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Reduced Cortical -Aminobutyric Acid Levels in Depressed Patients Determined by Proton Magnetic Resonance Spectroscopy

Gerard Sanacora, MD, PhD; Graeme F. Mason, PhD; Douglas L. Rothman, PhD; Kevin L. Behar, PhD; Fahmeed Hyder, PhD; Ognen A. C. Petroff, MD; Robert M. Berman, MD; Dennis S. Charney, MD; John H. Krystal, MD

Arch Gen Psychiatry. 1999;56:1043-1047.

Background  Several lines of emerging evidence suggest that dysfunction of -aminobutyric acid (GABA) systems is associated with major depression. However, investigation of this hypothesis is limited by difficulty obtaining noninvasive in vivo measures of brain GABA levels. In this study we used in vivo proton magnetic resonance spectroscopy to investigate the hypothesis that abnormalities in the GABA neurotransmitter system are associated with the neurobiologic processes of depression.

Methods  The GABA levels were measured in the occipital cortex of medication-free depressed patients meeting DSM-IV criteria (n=14) and healthy control subjects with no history of mental illness (n=18) using a localized difference editing proton magnetic resonance spectroscopy protocol. An analysis of covariance was employed to examine the effects of depression, sex, and age.

Results  The depressed patients demonstrated a highly significant (52%) reduction in occipital cortex GABA levels compared with the group of healthy subjects. While there were significant age and sex effects, there was no interaction of diagnosis with either age or sex.

Conclusion  This study provides the first evidence of abnormally low cortical GABA concentrations in the brains of depressed patients.

From the Departments of Psychiatry (Drs Sanacora, Mason, Berman, Charney, and Krystal), Biomedical Engineering (Dr Mason), Radiology (Dr Rothman), Neurology (Drs Behar and Petroff), and Molecular Biophysics and Biochemistry (Dr Hyder), Yale University School of Medicine, New Haven, Conn.

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