{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:41:35Z","timestamp":1791232895337,"version":"4.1.0"},"reference-count":76,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T00:00:00Z","timestamp":1752537600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Polish National Ministry of Education and Science","award":["N N402 375239"],"award-info":[{"award-number":["N N402 375239"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Wilson\u2019s disease (WD) is an autosomal recessive disorder of copper metabolism caused by mutations in the ATP7B gene. While hepatic manifestations are frequent, psychiatric symptoms occur in up to 30% of patients and may precede neurological signs. This study was the first to assess the relationship between oxidative stress, selected genetic polymorphisms, and psychiatric symptoms in WD. A total of 464 patients under the care of the Institute of Psychiatry and Neurology in Warsaw were studied. Genotyping for GPX1 (rs1050450), SOD2 (rs4880), and CAT (rs1001179) was performed, along with biochemical analyses of copper metabolism, oxidative DNA, lipid and protein damage, and systemic antioxidant capacity. Among the most important observations are the following: the homozygous GPX1 rs1050450 TT and SOD2 rs4880 CC genotypes were associated with the lowest prevalence of psychiatric symptoms. The CAT rs1001179 TT genotype was linked to a delayed onset of psychiatric symptoms by 6.0\u20138.5 years. Patients with or without psychiatric symptoms did not differ significantly in saliva 8-OHdG, total antioxidant capacity, serum glutathione (GSH), catalase, and MnSOD; however, patients reporting psychiatric symptoms had significantly higher prostaglandin F2\u03b1 8-epimer (8-iso-PGF2\u03b1) concentrations and tended to have lower serum glutathione peroxidase (Gpx) concentrations compared to those without such symptoms. Our data firstly provide consistent evidence that oxidative stress balance associated with copper overload in the CNS may be associated with CNS damage and the development of psychiatric symptoms of WD. In particular, our findings of increased oxidative lipid damage together with decreased Gpx activity indirectly suggest that damage to neuronal membrane lipids, which may be potentially related to abnormalities in GSH metabolism, may have an etiological role in CNS damage and related symptoms.<\/jats:p>","DOI":"10.3390\/ijms26146774","type":"journal-article","created":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T15:01:05Z","timestamp":1752591665000},"page":"6774","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Oxidative Stress and Psychiatric Symptoms in Wilson\u2019s Disease"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4325-8971","authenticated-orcid":false,"given":"Gra\u017cyna","family":"Gromadzka","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Medicine, Collegium Medicum, Cardinal Stefan Wyszynski University, Woycickiego Street 1\/3, 01-938 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agata","family":"Karpi\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Banacha 1b Str., 02-097 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4181-3492","authenticated-orcid":false,"given":"Tomasz Krzysztof","family":"Szafra\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Faculty of Medicine, Lazarski University, Anna Gosty\u0144ska Wolski Hospital, Marcina Kasprzaka 17 Street, 01-211 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2670-9651","authenticated-orcid":false,"given":"Tomasz","family":"Litwin","sequence":"additional","affiliation":[{"name":"Department of Neurology, Stroke Unit and Rehabilitation Subunit, Anna Gostynska Wolski Hospital, Marcina Kasprzaka 17 Street, 01-211 Warsaw, Poland"},{"name":"Second Department of Neurology, Institute of Psychiatry and Neurology, Sobieskiego Street 9, 02-957 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,15]]},"reference":[{"key":"ref_1","unstructured":"Saunders, W.B. 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