Effect of Acute Psychological Stress on Prefrontal GABA Concentration Determined by Proton Magnetic Resonance Spectroscopy

Abstract

Objective Impaired function of the central gamma-aminobutyric acid (GABA) system, which provides the brain’s major inhibitory pathways, is thought to play an important role in the pathophysiology of anxiety disorders. The effect of acute psychological stress on the human GABA-ergic system is still unknown, however. The purpose of this study was to determine the effect of acute stress on prefrontal GABA levels. Method A recently developed noninvasive magnetic resonance spectroscopy method was used to measure changes in the GABA concentration of the prefrontal cortex in 10 healthy human subjects during a threat-of-shock condition and during a safe condition (two sessions on different days). The main outcome measure was the mean GABA concentration within a 3×3×2-cm3 voxel selected from the medial prefrontal cortex. Results Prefrontal GABA decreased by approximately 18% in the threat-of-shock condition relative to the safe condition. This reduction was specific to GABA, since the concentrations of N-acetyl-aspartate, choline-containing compounds, and glutamate/glutamine levels obtained in the same spectra did not change significantly. Conclusions This result appeared compatible with evidence from preclinical studies in rodents, which showed rapid presynaptic down-regulation of GABA-ergic neurotransmission in response to acute psychological stress. The molecular mechanism and functional significance of this reduced inhibitory effect of acute psychological stress in relation to impaired GABA-ergic function in anxiety disorders merit further investigation.

Investigation of Cortical Glutamate–Glutamine and γ-Aminobutyric Acid in Obsessive–Compulsive Disorder by Proton Magnetic Resonance Spectroscopy

“…Reduced MPFC inhibitory tone is also consistent with current OCD models that posit abnormal frontostriatal activation (Maia et al, 2008;Pittenger et al, 2011;Ting and Feng, 2011;Wu et al, 2012), as reduced MPFC inhibitory tone could generate abnormal striatal activation either directly due to ACC projections to the striatum or indirectly due to ACC projections to the OFC (Price and Drevets, 2010;Schmahmann and Pandya, 2006). On the other hand, acute psychological stress has recently been shown to decrease MPFC GABA levels in healthy controls (Hasler et al, 2010). Therefore, reduced MPFC GABA levels may not lead to OCD symptoms per se but simply reflect the emotional and stressed state of these patients.…”

“…Neither was the case in our OCD sample. Disruption of the normal positive correlation between GABA and Glx has previously been reported under conditions of abnormal GABA levels (Hasler et al, 2010;Sanacora et al, 2004;Yang and Shen, 2009).…”

Activation of GABAA receptors in the medial prefrontal cortex produces an anxiolytic-like response

“…GABAergic neurons are one of the most important components prevalent in all areas of the brain and its neurotransmission is vital for brain function (5). Although GABA plays a major role in the modulation of virtually all cognitive and behavioural processes, several basic and clinical studies have particularly highlighted the role of this neurotransmitter in the central modulation of anxiety and stress responses (6)(7)(8)(9).…”

GABAergic Influence in the Antidepressant Effect of Fluoxetine in Unstressed and Stressed Mice

“…GABAergic transmission is highly sensitive to stressful situations (Orchinik et al, 2001;Caldji et al, 2004;Maggio and Segal, 2009;Surget et al, 2008); the fact is supported by the fact that the psychological stress induces presynaptic down-regulation of prefrontal GABAergic neurotransmission (Hasler et al, 2010).…”