Medial Frontal Cortex GABA Concentrations in Psychosis Spectrum and Mood Disorders: A Meta-analysis of Proton Magnetic Resonance Spectroscopy Studies

Abstract

BackgroundAbnormalities of GABAergic (gamma-aminobutyric acidergic) systems may play a role in schizophrenia and mood disorders. Magnetic resonance spectroscopy allows for noninvasive in vivo quantification of GABA; however, studies of GABA in schizophrenia have yielded inconsistent findings. This may stem from grouping together disparate voxels from functionally heterogeneous regions. MethodsWe searched PubMed for magnetic resonance spectroscopy studies of GABA in the medial frontal cortex (MFC) in patients with schizophrenia, bipolar disorder, and depression and in individuals meeting criteria for ultra-high risk for psychosis. Voxel placements were classified as rostral-, rostral-mid-, mid-, or posterior MFC, and meta-analyses were conducted for each group for each subregion. ResultsOf 341 screened articles, 23 studies of schizophrenia, 6 studies of bipolar disorder, 20 studies of depression, and 7 studies of ultra-high risk met the inclusion criteria. Meta-analysis revealed lower mid- (standardized mean difference [SMD] = −0.28, 95% 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 schizophrenia and increased rostral MFC 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. We found no evidence for GABA differences in individuals at ultra-high risk for psychosis. ConclusionsWhile limited by small numbers of published studies, these results substantiate the relevance of GABA in the pathophysiology of psychosis spectrum and mood disorders and underline the importance of voxel placement.