title: Impaired metabolic reactivity to oxidative stress in early psychosis patients.
abstract: Because increasing evidence point to the convergence of environmental and genetic risk factors to drive redox dysregulation in schizophrenia, we aim to clarify whether the metabolic anomalies associated with early psychosis reflect an adaptation to oxidative stress. Metabolomic profiling was performed to characterize the response to oxidative stress in fibroblasts from control individuals (n = 20) and early psychosis patients (n = 30), and in all, 282 metabolites were identified. In addition to the expected redox/antioxidant response, oxidative stress induced a decrease of lysolipid levels in fibroblasts from healthy controls that were largely muted in fibroblasts from patients. Most notably, fibroblasts from patients showed disrupted extracellular matrix- and arginine-related metabolism after oxidative stress, indicating impairments beyond the redox system. Plasma membrane and extracellular matrix, 2 regulators of neuronal activity and plasticity, appeared as particularly susceptible to oxidative stress and thus provide novel mechanistic insights for pathophysiological understanding of early stages of psychosis. Statistically, antipsychotic medication at the time of biopsy was not accounting for these anomalies in the metabolism of patients' fibroblasts, indicating that they might be intrinsic to the disease. Although these results are preliminary and should be confirmed in a larger group of patients, they nevertheless indicate that the metabolic signature of reactivity to oxidative stress may provide reliable early markers of psychosis. Developing protective measures aimed at normalizing the disrupted pathways should prevent the pathological consequences of environmental stressors.
authors.affiliation: Department of Psychiatry, Unit for Research in Schizophrenia, Center for Psychiatric Neuroscience, Lausanne University Hospital (CHUV), Lausanne, Switzerland;
authors.forename: Margot
authors.initials: M
authors.lastname: Fournier
authors.affiliation: Department of Psychiatry, Unit for Research in Schizophrenia, Center for Psychiatric Neuroscience, Lausanne University Hospital (CHUV), Lausanne, Switzerland;Department of Psychiatry, Service of General Psychiatry, Lausanne University Hospital (CHUV), Lausanne, Switzerland;
authors.forename: Carina
authors.initials: C
authors.lastname: Ferrari
authors.affiliation: Department of Psychiatry, Unit for Research in Schizophrenia, Center for Psychiatric Neuroscience, Lausanne University Hospital (CHUV), Lausanne, Switzerland;Department of Psychiatry, Service of General Psychiatry, Lausanne University Hospital (CHUV), Lausanne, Switzerland;
authors.forename: Philipp S
authors.initials: PS
authors.lastname: Baumann
authors.affiliation: Department of Psychiatry, Unit for Research in Schizophrenia, Center for Psychiatric Neuroscience, Lausanne University Hospital (CHUV), Lausanne, Switzerland;Department of Psychiatry, Service of General Psychiatry, Lausanne University Hospital (CHUV), Lausanne, Switzerland;
authors.forename: Andrea
authors.initials: A
authors.lastname: Polari
authors.affiliation: Department of Psychiatry, Unit for Research in Schizophrenia, Center for Psychiatric Neuroscience, Lausanne University Hospital (CHUV), Lausanne, Switzerland;
authors.forename: Aline
authors.initials: A
authors.lastname: Monin
authors.affiliation: Department of Psychiatry, Unit for Research in Schizophrenia, Center for Psychiatric Neuroscience, Lausanne University Hospital (CHUV), Lausanne, Switzerland;
authors.forename: Tanja
authors.initials: T
authors.lastname: Bellier-Teichmann
authors.affiliation: Metabolon Inc, Durham, NC.
authors.forename: Jacob
authors.initials: J
authors.lastname: Wulff
authors.affiliation: Metabolon Inc, Durham, NC.
authors.forename: Kirk L
authors.initials: KL
authors.lastname: Pappan
authors.affiliation: Department of Psychiatry, Unit for Research in Schizophrenia, Center for Psychiatric Neuroscience, Lausanne University Hospital (CHUV), Lausanne, Switzerland;
authors.forename: Michel
authors.initials: M
authors.lastname: Cuenod
authors.affiliation: Department of Psychiatry, Service of General Psychiatry, Lausanne University Hospital (CHUV), Lausanne, Switzerland;
authors.forename: Philippe
authors.initials: P
authors.lastname: Conus
authors.affiliation: Department of Psychiatry, Unit for Research in Schizophrenia, Center for Psychiatric Neuroscience, Lausanne University Hospital (CHUV), Lausanne, Switzerland; kim.do@chuv.ch.
authors.forename: Kim Q
authors.initials: KQ
authors.lastname: Do
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology; D000328:Adult; D002462:Cell Membrane / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D055432:Metabolomics; D018384:Oxidative Stress / Q000502:physiology*; D011618:Psychotic Disorders / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
keywords: arginine; extracellular matrix; glutathione; mental disorder; metabolism; phospholipid