N-acetylaspartylglutamate (NAAG) and N-acetylaspartate (NAA) in patients with schizophrenia

Abstract

Background: Imbalance of glutamatergic neurotransmission has been proposed as a key mechanism underlying symptoms of schizophrenia. The neuropetide N-acetylaspartylglutamate (NAAG) modulates glutamate release. NAAG provides a component of the proton magnetic resonance spectrum (1H-MRS) in humans. The signal of NAAG, however, largely overlaps with its precursor and degrading product N-acetylaspartate (NAA) that by itself does not act in glutamatergic neurotransmission. Methods: We quantified NAAG and NAA separately from the 1H-MRS signal in 20 patients with schizophrenia and 20 healthy comparison subjects on a 3.0 Tesla MR scanner. The 1H-MRS voxels were positioned in the anterior cingulate cortex (ACC) and in the left frontal lobe. Psychopathological symptoms and cognitive performance were assessed. Results: In the ACC, the ratio NAAG/NAA was increased (P =. 041) and NAAG was increased at a trend level (P =. 066) in patients, while NAA was reduced (P =. 030). NAA correlated with attention performance in patients (r =. 64, P =. 005) in the ACC. There was no group difference of NAAG, NAA, or NAAG/NAA in the frontal lobe but an inverse correlation of NAAG with negatives symptoms (Positive and Negative Symptoms Scale [PANSS] negative, r =-.58, P =. 018) and with the total symptom score (PANSS total, r =-.50, P =. 049). In addition, there was a positive correlation of frontal lobe NAAG (r =. 53, P =. 035) and NAAG/NAA (r =. 54, P =. 030) with episodic memory in patients. Conclusions: In this study, we present the first in vivo evidence for altered NAAG concentration in patients with schizophrenia. © 2011 The Author.