Medial Frontal Cortex Gamma-Aminobutyric Acid Concentrations in Psychosis and Mood Disorders: A Meta-Analysis of Proton Magnetic Resonance Spectroscopy Studies

Abstract

Background: Abnormalities of gamma-aminobutyric acid-ergic (GABAegic) systems may play an important role in psychosis spectrum and mood disorders. Proton magnetic resonance spectroscopy allows for non-invasive in vivo quantification of GABA; however, studies of GABA in psychosis have yielded inconsistent findings. This may stem from grouping together disparate voxels from functionally heterogeneous regions. Methods: We searched the PubMed database for magnetic resonance spectroscopy studies of medial frontal cortex (MFC) GABA in patients with psychosis, bipolar disorder, depression, and individuals meeting ultra-high risk for psychosis criteria. Voxel placements were classified as rostral-, rostral-mid-, mid-, or posterior MFC, and random effects meta-analyses conducted for each group, for each MFC sub-region. Results: Of 341 screened articles, 23 studies of psychosis (752 patients,856 controls), 6 studies of bipolar disorder (129 patients, 94 controls), 20 studies of depression (463 cases, 449 controls) and 7 studies of ultra-high risk (229 patients, 232 controls) met inclusion criteria. Meta-analysis revealed lower mid- (SMD = -0.28, 95% confidence interval [CI] = -0.48 to -0.07, p < .01) and posterior (SMD = -0.29, 95% CI = -0.49 to -0.09, p <.01) MFC GABA in psychosis, and increased rostral GABA in bipolar disorder (SMD = 0.76, 95% CI = 0.25 to 1.25, p < .01). In depression, reduced rostral MFC GABA (SMD = -0.36, 95% CI = -0.64 to -0.08, p = .01) did not survive correction for multiple comparisons. Conclusions: These results substantiate the relevance in the ethology of psychosis spectrum and mood disorders and underline the importance of voxel placement.