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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.

Hippocampus Glutamate and N-Acetyl Aspartate Markers of Excitotoxic Neuronal Compromise in Posttraumatic Stress Disorder