Reduced cortical gamma-aminobutyric acid levels in depressed patients determined by proton magnetic resonance spectroscopy

Background: Several lines of emerging evidence suggest that dysfunction of gamma-aminobutyric acid (GABA) systems is associated with major depression. However, investigation of this hypothesis is limited by difficulty obtaini ng noninvasive in vivo measures of brain GABA levels. In this study we used in vivo proton magnetic resonance spectroscopy to investigate the hypothes is that abnormalities in the GABA neurotransmitter system are associated wi th the neurobiologic processes of depression. Methods: The GABA levels were measured in the occipital cortex of medicatio n-free depressed patients meeting DSM-IV criteria (n = 14) and healthy cont rol subjects with no history of mental illness (n = 18) using a localized d ifference editing proton magneticresonance spectroscopy protocol. An analys is of covariance was employed to examine the effects of depression, sex, an d age. Results: The depressed patients demonstrated a highly significant (52%) red uction in occipital cortex GABA levels compared with the group of healthy s ubjects. While there were significant age and sex effects, there was no int eraction of diagnosis with either age or sex. Conclusion: This study provides the first evidence of abnormally low cortic al GABA concentrations in the brains of depressed patients.