Hippocampal N-acetylaspartate Levels Before Trauma Predict the Development of Long-Lasting Posttraumatic Stress Disorder-like Symptoms in Mice

Abstract

Only a certain proportion of individuals develop posttraumatic stress disorder (PTSD) in the aftermath of a trauma. Biomarkers of individual susceptibility are not yet known but would enable selected primary and secondary prevention of PTSD. Hippocampal N-acetylaspartate (NAA) levels were assessed by proton magnetic resonance spectroscopy ((1)H-MRS) in C57BL/6N mice prior to the perception of a 1.5 mA electric footshock. Associative (freezing to trauma context) and nonassociative (freezing to a neutral tone; i.e., hyperarousal) symptoms of PTSD-like fear were assessed 4, 5, 18, and 32 weeks after trauma. Low NAA levels in the left dorsal hippocampus predicted persistent PTSD-like symptoms (both contextual freezing and hyperarousal), while animals with pretraumatic high levels of NAA decreased their fear reactions to control levels in consequence of re-exposure to associative and nonassociative cues. N-AA levels in the right dorsal hippocampus, in contrast, were only partially predictive of the individual susceptibility to develop PTSD-like symptoms. Left hippocampal NAA levels might be a predictor of an increased susceptibility to develop PTSD after trauma.