A pilot study of hippocampal N-acetyl-aspartate in youth with treatment resistant major depression

•N-acetyl-aspartate is thought to be a marker of neuronal health/viability.•Reduced N-acetyl-aspartate was found in the hippocampus in youth with depression.•Changes in N-acetyl-aspartate may be related to glutamate neurotransmission.

BackgroundSmaller hippocampal volumes, as assessed by magnetic resonance imaging (MRI), and proton magnetic resonance spectroscopy (1H-MRS) indexed alterations in brain metabolites have been identified in adults with major depressive disorder (MDD). Our group has found similar effects in MDD youth. However, this has not been studied in youth with treatment resistant MDD (TRD), nor has the interaction between regional N-acetyl-aspartate and volume deficits. N-acetyl-aspartate is an amino acid in the synthesis pathway of glutamate, and serves a marker of neuronal viability/number.MethodsFifteen typically developing youth (16-22 years of age; 7 males, 8 females) and eighteen youth with TRD (14-22 years of age; 8 males, 10 females) underwent 1H-MRS and MRI on a 3 T scanner. A short echo PRESS protocol was used with voxels in the right and left hippocampi (6 mL each). Hippocampal volume was evaluated using FreeSurfer.ResultsCompared with the typically developing group, youth with TRD had lower concentrations of N-acetyl-aspartate in the left hippocampus (p=0.004), and a trend for smaller left hippocampal volume (p=0.067). In TRD subjects, hippocampal N-acetyl-aspartate was inversely correlated with left (r=−0.68, p=0.003) but not right hippocampal volume. Right hippocampal glutamate+glutamine was greater in TRD youth compared to typically developing controls (p=0.007).ConclusionsThese results suggest a neurochemical and structural deficit in the hippocampi of youth with TRD. These findings fit with the role of N-acetyl-aspartate in glutamate neurotransmission and the effect of glutamate on brain morphology.