Subtype-specific alterations of gamma-aminobutyric acid and glutamate in patients with major depression

Arch Gen Psychiatry. 2004 Jul;61(7):705-13. doi: 10.1001/archpsyc.61.7.705.


Background: Measurement of cortical gamma-aminobutyric acid (GABA) and glutamate concentrations is possible using proton magnetic resonance spectroscopy. An initial report, using this technique, suggested that occipital cortex GABA concentrations are reduced in patients with major depressive disorder (MDD) relative to healthy comparison subjects.

Objectives: To replicate the GABA findings in a larger sample of MDD patients, to examine the clinical correlates of the GABA reductions in these subjects, and to examine other critical metabolite levels.

Design: Study for association.

Setting: Academic clinical research program.

Participants: The GABA measurements were made on 38 healthy control subjects and 33 depressed subjects.

Interventions: Occipital cortex metabolite levels were measured using proton magnetic resonance spectroscopy.

Main outcome measures: The levels of occipital cortex GABA, glutamate, N-acetylaspartate, aspartate, creatine, and choline-containing compounds, along with several measures of tissue composition, were compared between the 2 groups.

Results: Depressed subjects had significantly lower occipital cortex GABA concentrations compared with healthy controls (P =.01). In addition, mean glutamate levels were significantly increased in depressed subjects compared with healthy controls (P<.001). Significant reductions in the percentage of solid tissue (P =.009) and the percentage of white matter (P =.04) in the voxel were also observed. An examination of a combined database including subjects from the original study suggests that GABA and glutamate concentrations differ among MDD subtypes.

Conclusions: The study replicates the findings of decreased GABA concentrations in the occipital cortex of subjects with MDD. It also demonstrates that there is a change in the ratio of excitatory-inhibitory neurotransmitter levels in the cortex of depressed subjects that may be related to altered brain function. Last, the combined data set suggests that magnetic resonance spectroscopy GABA measures may serve as a biological marker for a subtype of MDD.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aspartic Acid / analogs & derivatives*
  • Aspartic Acid / analysis
  • Aspartic Acid / metabolism
  • Choline / analysis
  • Choline / metabolism
  • Depressive Disorder / classification
  • Depressive Disorder / diagnosis
  • Depressive Disorder / metabolism*
  • Diagnostic and Statistical Manual of Mental Disorders
  • Female
  • Glutamic Acid / analysis
  • Glutamic Acid / metabolism*
  • Glutamine / analysis
  • Glutamine / metabolism
  • Humans
  • Magnetic Resonance Spectroscopy
  • Male
  • Middle Aged
  • Occipital Lobe / chemistry*
  • Occipital Lobe / metabolism
  • Psychiatric Status Rating Scales
  • Severity of Illness Index
  • gamma-Aminobutyric Acid / analysis
  • gamma-Aminobutyric Acid / metabolism*


  • Glutamine
  • Aspartic Acid
  • Glutamic Acid
  • gamma-Aminobutyric Acid
  • N-acetylaspartate
  • Choline