• Online Features  This Article  • Full text  • PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on Web of Science (131)  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Topic Collections  • Neurology  • Neuroimaging  • Neurology, Other  • Psychiatry  • Depression  • Psychiatry, Other  • Alert me on articles by topic  Social Bookmarking   What's this?

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.

CiteULike    Connotea    Delicious    Digg    Facebook    Reddit    Technorati    Twitter     What's this?

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Anterior Cingulate Cortex {gamma}-Aminobutyric Acid in Depressed Adolescents: Relationship to Anhedonia
Gabbay et al.
Arch Gen Psychiatry 2012;69:139-149.
ABSTRACT | FULL TEXT  

Elevated Prefrontal Cortex {gamma}-Aminobutyric Acid and Glutamate-Glutamine Levels in Schizophrenia Measured In Vivo With Proton Magnetic Resonance Spectroscopy
Kegeles et al.
Arch Gen Psychiatry 2012;0:archgenpsychiatry.2011.15-11.
ABSTRACT | FULL TEXT  

Genetic Association of ErbB4 and Human Cortical GABA Levels In Vivo
Marenco et al.
J. Neurosci. 2011;31:11628-11632.
ABSTRACT | FULL TEXT  

Corticotropin-Releasing Hormone, Glutamate, and {gamma}-Aminobutyric Acid in Depression
Gao and Bao
Neuroscientist 2011;17:124-144.
ABSTRACT  

Effect of Acamprosate on Magnetic Resonance Spectroscopy Measures of Central Glutamate in Detoxified Alcohol-Dependent Individuals: A Randomized Controlled Experimental Medicine Study
Umhau et al.
Arch Gen Psychiatry 2010;67:1069-1077.
ABSTRACT | FULL TEXT  

Lack of effect of citalopram on magnetic resonance spectroscopy measures of glutamate and glutamine in frontal cortex of healthy volunteers
Taylor et al.
J Psychopharmacol 2010;24:1217-1221.
ABSTRACT  

Long-term anxiolytic and antidepressant-like behavioural effects of tiagabine, a selective GABA transporter-1 (GAT-1) inhibitor, coincide with a decrease in HPA system activity in C57BL/6 mice
Thoeringer et al.
J Psychopharmacol 2010;24:733-743.
ABSTRACT  

The Role of the Tripartite Glutamatergic Synapse in the Pathophysiology and Therapeutics of Mood Disorders
Machado-Vieira et al.
Neuroscientist 2009;15:525-539.
ABSTRACT  

Physical Characteristics of the Menstrual Cycle and Premenstrual Depressive Symptoms
Kiesner
Psychological Science 2009;20:763-770.
ABSTRACT | FULL TEXT  

The Relationship Between Aberrant Neuronal Activation in the Pregenual Anterior Cingulate, Altered Glutamatergic Metabolism, and Anhedonia in Major Depression
Walter et al.
Arch Gen Psychiatry 2009;66:478-486.
ABSTRACT | FULL TEXT  

Depressive Disorders: Focally Altered Cerebral Perfusion Measured with Arterial Spin-labeling MR Imaging1
Lui et al.
Radiology 2009;251:476-484.
ABSTRACT | FULL TEXT  

Alcoholism: A Systems Approach From Molecular Physiology to Addictive Behavior
Spanagel
Physiol. Rev. 2009;89:649-705.
ABSTRACT | FULL TEXT  

Neurobiological mechanisms in major depressive disorder
aan het Rot et al.
CMAJ 2009;180:305-313.
FULL TEXT  

Alternative Splicing, Methylation State, and Expression Profile of Tropomyosin-Related Kinase B in the Frontal Cortex of Suicide Completers
Ernst et al.
Arch Gen Psychiatry 2009;66:22-32.
ABSTRACT | FULL TEXT  

Combined Neuroimaging, Neurocognitive and Psychiatric Factors to Predict Alcohol Consumption Following Treatment for Alcohol Dependence
Durazzo et al.
Alcohol Alcohol 2008;43:683-691.
ABSTRACT | FULL TEXT  

Differential effects of citalopram and reboxetine on cortical Glx measured with proton MR spectroscopy
Taylor et al.
J Psychopharmacol 2008;22:473-476.
ABSTRACT