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Neurosteroid activa...
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Wetten, AaronTranslational and Clinical Research Institute, Newcastle University, Newcastle-upon-Tyne, United Kingdom; Freeman Hospital, Newcastle-upon-Tyne, United Kingdom
(author)
Neurosteroid activation of gaba-a receptors : a potential treatment target for symptoms in primary biliary cholangitis?
- Article/chapterEnglish2022
Publisher, publication year, extent ...
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Hindawi Publishing Corporation,2022
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electronicrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:umu-202002
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https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-202002URI
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https://doi.org/10.1155/2022/3618090DOI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
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Background and Aims: A third of patients with primary biliary cholangitis (PBC) experience poorly understood cognitive symptoms, with a significant impact on quality of life (QOL), and no effective medical treatment. Allopregnanolone, a neurosteroid, is a positive allosteric modulator of gamma-aminobutyricacid-A (GABA-A) receptors, associated with disordered mood, cognition, and memory. This study explored associations between allopregnanolone and a disease-specific QOL scoring system (PBC-40) in PBC patients.Method: Serum allopregnanolone levels were measured in 120 phenotyped PBC patients and 40 age and gender-matched healthy controls. PBC subjects completed the PBC-40 at recruitment. Serum allopregnanolone levels were compared across PBC-40 domains for those with none/mild symptoms versus severe symptoms.Results: There were no overall differences in allopregnanolone levels between healthy controls (median = 0.03 ng/ml (IQR = 0.025)) and PBC patients (0.031 (0.42), p = 0.42). Within the PBC cohort, higher allopregnanolone levels were observed in younger patients (r (120) = -0.53, p < 0.001) but not healthy controls (r (39) = -0.21, p = 0.21). Allopregnanolone levels were elevated in the PBC-40 domains, cognition (u = 1034, p = 0.02), emotional (u = 1374, p = 0.004), and itch (u = 795, p = 0.03). Severe cognitive symptoms associated with a younger age: severe (50 (12)) vs. none (60 (13); u = 423 p = 0.001).Conclusion: Elevated serum allopregnanolone is associated with severe cognitive, emotional, and itch symptoms in PBC, in keeping with its known action on GABA-A receptors. Existing novel compounds targeting allopregnanolone could offer new therapies in severely symptomatic PBC, satisfying a significant unmet need.
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Ogle, LauraTranslational and Clinical Research Institute, Newcastle University, Newcastle-upon-Tyne, United Kingdom; Freeman Hospital, Newcastle-upon-Tyne, United Kingdom
(author)
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Mells, GeorgeDepartment of Human Genetics, University of Cambridge, Cambridge, United Kingdom
(author)
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Hegade, Vinod S.Leeds Liver Unit, St James' University Hospital, Leeds, United Kingdom
(author)
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Jopson, LauraTranslational and Clinical Research Institute, Newcastle University, Newcastle-upon-Tyne, United Kingdom; Freeman Hospital, Newcastle-upon-Tyne, United Kingdom
(author)
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Corrigan, MargaretLiverpool University Hospitals NHS Foundation Trust, Liverpool, United Kingdom
(author)
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Palmer, JeremyTranslational and Clinical Research Institute, Newcastle University, Newcastle-upon-Tyne, United Kingdom
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Johansson, MajaUmecrine Cognition AB, Solna, Sweden
(author)
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Bäckström, TorbjörnUmeå universitet,Obstetrik och gynekologi,Umecrine Cognition AB, Solna, Sweden(Swepub:umu)toba0001
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Doverskog, MagnusUmecrine Cognition AB, Solna, Sweden
(author)
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Jones, David E. J.Translational and Clinical Research Institute, Newcastle University, Newcastle-upon-Tyne, United Kingdom; Freeman Hospital, Newcastle-upon-Tyne, United Kingdom
(author)
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Dyson, Jessica K.Translational and Clinical Research Institute, Newcastle University, Newcastle-upon-Tyne, United Kingdom; Freeman Hospital, Newcastle-upon-Tyne, United Kingdom
(author)
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Translational and Clinical Research Institute, Newcastle University, Newcastle-upon-Tyne, United Kingdom; Freeman Hospital, Newcastle-upon-Tyne, United KingdomDepartment of Human Genetics, University of Cambridge, Cambridge, United Kingdom
(creator_code:org_t)
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In:Canadian journal of gastroenterology & hepatology: Hindawi Publishing Corporation20222291-27892291-2797
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Wetten, Aaron
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Ogle, Laura
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Mells, George
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Hegade, Vinod S.
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Palmer, Jeremy
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Johansson, Maja
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Umeå University