Elevated Prefrontal Cortex γ-Aminobutyric Acid and Glutamate-Glutamine Levels in Schizophrenia Measured In Vivo With Proton Magnetic Resonance Spectroscopy

Abstract

To our knowledge, this study presents the first GABA concentration measurements in unmedicated patients with schizophrenia, who showed elevations in both GABA and Glx levels in the medial prefrontal cortex but not the dorsolateral prefrontal cortex. Medicated patients did not show these elevations, suggesting possible normalization of levels with antipsychotic medication. The Glx elevations agree with prior magnetic resonance spectroscopy literature, but GABA elevations were unexpected and suggest possible involvement of classes of interneurons not found to show impairments in postmortem studies.

GABA and glutamate in schizophrenia: A 7 T 1H-MRS study

“…However, we found an inverse correlation between GABA/Cr ratios and glutamate levels in the parieto-occipital cortex in healthy controls but not in patients. Considering the tight coupling of GABA and glutamate through GAD, this is unexpected and contrasts with previous studies reporting positive correlations between GABA and glutamate in patients in the anterior cingulate and parieto-occipital cortices (Ongür et al, 2010) and in a mixed sample of patients and healthy controls in the prefrontal cortex (Kegeles et al, 2012). …”

“…Indeed, pharmacologically induced NMDA receptor hypofunction causes increases in glutamate levels (Moghaddam et al, 1997). Also, a longitudinal study (De la Fuente-Sandoval et al, 2013) and a cross-sectional study (Kegeles et al, 2012) showed that antipsychotic medication decreases the elevated glutamate levels in the unmedicated state. Altered glutamate levels may be a result of hypofunction of the NMDA-type of glutamate receptor (Olney et al, 1999; Kondziella et al, 2007; Stone et al, 2009).…”

“…So far, a total of seven studies investigated GABA levels in vivo in the brains of patients with schizophrenia, using proton MRS ( 1 H -) (Kegeles et al, 2012; De la Fuente-Sandoval et al, 2011; Goto et al, 2009; Ongür et al, 2010; Tayoshi et al, 2010; Yoon et al, 2010; Rowland et al, 2013), which reported increased (Kegeles et al, 2012; Ongür et al, 2010), decreased (Goto et al, 2009; Yoon et al, 2010), and normal (Kegeles et al, 2012; Goto et al, 2009; Tayoshi et al, 2010; Yoon et al, 2010; Rowland et al, 2013) GABA levels dependent on disease stage, medication intake and brain area studied. The only study of GABA in unmedicated patients found elevated GABA levels in the medial prefrontal cortex in unmedicated patients, but not in medicated patients, suggesting that antipsychotic medication decreases the elevated GABA levels (Kegeles et al, 2012).…”

“…The only study of GABA in unmedicated patients found elevated GABA levels in the medial prefrontal cortex in unmedicated patients, but not in medicated patients, suggesting that antipsychotic medication decreases the elevated GABA levels (Kegeles et al, 2012). However, since these studies have been done at conventional magnetic field strengths (such as 3 T) subtle changes in these metabolite levels may have remained concealed.…”

Developing Synaesthesia

“…That is, it may be the case that this measure does not constitute a sufficiently stringent test of the prediction of reduced GABA in synaesthesia. For example, one reason to doubt the link between GABA and PS/OS ratios in the Yoon et al (2010) study is that patients with schizophrenia were medicated, which may represent an important confound in the measurement of GABA levels in this population (Kegeles et al, 2012). However, it is readily evident that the relationship between GABA and the PS/OS ratio in Yoon et al (2010) is driven by controls, rather than schizophrenics.…”