303. Measurement of human cortical GABA synthesis in vivo

Abstract

Studies of GABA receptors and CSF GABA levels have implicated the GABAergic system in mood disorders. Recently H magnetic resonance spectroscopy (MRS) has shown that cortical GABA is changed in unipolar depression. The mechanism of the changes is unknown and may hold clues for clinical effects and treatments. GABA synthesis may be reduced, or GABA turnover may be elevated by GABAergic overstimulation, reaching new, lower steady-state levels. Key to evaluating these possibilities is the ability to measure the synthesis of cortical GABA in humans in vivo. C MRS was used to detect the incorporation of the non-radioactive isotope C in GABA, glutamate, and glutamate during a 90-minute infusion of [1-C]glucose in three healthy volunteers. The GABA C2 time course was fitted with a single exponential function after removing the contribution from natural abundance labeling of the co-resonant N-acetylaspartate C3, showing that 2.4 6 2.1% (mean 6 s.d.) of the GABA pool is degraded and replaced per minute. Given a GABA concentration of 1.48 mmol g in healthy controls obtained from previous H MRS studies (Sanacora et al., Arch Psych 56:1043), the rate of synthesis of GABA was estimated to be 0.035 mmol min g, which is ;4% of the rate of the cortical tricarboxylic acid cycle. While more studies will more precisely define the rate, the results demonstrate the possibility of direct measurements of GABA synthesis in mood disorders.