The impact of matching for reproductive status on the comparison of magnetic spectroscopic measurements of glutamate and gamma-aminobutyric acid plus in the medial prefrontal cortex of women with major depression

Objectives: The role played by medial prefrontal cortex (MPFC) glutamate (Glu) and gamma-aminobutyric acid (GABA) in the pathophysiology and the treatment of major depression (MD) is increasingly recognized. Although measurements of MPFC GABA and Glu have been shown to be sensitive to physiological fluctuations of female hormones, none of the magnetic resonance spectroscopy (MRS) investigations of MPFC Glu and GABA in MD have controlled for possible bias effect of the reproductive stage of the women included. Methods: MPFC Glu and GABA+ (which include homocarnosine and macromolecules) referenced to creatine and phosphocreatine, were measured via magnetic resonance spectroscopy (MRS) using a 3-Tesla magnet in 24 women with MD and 24 healthy women paired for reproductive status. All participants were unmedicated. Results: There were no statistical differences in either MPFC Glu [95 % CI: (-0.025, 0.034)1 or MPFC GABA+ [95 % CI: (-0.005, 0.017)1 between women with MD and healthy controls. Conclusions: Our investigation does not support abnormalities in measurement of MPFC Glu and GABA in MD women when stringent control for reproductive status is performed. As a result of the inherent limitations of MRS methodology, our results do not preclude glutamatergic and GABAergic dysregulations in the MPFC of women with MD.