title: Impaired fornix-hippocampus integrity is linked to peripheral glutathione peroxidase in early psychosis.
abstract: Several lines of evidence implicate the fornix-hippocampus circuit in schizophrenia. In early-phase psychosis, this circuit has not been extensively investigated and the underlying mechanisms affecting the circuit are unknown. The hippocampus and fornix are vulnerable to oxidative stress at peripuberty in a glutathione (GSH)-deficient animal model. The purposes of the current study were to assess the integrity of the fornix-hippocampus circuit in early-psychosis patients (EP), and to study its relationship with peripheral redox markers. Diffusion spectrum imaging and T1-weighted magnetic resonance imaging (MRI) were used to assess the fornix and hippocampus in 42 EP patients compared with 42 gender- and age-matched healthy controls. Generalized fractional anisotropy (gFA) and volumetric properties were used to measure fornix and hippocampal integrity, respectively. Correlation analysis was used to quantify the relationship of gFA in the fornix and hippocampal volume, with blood GSH levels and glutathione peroxidase (GPx) activity. Patients compared with controls exhibited lower gFA in the fornix as well as smaller volume in the hippocampus. In EP, but not in controls, smaller hippocampal volume was associated with high GPx activity. Disruption of the fornix-hippocampus circuit is already present in the early stages of psychosis. Higher blood GPx activity is associated with smaller hippocampal volume, which may support a role of oxidative stress in disease mechanisms.
authors.affiliation: Department of Psychiatry, Unit for Research in Schizophrenia, Center for Psychiatric Neuroscience, Centre Hospitalier Universitaire Vaudois, Lausanne University Hospital (CHUV), University of Lausanne, Lausanne, Switzerland.|Department of Psychiatry, Service of General Psychiatry, Centre Hospitalier Universitaire Vaudois, Lausanne University Hospital (CHUV), Lausanne, Switzerland.
authors.forename: P S
authors.initials: PS
authors.lastname: Baumann
authors.affiliation: Signal Processing Laboratory (LTS5), Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.|Department of Radiology, Lausanne University Hospital (CHUV), University of Lausanne, Lausanne, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Griffa
authors.affiliation: Department of Psychiatry, Unit for Research in Schizophrenia, Center for Psychiatric Neuroscience, Centre Hospitalier Universitaire Vaudois, Lausanne University Hospital (CHUV), University of Lausanne, Lausanne, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Fournier
authors.affiliation: Department of Psychiatry, Service of General Psychiatry, Centre Hospitalier Universitaire Vaudois, Lausanne University Hospital (CHUV), Lausanne, Switzerland.|Service of Community Psychiatry, Department of Psychiatry, Lausanne University Hospital (CHUV), Lausanne, Switzerland.
authors.forename: P
authors.initials: P
authors.lastname: Golay
authors.affiliation: Department of Psychiatry, Unit for Research in Schizophrenia, Center for Psychiatric Neuroscience, Centre Hospitalier Universitaire Vaudois, Lausanne University Hospital (CHUV), University of Lausanne, Lausanne, Switzerland.
authors.forename: C
authors.initials: C
authors.lastname: Ferrari
authors.affiliation: Department of Psychiatry, Unit for Research in Schizophrenia, Center for Psychiatric Neuroscience, Centre Hospitalier Universitaire Vaudois, Lausanne University Hospital (CHUV), University of Lausanne, Lausanne, Switzerland.|Department of Psychiatry, Service of General Psychiatry, Centre Hospitalier Universitaire Vaudois, Lausanne University Hospital (CHUV), Lausanne, Switzerland.
authors.forename: L
authors.initials: L
authors.lastname: Alameda
authors.affiliation: Department of Psychiatry, Unit for Research in Schizophrenia, Center for Psychiatric Neuroscience, Centre Hospitalier Universitaire Vaudois, Lausanne University Hospital (CHUV), University of Lausanne, Lausanne, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Cuenod
authors.affiliation: Signal Processing Laboratory (LTS5), Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.|Department of Radiology, Lausanne University Hospital (CHUV), University of Lausanne, Lausanne, Switzerland.
authors.forename: J-P
authors.initials: JP
authors.lastname: Thiran
authors.affiliation: Signal Processing Laboratory (LTS5), Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.|Department of Radiology, Lausanne University Hospital (CHUV), University of Lausanne, Lausanne, Switzerland.
authors.forename: P
authors.initials: P
authors.lastname: Hagmann
authors.affiliation: Department of Psychiatry, Unit for Research in Schizophrenia, Center for Psychiatric Neuroscience, Centre Hospitalier Universitaire Vaudois, Lausanne University Hospital (CHUV), University of Lausanne, Lausanne, Switzerland.
authors.forename: K Q
authors.initials: KQ
authors.lastname: Do
authors.affiliation: Department of Psychiatry, Service of General Psychiatry, Centre Hospitalier Universitaire Vaudois, Lausanne University Hospital (CHUV), Lausanne, Switzerland.
authors.forename: P
authors.initials: P
authors.lastname: Conus
mesh_terms: D000328:Adult; D016880:Anisotropy; D001714:Bipolar Disorder / Q000097:blood / Q000000981:diagnostic imaging / Q000473:pathology; D016022:Case-Control Studies; D003865:Major Depressive Disorder / Q000097:blood / Q000000981:diagnostic imaging / Q000473:pathology; D056324:Diffusion Tensor Imaging; D005260:Female; D020712:Fornix, Brain / Q000000981:diagnostic imaging* / Q000473:pathology; D005978:Glutathione / Q000097:blood; D005979:Glutathione Peroxidase / Q000097:blood; D006624:Hippocampus / Q000000981:diagnostic imaging* / Q000473:pathology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D009929:Organ Size; D018384:Oxidative Stress; D011618:Psychotic Disorders / Q000097:blood / Q000000981:diagnostic imaging* / Q000473:pathology; D012559:Schizophrenia / Q000097:blood / Q000000981:diagnostic imaging* / Q000473:pathology; D055815:Young Adult
chemical_list: D005979:Glutathione Peroxidase; D005978:Glutathione