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Reduced Prefrontal Glutamate/Glutamine and  -Aminobutyric Acid Levels in Major Depression Determined Using Proton Magnetic Resonance Spectroscopy
Gregor Hasler, MD;
Jan Willem van der Veen, PhD;
Toni Tumonis, MS;
Noah Meyers, BS;
Jun Shen, PhD;
Wayne C. Drevets, MD
Arch Gen Psychiatry. 2007;64(2):193-200.
Context Increasing evidence indicates that major depressive disorder (MDD) is associated with altered function of the major excitatory and inhibitory neurotransmitters glutamate and  -aminobutyric acid (GABA), respectively. A recently developed magnetic resonance spectroscopy method allows for reliable measurement of glutamate/glutamine (Glx) and GABA concentrations in prefrontal brain regions that have been implicated in the pathophysiologic mechanisms of MDD by studies using other neuroimaging and postmortem techniques.
Objective To measure Glx and GABA levels in 2 regions of the prefrontal brain tissue in unmedicated adults with MDD.
Design Cross-sectional study for association.
Setting Psychiatric outpatient clinic.
Participants Twenty unmedicated, depressed patients with MDD and 20 age- and sex-matched controls.
Intervention Participants underwent scanning using a 3-T whole-body scanner with a transmit-receive head coil, providing a homogeneous radiofrequency field and the capability of obtaining spectroscopic measurements in a dorsomedial/dorsal anterolateral prefrontal region of interest (ROI) and a ventromedial prefrontal ROI.
Main Outcome Measures Glx and GABA levels derived from magnetic resonance spectroscopy signals.
Results Depressed patients had reduced Glx levels in both ROIs. The GABA levels were reduced in the dorsomedial/dorsal anterolateral prefrontal ROI. Levels of GABA and Glx were positively correlated in both ROIs.
Conclusions For the first time, GABA and Glx concentrations were compared between unmedicated depressed adults and controls in prefrontal ROIs. The abnormal reductions in Glx and GABA concentrations found in the MDD sample were compatible with findings from postmortem histopathologic studies, indicating that glial cell density is reduced in the same areas in MDD.
Author Affiliations: Department of Psychiatry, University Hospital, Zurich, Switzerland (Dr Hasler); and Magnetic Resonance Spectroscopy Core (Drs van der Veen and Shen) and Mood and Anxiety Disorders Program, Section on Neuroimaging in Mood and Anxiety Disorders (Ms Tumonis, Mr Meyers, and Dr Drevets), National Institute of Mental Health, National Institutes of Health, Bethesda, Md.
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