Browse by author
Lookup NU author(s): Dr Aaron Wetten, Dr Laura Ogle, Dr George Mells, Dr Vinod Hegade, Dr Laura Jopson, Dr Jeremy Palmer, Professor David Jones, Dr Jess Dyson
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2022 Aaron Wetten et al. 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.
Author(s): Wetten A, Ogle L, Mells G, Hegade VS, Jopson L, Corrigan M, Palmer J, Johansson M, Backstrom T, Doverskog M, Jones DEJ, Dyson JK
Publication type: Article
Publication status: Published
Journal: Canadian Journal of Gastroenterology and Hepatology
Year: 2022
Volume: 2022
Online publication date: 06/12/2022
Acceptance date: 09/11/2022
Date deposited: 18/09/2024
ISSN (print): 2291-2789
ISSN (electronic): 2291-2797
Publisher: Hindawi Limited
URL: https://doi.org/10.1155/2022/3618090
DOI: 10.1155/2022/3618090
Data Access Statement: All presented data are available upon request, pending approval of proposed use and signed data access agreement. Application for access to data to be made via the corresponding author.
PubMed id: 36523650
Altmetrics provided by Altmetric
