Measurement of cortical γ-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.
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.
Study for association.
Academic clinical research program.
The GABA measurements were made on 38 healthy control subjects and 33
Occipital cortex metabolite levels were measured using proton magnetic
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
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.
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.