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

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Název: Redox dysregulation as a link between childhood trauma and psychopathological and neurocognitive profile in patients with early psychosis.
Autoři: 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.
Rok vydání: 2025
Sbírka: Université de Lausanne (UNIL): Serval - Serveur académique lausannois
Témata: 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, psychopathology, psychosis
Popis: 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.
Druh dokumentu: article in journal/newspaper
Popis souboru: application/pdf
Jazyk: English
ISSN: 1091-6490
Relation: Proceedings of the National Academy of Sciences; https://iris.unil.ch/handle/iris/255566; serval:BIB_F654E1FB2620; 000452124700053
DOI: 10.1073/pnas.1812821115
Dostupnost: https://iris.unil.ch/handle/iris/255566
https://doi.org/10.1073/pnas.1812821115
Přístupové číslo: edsbas.C37E2BE4
Databáze: BASE
Popis
Abstrakt: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.
ISSN:10916490
DOI:10.1073/pnas.1812821115