Increased rostral medial frontal GABA+ in early psychosis is obscured by levels of negative affect

Abstract

ABSTRACTBackgroundEvidence suggests dysfunction of GABAergic interneurons in psychosis, and prior research has linked GABAergic function with a tendency toward negative affective states. Magnetic resonance spectroscopy (MRS) studies measuring GABA have yielded inconsistent findings. We investigate GABA concentrations in young adults with attenuated psychosis syndrome (APS) and first episode psychosis (FEP), as well as testing the hypothesis that negative affect is a clinical phenotype that is associated with reduced GABA.MaterialsMRS data were obtained from 14 patients with FEP, 7 patients with APS and 15 healthy controls (HC), using a MEGA-PRESS sequence on a 3T Philips Ingenia scanner. Voxels were placed in rostral MFC and midline-occipital cortex. Gannet 3.1 was used to determine GABA+ and Glx (glutamate and glutamine combined) concentrations.ResultsWe found a trend towards increased rostral MFC GABA+ concentrations in FEP, but no group differences in occipital GABA+ concentrations. When covarying for scores on the Psychological Stress Index, rostral MFC GABA+ levels in FEP were significantly greater than APS and HC. Planned comparisons revealed a trend towards increased rostral MFC GABA+ in APS relative to HC. No group differences in Glx or occipital GABA+ were found.ConclusionThese results, considered alongside previously published findings, suggest multiple factors influencing GABA+ in psychosis. We conclude a process exists which drives up GABA+ in early psychosis, alongside a separate process in which reduced GABA+ is associated with increased negative affect. These multiple processes have resulted in contradictory findings, and their untangling is critical to understanding of GABA+ in psychosis.