Redox dysregulation as a link between childhood trauma and psychopathological and neurocognitive profile in patients with early psychosis.

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Version: Final published version
Serval ID
serval:BIB_F654E1FB2620
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Redox dysregulation as a link between childhood trauma and psychopathological and neurocognitive profile in patients with early psychosis.
Journal
Proceedings of the National Academy of Sciences of the United States of America
Author(s)
Alameda L., Fournier M., Khadimallah I., Griffa A., Cleusix M., Jenni R., Ferrari C., Klauser P., Baumann P.S., Cuenod M., Hagmann P., Conus P., Do K.Q.
ISSN
1091-6490 (Electronic)
ISSN-L
0027-8424
Publication state
Published
Issued date
04/12/2018
Peer-reviewed
Oui
Volume
115
Number
49
Pages
12495-12500
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Exposure to childhood trauma (CT) increases the risk for psychosis and affects the development of brain structures, possibly through oxidative stress. As oxidative stress is also linked to psychosis, it may interact with CT, leading to a more severe clinical phenotype. In 133 patients with early psychosis (EPP), we explored the relationships between CT and hippocampal, amygdala, and intracranial volume (ICV); blood antioxidant defenses [glutathione peroxidase (GPx) and thioredoxin/peroxiredoxin (Trx/Prx)]; psychopathological results; and neuropsychological results. Nonadjusted hippocampal volume correlated negatively with GPx activity in patients with CT, but not in patients without CT. In patients with CT with high GPx activity (high-GPx+CT), hippocampal volume was decreased compared with that in patients with low-GPx+CT and patients without CT, who had similar hippocampal volumes. Patients with high-GPx+CT had more severe positive and disorganized symptoms than other patients. Interestingly, Trx and oxidized Prx levels correlated negatively with GPx only in patients with low-GPx+CT. Moreover, patients with low-GPx+CT performed better than other patients on cognitive tasks. Discriminant analysis combining redox markers, hippocampal volume, clinical scores, and cognitive scores allowed for stratification of the patients into subgroups. In conclusion, traumatized EPP with high peripheral oxidation status (high-GPx activity) had smaller hippocampal volumes and more severe symptoms, while those with lower oxidation status (low-GPx activity) showed better cognition and regulation of GPx and Trx/Prx systems. These results suggest that maintained regulation of various antioxidant systems allowed for compensatory mechanisms preventing long-term neuroanatomical and clinical impacts. The redox marker profile may thus represent important biomarkers for defining treatment strategies in patients with psychosis.
Keywords
Adult, Antioxidants, Child, Female, Glutathione/metabolism, Glutathione Peroxidase/metabolism, Humans, Male, Oxidation-Reduction, Oxidative Stress, Peroxiredoxins, Psychotic Disorders/etiology, Thioredoxins, Wounds and Injuries/complications, Young Adult, childhood trauma, early psychosis, oxidative stress, psychopathology, psychosis
Pubmed
Web of science
Open Access
Yes
Create date
26/11/2018 13:40
Last modification date
20/08/2019 16:22
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