participants with BD (n = 81) and controls (n = 54) and reverse transcribed into cDNA. BiP and CHOP gene expression was analyzed with quantitative RT-PCR. Atypical splicing of XBP1 mRNA was measured by semi-quantitative RT-PCR, gel-electrophoresis and densitometry. ANCOVAs with the covariates age, BMI, sex, lithium and anticonvulsants intake were used with SPSS. Bonferroni correction was used to correct for multiple testing (adjusted p = 0.0083).


RESULTS
BiP gene expression was significantly higher in BD than in controls (F(1/128) = 10.076, p = 0.002, Partial η2 = 0.073). Total XBP1 (F(1/126) = 9.550, p = 0.002, Partial η2 = 0.070) and unspliced XBP1 (F(1/128)= 8.803, p= 0.004, Patial η2 = 0.065) were significantly decreased in BD. Spliced XBP1 (F(1/126) = 5.848, p = 0.017, Partial η2 = 0.044) and the ratio spliced XBP1/ unspliced XBP1 did not differ between BD and controls (F(1/126) = 0.599, p = 0.441, Partial η2 = 0.005). Gene expression did not differ between euthymia, depression and mania.


DISCUSSION
BiP gene expression was significantly higher in BD compared to controls. Total and unspliced XBP1 were significantly lower in BD than in the control group. Thus, both genes may be considered as putative trait markers. Nevertheless, XBP1 splicing itself did not differ between both groups.
['Bengesser|Susanne A|SA|', 'Reininghaus|Eva Z|EZ|', 'Dalkner|Nina|N|', 'Birner|Armin|A|', 'Hohenberger|Helena|H|', 'Queissner|Robert|R|', 'Fellendorf|Frederike|F|', 'Platzer|Martina|M|', 'Pilz|Rene|R|', 'Hamm|Carlo|C|', 'Rieger|Alexandra|A|', 'Kapfhammer|Hans-Peter|HP|', 'Mangge|Harald|H|', 'Reininghaus|Bernd|B|', 'Meier-Allard|Nathalie|N|', 'Stracke|Anika|A|', 'Fuchs|Robert|R|', 'Holasek|Sandra|S|']
D000293:Adolescent D000328:Adult D000368:Aged D000369:Aged, 80 and over D017398:Alternative Splicing D001714:Bipolar Disorder D016022:Case-Control Studies D004721:Endoplasmic Reticulum D000091342:Endoplasmic Reticulum Chaperone BiP D059865:Endoplasmic Reticulum Stress D005260:Female D006360:Heat-Shock Proteins D006801:Humans D008297:Male D008875:Middle Aged D012333:RNA, Messenger D051742:Transcription Factor CHOP D014157:Transcription Factors D059467:Transcriptome D056811:Unfolded Protein Response D000071717:X-Box Binding Protein 1
Endoplasmic Reticulum Bipolar Disorder BiP CHOP XBP1 Unfolded Protein Response ER stress GRP78