Spectroscopic markers of memory impairment, symptom severity and age of onset in older people with lifetime depression: Discrete roles of N-acetyl aspartate and glutamate

J Affect Disord. 2015 Sep 1;183:31-8. doi: 10.1016/j.jad.2015.04.023. Epub 2015 Apr 22.


Background: Glutamate (Glu) and N-acetyl aspartate (NAA) are markers of excitatory processes and neuronal compromise respectively. Increased Glu and decreased NAA concentrations have been implicated in the pathophysiology of depression and cognitive impairment respectively.

Objective: To determine the relationship between NAA, Glu, memory and key clinical features in older people with lifetime depression compared to comparison subjects.

Method: Thirty-five health-seeking older adults (mean age=63.57 years), with a lifetime depression diagnosis, and 21 age-matched healthy comparison subjects (mean age=65.48 years) underwent neuropsychological testing, psychiatric assessment and proton magnetic resonance spectroscopy from which Glu and NAA were measured (reported as a ratio to creatine).

Results: Compared to comparison subjects, the depressed subjects showed poorer verbal learning and memory retention. Hippocampal NAA and Glu did not differ significantly between groups. However, in comparison subjects, lower levels of hippocampal Glu were associated with poorer memory retention (r=0.55, p=0.018). In the depressed subjects, lower levels of hippocampal NAA were related to poorer verbal learning (r=0.44, p=0.008) and memory retention (r=0.41, p=0.018). Greater hippocampal Glu was associated with more severe depressive symptoms (r=0.35, p=0.039) and an earlier age of illness onset (r=-0.37, p=0.031).

Limitations: This is a cross sectional study with a heterogeneous group of depressed subjects.

Conclusion: Our findings highlight that hippocampal neurometabolites are entwined with both clinical and cognitive features associated with depression in older adults and further suggest that differential mechanisms may underpin these features.

Keywords: Depression; Glutamate; Magnetic resonance spectroscopy; Memory impairment; N-acetyl aspartate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aspartic Acid / analogs & derivatives*
  • Aspartic Acid / metabolism
  • Case-Control Studies
  • Cross-Sectional Studies
  • Depression / diagnosis
  • Depression / metabolism*
  • Female
  • Glutamic Acid / metabolism*
  • Humans
  • Magnetic Resonance Spectroscopy / methods
  • Male
  • Memory Disorders / diagnosis
  • Memory Disorders / metabolism*
  • Middle Aged
  • Neuropsychological Tests
  • Prefrontal Cortex / metabolism*


  • Aspartic Acid
  • Glutamic Acid
  • N-acetylaspartate