title: Hippocampus Glutamate and N-Acetyl Aspartate Markers of Excitotoxic Neuronal Compromise in Posttraumatic Stress Disorder.
abstract: Hippocampus atrophy is implicated in posttraumatic stress disorder (PTSD), and may partly reflect stress-induced glutamate excitotoxicity that culminates in neuron injury and manifests as re-experiencing symptoms and other memory abnormalities. This study used high-field proton magnetic resonance spectroscopy (MRS) to determine whether PTSD is associated with lower hippocampus levels of the neuron marker N-acetyl aspartate (NAA), along with higher levels of glutamate (Glu) and Glu/NAA. We also predicted that metabolite levels would correlate with re-experiencing symptoms and lifetime trauma load. Twenty-four adult PTSD patients and 23 trauma-exposed normal controls (TENC) underwent 4T MRS of the left and right hippocampus. Participants received psychiatric interviews, and completed the Traumatic Life Events Questionnaire to define lifetime trauma load. Relative to TENC participants, PTSD patients exhibited significantly lower NAA in right and left hippocampi, and significantly higher Glu and Glu/NAA in the right hippocampus. Re-experiencing symptoms were negatively correlated with left and right NAA, and positively correlated with right Glu and right Glu/NAA. Trauma load was positively correlated with right Glu/NAA in PTSD patients. When re-experiencing symptoms and trauma load were examined together in relation to right Glu/NAA, only re-experiencing symptoms remained a significant correlate. This represents the first report that PTSD is associated with MRS markers of hippocampus Glu excess, together with indices of compromised neuron integrity. Their robust associations with re-experiencing symptoms affirm that MRS indices of hippocampus neuron integrity and glutamate metabolism may reflect biomarkers of clinically significant disease variation in PTSD.
authors.affiliation: Center for Depression, Anxiety and Stress Research, McLean Hospital, Belmont, MA, USA.|Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
authors.forename: Isabelle M
authors.initials: IM
authors.lastname: Rosso
authors.affiliation: Center for Depression, Anxiety and Stress Research, McLean Hospital, Belmont, MA, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Crowley
authors.affiliation: Department of Psychiatry, Harvard Medical School, Boston, MA, USA.|McLean Imaging Center, McLean Hospital, Belmont, MA, USA.
authors.forename: Marisa M
authors.initials: MM
authors.lastname: Silveri
authors.affiliation: Center for Depression, Anxiety and Stress Research, McLean Hospital, Belmont, MA, USA.|Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
authors.forename: Scott L
authors.initials: SL
authors.lastname: Rauch
authors.affiliation: Department of Psychiatry, Harvard Medical School, Boston, MA, USA.|McLean Imaging Center, McLean Hospital, Belmont, MA, USA.
authors.forename: J Eric
authors.initials: JE
authors.lastname: Jensen
mesh_terms: D000328:Adult; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D015415:Biomarkers; D016022:Case-Control Studies; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D066244:Proton Magnetic Resonance Spectroscopy; D013313:Stress Disorders, Post-Traumatic / Q000378:metabolism*; D014947:Wounds and Injuries / Q000378:metabolism; D055815:Young Adult
chemical_list: D015415:Biomarkers; D001224:Aspartic Acid; D018698:Glutamic Acid; C000179:N-acetylaspartate