title: Prefrontal GABA and glutathione imbalance in posttraumatic stress disorder: preliminary findings.
abstract: Although posttraumatic stress disorder (PTSD) is associated with a variety of structural and functional brain changes, the molecular pathophysiological mechanisms underlying these macroscopic alterations are unknown. Recent studies support the existence of an altered excitation-inhibition balance in PTSD. Further, there is preliminary evidence from blood-sample studies suggesting heightened oxidative stress in PTSD, potentially leading to neural damage through excessive brain levels of free radicals. In this study we investigated PTSD (n=12) and non-PTSD participants (n=17) using single-voxel proton magnetic resonance spectroscopy (MRS) in dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC). We found significantly higher levels of γ-amino butyric acid (GABA) (a primary inhibitory neurotransmitter) and glutathione (a marker for neuronal oxidative stress) in PTSD participants. Atypically high prefrontal inhibition as well as oxidative stress may be involved in the pathogenesis of PTSD.
authors.affiliation: Institute of Neuroradiology, University Hospital Zurich, Zurich, Switzerland. Electronic address: lars.michels@usz.ch.
authors.forename: Lars
authors.initials: L
authors.lastname: Michels
authors.affiliation: Department of Psychiatry and Psychotherapy, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schulte-Vels
authors.affiliation: Department of Psychiatry and Psychotherapy, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Matthis
authors.initials: M
authors.lastname: Schick
authors.affiliation: Center of MR-Research, University Children׳s Hospital Zurich, Zurich, Switzerland.
authors.forename: Ruth L
authors.initials: RL
authors.lastname: O'Gorman
authors.affiliation: Neural Systems Group, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Zeffiro
authors.affiliation: Psychiatric University Hospital, University of Bern, Bern, Switzerland.
authors.forename: Gregor
authors.initials: G
authors.lastname: Hasler
authors.affiliation: Department of Psychiatry and Psychotherapy, University Hospital Zurich, Zurich, Switzerland; Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Center of Education and Research (COEUR), Psychiatric Services of the County of St. Gallen-North, Wil, Switzerland.
authors.forename: Christoph
authors.initials: C
authors.lastname: Mueller-Pfeiffer
mesh_terms: D000328:Adult; D005260:Female; D005978:Glutathione / Q000378:metabolism*; D006179:Gyrus Cinguli / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D017397:Prefrontal Cortex / Q000378:metabolism*; D066244:Proton Magnetic Resonance Spectroscopy; D013313:Stress Disorders, Post-Traumatic / Q000378:metabolism*; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D005680:gamma-Aminobutyric Acid; D005978:Glutathione
keywords: Anterior cingulate cortex; Dorsolateral prefrontal cortex; Gamma-amino-butyric acid (GABA); N-acetyl aspartate (NAA); Proton magnetic resonance spectroscopy