{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:23:58Z","timestamp":1785803038952,"version":"3.56.0"},"reference-count":65,"publisher":"Wiley","license":[{"start":{"date-parts":[[2022,12,6]],"date-time":"2022-12-06T00:00:00Z","timestamp":1670284800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Umecrine Cognition AB"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Canadian Journal of Gastroenterology and Hepatology"],"published-print":{"date-parts":[[2022,12,6]]},"abstract":"<jats:p>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\u2009=\u20090.03\u2009ng\/ml (IQR\u2009=\u20090.025)) and PBC patients (0.031 (0.42), <jats:inline-formula>\n                     <a:math xmlns:a=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\">\n                        <a:mi>p<\/a:mi>\n                        <a:mo>=<\/a:mo>\n                        <a:mn>0.42<\/a:mn>\n                     <\/a:math>\n                  <\/jats:inline-formula>). Within the PBC cohort, higher allopregnanolone levels were observed in younger patients (r (120)\u2009=\u2009\u22120.53, <jats:inline-formula>\n                     <c:math xmlns:c=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M2\">\n                        <c:mi>p<\/c:mi>\n                        <c:mo>&lt;<\/c:mo>\n                        <c:mn>0.001<\/c:mn>\n                     <\/c:math>\n                  <\/jats:inline-formula>) but not healthy controls (r (39)\u2009=\u2009\u22120.21, <jats:inline-formula>\n                     <e:math xmlns:e=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M3\">\n                        <e:mi>p<\/e:mi>\n                        <e:mo>=<\/e:mo>\n                        <e:mn>0.21<\/e:mn>\n                     <\/e:math>\n                  <\/jats:inline-formula>). Allopregnanolone levels were elevated in the PBC-40 domains, cognition (u\u2009=\u20091034, <jats:inline-formula>\n                     <g:math xmlns:g=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M4\">\n                        <g:mi>p<\/g:mi>\n                        <g:mo>=<\/g:mo>\n                        <g:mn>0.02<\/g:mn>\n                     <\/g:math>\n                  <\/jats:inline-formula>), emotional (u\u2009=\u20091374, <jats:inline-formula>\n                     <i:math xmlns:i=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M5\">\n                        <i:mi>p<\/i:mi>\n                        <i:mo>=<\/i:mo>\n                        <i:mn>0.004<\/i:mn>\n                     <\/i:math>\n                  <\/jats:inline-formula>), and itch (u\u2009=\u2009795, <jats:inline-formula>\n                     <k:math xmlns:k=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M6\">\n                        <k:mi>p<\/k:mi>\n                        <k:mo>=<\/k:mo>\n                        <k:mn>0.03<\/k:mn>\n                     <\/k:math>\n                  <\/jats:inline-formula>). Severe cognitive symptoms associated with a younger age: severe (50 (12)) vs. none (60 (13); u\u2009=\u2009423 <jats:inline-formula>\n                     <m:math xmlns:m=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M7\">\n                        <m:mi>p<\/m:mi>\n                        <m:mo>=<\/m:mo>\n                        <m:mn>0.001<\/m:mn>\n                     <\/m:math>\n                  <\/jats:inline-formula>). 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.<\/jats:p>","DOI":"10.1155\/2022\/3618090","type":"journal-article","created":{"date-parts":[[2022,12,6]],"date-time":"2022-12-06T19:36:01Z","timestamp":1670355361000},"page":"1-13","source":"Crossref","is-referenced-by-count":13,"title":["Neurosteroid Activation of GABA-A Receptors: A Potential Treatment Target for Symptoms in Primary Biliary Cholangitis?"],"prefix":"10.1155","volume":"2022","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4989-9726","authenticated-orcid":true,"given":"Aaron","family":"Wetten","sequence":"first","affiliation":[{"name":"Translational and Clinical Research Institute, Newcastle University, Newcastle-upon-Tyne, UK"},{"name":"Freeman Hospital, Newcastle-upon-Tyne, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Ogle","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute, Newcastle University, Newcastle-upon-Tyne, UK"},{"name":"Freeman Hospital, Newcastle-upon-Tyne, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Mells","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinod S.","family":"Hegade","sequence":"additional","affiliation":[{"name":"Leeds Liver Unit, St James\u2019 University Hospital, Leeds, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Jopson","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute, Newcastle University, Newcastle-upon-Tyne, UK"},{"name":"Freeman Hospital, Newcastle-upon-Tyne, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret","family":"Corrigan","sequence":"additional","affiliation":[{"name":"Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Palmer","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute, Newcastle University, Newcastle-upon-Tyne, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maja","family":"Johansson","sequence":"additional","affiliation":[{"name":"Umecrine Cognition AB, Solna, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torbj\u00f6rn","family":"B\u00e4ckstr\u00f6m","sequence":"additional","affiliation":[{"name":"Umecrine Cognition AB, Solna, Sweden"},{"name":"Department of Clinical Sciences, Obstetrics and Gynecology, Ume\u00e5 University, Umea, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magnus","family":"Doverskog","sequence":"additional","affiliation":[{"name":"Umecrine Cognition AB, Solna, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David E. J.","family":"Jones","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute, Newcastle University, Newcastle-upon-Tyne, UK"},{"name":"Freeman Hospital, Newcastle-upon-Tyne, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica K.","family":"Dyson","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute, Newcastle University, Newcastle-upon-Tyne, UK"},{"name":"Freeman Hospital, Newcastle-upon-Tyne, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(15)00154-3"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22371"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26365"},{"key":"4","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2005.065862"},{"key":"5","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-020-06502-0"},{"key":"6","doi-asserted-by":"publisher","DOI":"10.1111\/liv.12560"},{"key":"7","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2010.05.026"},{"key":"8","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2020.06.025"},{"key":"9","doi-asserted-by":"publisher","DOI":"10.1111\/apt.13794"},{"key":"10","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2010.02.022"},{"key":"11","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21230"},{"key":"12","doi-asserted-by":"publisher","DOI":"10.1111\/liv.12026"},{"key":"13","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v10.i20.3039"},{"key":"14","doi-asserted-by":"publisher","DOI":"10.1016\/s0168-8278(05)80640-3"},{"key":"15","doi-asserted-by":"publisher","DOI":"10.1111\/j.1478-3231.2005.01214.x"},{"key":"16","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21609"},{"key":"17","doi-asserted-by":"publisher","DOI":"10.1097\/01.meg.0000252629.96043.67"},{"key":"18","doi-asserted-by":"publisher","DOI":"10.1177\/1051228405282242"},{"key":"19","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2003.016766"},{"key":"20","doi-asserted-by":"publisher","DOI":"10.1111\/apt.13797"},{"key":"21","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2013.04.017"},{"key":"22","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2010.05.036"},{"key":"23","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2013.02.019"},{"key":"24","doi-asserted-by":"publisher","DOI":"10.1016\/s0306-4530(02)00064-1"},{"key":"25","doi-asserted-by":"publisher","DOI":"10.1016\/s0006-8993(02)02414-9"},{"key":"26","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-008-1150-7"},{"key":"27","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-018-4864-1"},{"key":"28","doi-asserted-by":"publisher","DOI":"10.1016\/s0306-4530(03)00026-x"},{"key":"29","doi-asserted-by":"publisher","DOI":"10.1016\/j.ynstr.2019.100198"},{"key":"30","doi-asserted-by":"publisher","DOI":"10.1007\/s11920-015-0627-4"},{"key":"31","doi-asserted-by":"publisher","DOI":"10.1023\/a:1021949616422"},{"key":"32","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2006.02.002"},{"key":"33","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20534"},{"key":"34","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2982.2007.01080.x"},{"key":"35","doi-asserted-by":"publisher","DOI":"10.1159\/000440757"},{"key":"36","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2002.32993"},{"key":"37","doi-asserted-by":"publisher","DOI":"10.1002\/hep.30099"},{"key":"38","doi-asserted-by":"publisher","DOI":"10.1080\/14656566.2021.1940135"},{"key":"39","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2017-315259"},{"key":"40","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2018.07.020"},{"key":"41","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2011.06.006"},{"key":"42","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2019.09.050"},{"issue":"2","key":"43","first-page":"250","article-title":"Cognitive assessment in primary biliary cirrhosis: a case-control study","volume":"90","author":"A. Floreani","year":"1995","journal-title":"American Journal of Gastroenterology"},{"key":"44","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2012.12.005"},{"key":"45","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.83.6.4905"},{"key":"46","doi-asserted-by":"publisher","DOI":"10.1136\/gut.46.1.121"},{"key":"47","doi-asserted-by":"publisher","DOI":"10.1136\/gut.49.2.276"},{"key":"48","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-013-2942-0"},{"key":"49","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinph.2007.09.126"},{"key":"50","doi-asserted-by":"publisher","DOI":"10.1177\/1073858417717660"},{"key":"51","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinph.2009.08.016"},{"key":"52","doi-asserted-by":"publisher","DOI":"10.1038\/ctg.2017.34"},{"key":"53","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00073.2015"},{"key":"54","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2021.03.012"},{"key":"55","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-38858-3"},{"key":"56","doi-asserted-by":"publisher","DOI":"10.1016\/j.ynstr.2020.100215"},{"key":"57","doi-asserted-by":"publisher","DOI":"10.1007\/bf03343883"},{"key":"58","doi-asserted-by":"publisher","DOI":"10.1016\/j.yhbeh.2015.10.010"},{"key":"59","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2006.06.005"},{"key":"60","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2012.53"},{"key":"61","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(85)90642-0"},{"key":"62","doi-asserted-by":"publisher","DOI":"10.1111\/liv.13919"},{"key":"63","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2022.09.005"},{"key":"64","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2007.06.002"},{"key":"65","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2010.01059.x"}],"container-title":["Canadian Journal of Gastroenterology and Hepatology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/cjgh\/2022\/3618090.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/cjgh\/2022\/3618090.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/cjgh\/2022\/3618090.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,6]],"date-time":"2022-12-06T19:36:08Z","timestamp":1670355368000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.hindawi.com\/journals\/cjgh\/2022\/3618090\/"}},"subtitle":[],"editor":[{"given":"Alessandro","family":"Granito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,12,6]]},"references-count":65,"alternative-id":["3618090","3618090"],"URL":"https:\/\/doi.org\/10.1155\/2022\/3618090","relation":{},"ISSN":["2291-2797","2291-2789"],"issn-type":[{"value":"2291-2797","type":"electronic"},{"value":"2291-2789","type":"print"}],"subject":[],"published":{"date-parts":[[2022,12,6]]}}}