title: Decreased glutathione levels predict loss of brain volume in children and adolescents with first-episode psychosis in a two-year longitudinal study.
abstract: Progressive loss of cortical gray matter (GM), as measured by magnetic resonance imaging, has been described early in the course of first-episode psychosis. This study aims to assess the relationship between oxidative balance and progression of cortical GM changes in a multicenter sample of first-episode early-onset psychosis (EOP) patients from baseline to two-year follow-up. A total of 48 patients (13 females, mean age 15.9±1.5 years) and 56 age- and gender-matched healthy controls (19 females, 15.3±1.5 years) were assessed. Magnetic resonance imaging (MRI) scans performed both at the time of the first psychotic episode and 2 years later were used for volumetric measurements of left and right gray matter regions (frontal, parietal, and temporal lobes) and total sulcal cerebrospinal fluid (CSF). Total glutathione (GSH) blood levels were determined at baseline. In patients, after controlling for possible confounding variables, lower baseline GSH levels were significantly associated with greater volume decrease in left frontal (B=0.034, 95% confidence interval (CI): 0.011 to 0.056, r=0.620, p=0.006), parietal (B=0.039, 95% CI: 0.020 to 0.059, r=0.739, p=0.001), temporal (B=0.026, 95% CI: 0.016 to 0.036, r=0.779, p<0.001), and total (B=0.022, 95% CI: 0.014 to 0.031, r=0.803, p<0.001) gray matter, and with greater increase in total CSF (B=-0.560, 95% CI: -0.270 to -0.850, r=-0.722, p=0.001). Controls did not show significant associations between brain volume changes and GSH levels. GSH deficit during the first psychotic episode was related to greater loss of cortical GM two years later in patients with first-episode EOP, suggesting that oxidative damage may contribute to the progressive loss of cortical GM found in patients with first-episode psychosis.
authors.affiliation: Department of Child and Adolescent Psychiatry, Hospital General Universitario Gregorio Marañón, Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Madrid, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Fraguas
authors.forename: Ana
authors.initials: A
authors.lastname: Gonzalez-Pinto
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Micó
authors.forename: Santiago
authors.initials: S
authors.lastname: Reig
authors.forename: Mara
authors.initials: M
authors.lastname: Parellada
authors.forename: Mónica
authors.initials: M
authors.lastname: Martínez-Cengotitabengoa
authors.forename: Josefina
authors.initials: J
authors.lastname: Castro-Fornieles
authors.forename: Marta
authors.initials: M
authors.lastname: Rapado-Castro
authors.forename: Immaculada
authors.initials: I
authors.lastname: Baeza
authors.forename: Joost
authors.initials: J
authors.lastname: Janssen
authors.forename: Manuel
authors.initials: M
authors.lastname: Desco
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Leza
authors.forename: Celso
authors.initials: C
authors.lastname: Arango
mesh_terms: D000293:Adolescent; D000704:Analysis of Variance; D001921:Brain / Q000473:pathology*; D016022:Case-Control Studies; D002648:Child; D005260:Female; D005978:Glutathione / Q000097:blood*; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D018384:Oxidative Stress / Q000502:physiology; D011237:Predictive Value of Tests; D011618:Psychotic Disorders / Q000097:blood* / Q000473:pathology* / Q000503:physiopathology; D012044:Regression Analysis
chemical_list: D005978:Glutathione